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Sample records for interleukin-8

  1. Shear stress and interleukin-8 (IL-8) on the proliferation ...

    African Journals Online (AJOL)

    Endothelial progenitor cells (EPCs) derived from bone marrow, are also found in circulation and involved in both tumor vasculogenesis and wound healing. During the process of EPCs incorporation into tissues and neovascularization, the cells are exposed to fluid shear stress. Interleukin-8 (IL-8) has been shown to play an ...

  2. Evaluation of Interleukin 8 gene polymorphism for predicting ...

    African Journals Online (AJOL)

    Background and aim: Previous studies have observed the association between inflammation and chronic kidney disease (CKD). The role played by Interleukin 8 (IL8) gene polymorphism has not been studied yet. Hence, the present study has been designed as the first attempt to identify the possible associations between ...

  3. Western Analysis of Intracellular Interleukin-8 in Human Mononuclear Leukocytes

    OpenAIRE

    Miskolci, Veronika; Hodgson, Louis; Cox, Dianne; Vancurova, Ivana

    2014-01-01

    Most cytokines are stored in the cytoplasm until their release into the extracellular environment; however, some cytokines have been reported to localize in the nucleus. Traditional whole cell extract preparation does not provide information about the intracellular localization of cytokines. Here, we describe how to prepare cytoplasmic and nuclear extracts that can be analyzed by immunoblotting. While in this chapter we use this method to analyze intracellular localization of interleukin-8 (I...

  4. Immunohistochemical detection of interleukin-8 in inflamed porcine tissues

    DEFF Research Database (Denmark)

    Laursen, Henriette; Jensen, Henrik Elkær; Leifsson, Páll S.

    2014-01-01

    The objective of this study was to identify the specific localization of interleukin-8 (IL-8) in cells in situ in a variety of inflammatory processes in different tissues from pigs. Our hypothesis was that IL-8 primarily is a neutrophil related cytokine present in all extravascular neutrophils...... while expression also occurs in other cell types in response to an inflammatory stimulus. Using IL-8 immunohistochemistry we discovered that neutrophils were the predominant IL-8 positive cell population while epithelial cell types and endothelium of postcapillary venules could be positive when situated...... in close vicinity of an inflammatory lesion. Furthermore, endothelial cells of newly formed vessels in granulation tissue were positive in some specimens. Some sub-populations of inflammatory neutrophils were, however, IL-8 negative which could reflect some phase of neutrophil swarming....

  5. [Acute inflammation phase reactants and interleukin-8 in myocardial infarction].

    Science.gov (United States)

    Zorin, N A; Podkhomutnikov, V M; Iankin, M Iu; Zorina, V N; Arkhipova, S V; Riabicheva, T G

    2009-04-01

    The study was undertaken to search for additional diagnostic criteria allowing the depth of myocardial damage to be estimated in males aged 57.2 +/- 9.6 years. Few interrelated acute phase reaction indices, including the levels of interleukin-8 (IL-8), lactoferrin (LF), alpha2-macroglobulin (alpha2-MG), plasmin (PL) and alpha2-MG-PL circulating complexes, were studied in serum on days 1, 7, and 17 of the onset of the disease. In small-focal myocardial infarction, the levels of alpha2-MG and PL were decreased on day 1 and those of LF and IL-8 were increased on day 14. On the contrary, in large-focal myocardial infarction, the concentrations of IL-8 and LF rose just on day 1 while those of alpha2-MG and PL remained unchanged. The detected differences may be used as additional criteria in differential diagnosis, particularly when ECG was of no informative value. Further, the concurrent elevation of alpha2-MG, PL, and PL-alpha2MG concentrations in large-focal myocardial infarction is indicative of poor prognosis.

  6. Characterization of interleukin-8 receptors in non-human primates

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, V.; Coto, E.; Gonzalez-Roces, S.; Lopez-Larrea, C. [Hospital Central de Asturias, Oviedo (Spain)] [and others

    1996-09-01

    Interleukin-8 is a chemokine with a potent neutrophil chemoatractant activity. In humans, two different cDNAs encoding human IL8 receptors designated IL8RA and IL8RB have been cloned. IL8RA binds IL8, while IL8RB binds IL8 as well as other {alpha}-chemokines. Both human IL8Rs are encoded by two genes physically linked on chromosome 2. The IL8RA and IL8RB genes have open reading frames (ORF) lacking introns. By direct sequencing of the polymerase chain reaction products, we sequenced the IL8R genes of cell lines from four non-human primates: chimpanzee, gorilla, orangutan, and macaca. The IL8RB encodes an ORF in the four non-human primates, showing 95%-99% similarity to the human IL8RB sequence. The IL8RA homologue in gorilla and chimpanzee consisted of two ORF 98%-99% identical to the human sequence. The macaca and orangutan IL8RA homologues are pseudogenes: a 2 base pair insertion generated a sequence with several stop codons. In addition, we describe the physical linkage of these genes in the four non-human primates and discuss the evolutionary implications of these findings. 25 refs., 5 figs., 3 tabs.

  7. Giardia duodenalis cathepsin B proteases degrade intestinal epithelial interleukin-8 and attenuate interleukin-8-induced neutrophil chemotaxis.

    Science.gov (United States)

    Cotton, James A; Bhargava, Amol; Ferraz, Jose G; Yates, Robin M; Beck, Paul L; Buret, Andre G

    2014-07-01

    Giardia duodenalis (syn. G. intestinalis, G. lamblia) infections are a leading cause of waterborne diarrheal disease that can also result in the development of postinfectious functional gastrointestinal disorders via mechanisms that remain unclear. Parasite numbers exceed 10(6) trophozoites per centimeter of gut at the height of an infection. Yet the intestinal mucosa of G. duodenalis-infected individuals is devoid of signs of overt inflammation. G. duodenalis infections can also occur concurrently with infections with other proinflammatory gastrointestinal pathogens. Little is known of whether and how this parasite can attenuate host inflammatory responses induced by other proinflammatory stimuli, such as a gastrointestinal pathogen. Identifying hitherto-unrecognized parasitic immunomodulatory pathways, the present studies demonstrated that G. duodenalis trophozoites attenuate secretion of the potent neutrophil chemoattractant interleukin-8 (CXCL8); these effects were observed in human small intestinal mucosal tissues and from intestinal epithelial monolayers, activated through administration of proinflammatory interleukin-1β or Salmonella enterica serovar Typhimurium. This attenuation is caused by the secretion of G. duodenalis cathepsin B cysteine proteases that degrade CXCL8 posttranscriptionally. Furthermore, the degradation of CXCL8 via G. duodenalis cathepsin B cysteine proteases attenuates CXCL8-induced chemotaxis of human neutrophils. Taken together, these data demonstrate for the first time that G. duodenalis trophozoite cathepsins are capable of attenuating a component of their host's proinflammatory response induced by a separate proinflammatory stimulus. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  8. Urinary Albumin and Interleukin-8 Levels are not Good Indicators of ...

    African Journals Online (AJOL)

    Introduction: Vesicoureteral reflux (VUR) is a risk factor for kidney scarring, hypertension and declining renal function. Standard diagnostic methods are invasive and can cause exposure to radiation and urinary tract infections (UTIs). We aimed to investigate urine albumin and interleukin-8 levels as markers of ongoing VUR ...

  9. Intraperitoneal interleukin-8 and neutrophil influx in the initial phase of a CAPD peritonitis

    NARCIS (Netherlands)

    Betjes, M. G.; Visser, C. E.; Zemel, D.; Tuk, C. W.; Struijk, D. G.; Krediet, R. T.; Arisz, L.; Beelen, R. H.

    1996-01-01

    OBJECTIVE: To investigate whether or not a change in dialysate interleukin-8 (IL-8) concentration precedes the onset of clinically overt peritonitis and is significant in the recruitment of granulocytes during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. DESIGN: CAPD

  10. Interleukin 8 and venous thrombosis: evidence for a role of inflammation in thrombosis

    NARCIS (Netherlands)

    van Aken, Benien E.; Reitsma, Pieter H.; Rosendaal, Frits R.

    2002-01-01

    Elevated plasma levels of interleukin 8 (IL-8) were previously shown to be associated with recurrent venous thrombosis. To assess the risk of venous thrombosis, IL-8 plasma concentrations were measured in patients and control subjects of the Leiden Thrombophilia Study (LETS). This population based

  11. Interleukin 8 in progression of hormone-dependent early breast cancer

    Indian Academy of Sciences (India)

    2017-04-18

    Apr 18, 2017 ... issue because some kind of adjuvant therapy is given to all breast cancer patients nowadays. Interleukin 8 (IL8) has been intensively examined in recent years as potential prognostic biomarker in different types of human cancers. IL8 is an inflammatory cytokine that belongs to the class of CXC chemokines, ...

  12. Interleukin-8 production by human mesothelial cells after direct stimulation with staphylococci

    NARCIS (Netherlands)

    Visser, C. E.; Steenbergen, J. J.; Betjes, M. G.; Meijer, S.; Arisz, L.; Hoefsmit, E. C.; Krediet, R. T.; Beelen, R. H.

    1995-01-01

    Mesothelial cells (MC) are able to produce interleukin-8 (IL-8) after stimulation with IL-1 beta or tumor necrosis factor alpha. The aim of our study was to investigate whether MC are able to produce IL-8 after direct stimulation with clinically relevant bacteria. We observed a significant IL-8

  13. Interleukin-8 induces motile behavior and loss of focal adhesions in primary fibroblasts

    DEFF Research Database (Denmark)

    Dunlevy, J R; Couchman, J R

    1995-01-01

    Interleukin-8 (IL-8) is a proinflammatory cytokine that promotes neutrophil migration. Although fibroblasts are known to secrete IL-8, the actions of this cytokine on fibroblasts have not been previously reported. We have found that in subconfluent populations of cultured primary fibroblasts, IL-8...

  14. Diagnostic performance of interleukin-6 and interleukin-8 for bacterial meningitis: a meta-analysis

    Science.gov (United States)

    Yao, Rong; Cao, Yu; Chen, Yao; Zeng, Zhi

    2015-01-01

    This study aimed to summarize the overall diagnostic performance of interleukin-6 and interleukin-8 in cerebrospinal fluid for bacterial meningitis through meta-analysis due to inconclusive results reported. Literature search was performed in PubMed and Embase to identify eligible studies. Data were retrieved and sensitivity, specificity, positive likelihood ratio/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR) were pooled. Summary receiver operating characteristic curve and the area under the curve (AUC) were calculated to evaluate their overall test performances. Thirteen studies were included for present meta-analysis. The summary estimates for interleukin-6 in diagnosing bacterial meningitis were: sensitivity, 0.91 (95% CI 0.81-0.96); specificity, 0.93 (95% CI 0.84-0.97); PLR, 12.38 (95% CI 5.42-28.29); NLR, 0.10 (95% CI 0.04-0.21); DOR, 129.76 (95% CI 41.48-405.88); and AUC 0.97 (95% CI 0.95-0.98). The corresponding summary performance estimates for interleukin-8 were as follows: sensitivity, 0.95 (95% CI 0.71-0.99); specificity, 0.89 (95% CI 0.77-0.95); PLR, 8.50 (95% CI, 3.83-18.86); NLR, 0.06 (95% CI 0.01-0.40); DOR, 154.25 (95% CI 14.56-1634.33); and AUC 0.95 (95% CI 0.93-0.97). Measurements of interleukin-6 and interleukin-8 play a valuable role in diagnosing bacterial meningitis. Nevertheless, their results should be interpreted in parallel with the results of routine tests and clinical symptoms. PMID:26221243

  15. Interleukin-8 induces motile behavior and loss of focal adhesions in primary fibroblasts

    DEFF Research Database (Denmark)

    Dunlevy, J R; Couchman, J R

    1995-01-01

    , this increase in cells lacking focal structures can be largely attributed to the production and subsequent autocrine action of a factor immunoprecipitated with an IL-8 antibody. Conversely, GRO-alpha, which has a high homology with IL-8, does not cause a similar increase in the percentage of cells lacking focal......Interleukin-8 (IL-8) is a proinflammatory cytokine that promotes neutrophil migration. Although fibroblasts are known to secrete IL-8, the actions of this cytokine on fibroblasts have not been previously reported. We have found that in subconfluent populations of cultured primary fibroblasts, IL-8...... causes an increase in the percentage of cells lacking focal adhesions. Most of the IL-8-stimulated cells not only exhibit a lack of focal adhesions but also have a migratory phenotype that includes a protrusive leading edge and trailing tail. In addition, IL-8 was found to promote primary fibroblast...

  16. The changes of interleukin-8 levels in gingival crevicular fluid in patients with periodontitis

    International Nuclear Information System (INIS)

    Zheng Jian; Li Hairu

    2011-01-01

    To explore the changes of interleukin-8 (IL-8) levels in gingival crevicular fluid (GCF) and their clinical significance in periodontitis patients. The IL-8 level in GCF from 67 teeth of 52 patients with adult periodontitis (AP), 37 teeth of 23 patients with rapidly progressive periodontitis (RPP) and 49 teeth of 31 normal controls were determined by RIA, and the clinical periodontoclasia indices of PD and AL were recorded. The results showed that the IL-8 levels in patients with AP and RPP were significantly higher than that of in health controls (P<0.01). The IL-8 was positively correlated to PD and AL. The results indicate that IL-8 may be one of the important cytokines in alveolar resorption of periodontoclasia. (authors)

  17. Prognostic value of interleukin-8 in AIDS-associated Pneumocystis carinii pneumonia

    DEFF Research Database (Denmark)

    Benfield, T L; Vestbo, Jørgen; Junge, Jette

    1995-01-01

    Interleukin-8 (IL-8) is a potent neutrophil chemoattractant and activator. Pneumocystis carinii pneumonia is associated with an accumulation of neutrophils in bronchoalveolar lavage (BAL) fluid. Thus, we hypothesized that IL-8 is involved in the pathogenesis of P. carinii pneumonia. BAL fluid...... and serum were prospectively collected in 76 consecutive HIV-infected patients with a primary episode of P. carinii pneumonia, as well as in 10 healthy control subjects. Patients were found to have elevated levels of IL-8 in BAL fluid compared with control subjects (p ... the course of P. carinii pneumonia. Comparing survivors with nonsurvivors, the median IL-8 level in BAL fluid was 127 (0 to 3,900) versus 584 (127 to 6,100) pg/ml (p

  18. Immunohistochemical expression of interleukin 8 in skin biopsies from patients with inflammatory acne vulgaris

    Directory of Open Access Journals (Sweden)

    El Maged Rabee A

    2007-01-01

    Full Text Available Abstract Background This study was conducted to evaluate the immunohistochemical (IHC expression of interleukin 8 (IL-8 in skin biopsies of inflammatory acne vulgaris (IAV in an attempt to understand the disease pathogenesis. Materials and methods A total of 58 biopsies, 29 from lesional IAV and 29 normal non lesional sites were immunostained for IL-8. The intensity of staining was evaluated in the epidermis and dermis and was scored as mild, moderate and severe. The expression was correlated with the clinical grade, disease course and histological changes. Results IL-8 immunoreactivity was expressed in lesional IAV compared to non lesional skin biopsies (p Conclusion We were able to demonstrate altered immunoreactivity of IL-8 in IAV compared to normal skin. Targeted therapy to block IL-8 production may hold promise in limiting the deleterious effects of IL-8-mediated inflammatory response and angiogenesis.

  19. Interleukin-8 and eicosanoid production in the lung during moderate to severe Pneumocystis carinii pneumonia in AIDS: a role of interleukin-8 in the pathogenesis of P. carinii pneumonia

    DEFF Research Database (Denmark)

    Benfield, T L; van Steenwijk, R; Nielsen, T L

    1995-01-01

    Pneumocystis carinii pneumonia (PCP) may cause severe respiratory distress. This is believed to be partly caused by the accumulation of neutrophils in the lung. Interleukin-8 (IL-8) and leukotriene B4 (LTB4) are potent neutrophil chemo-attractants and activators. Eicosanoids [i.e. prostaglandins...

  20. The dynamics of interleukin-8 and its interaction with human CXC receptor I peptide

    Energy Technology Data Exchange (ETDEWEB)

    Kendrick, Agnieszka; Holliday, Michael; Isern, Nancy G.; Zhang, Fengli; Camilloni, Carlo; Huynh, Chi; Vendruscolo, Michele; Armstrong, Geoffrey S.; Eisenmesser, Elan Z.

    2014-01-20

    Interleukin-8 (CXCL8, IL-8) is a pro-inflammatory chemokine important for the regulation of inflammatory and immune responses via its interaction with G-protein coupled receptors, including CXC receptor 1 (CXCR1). CXCL8 exists as both a monomer and as a dimer at physiological concentrations, yet the molecular basis of CXCL8 interaction with its receptor as well as the importance of CXCL8 dimer formation remain poorly characterized. Although several biological studies have indicated that both the CXCL8 monomer and dimer are active, biophysical studies have reported conflicting results regarding the binding of CXCL8 to CXCR1. To clarify this problem, we expressed and purified a peptide (hCXCR1pep) corresponding to the N-terminal region of human CXCR1 (hCXCR1) and utilized nuclear magnetic resonance (NMR) spectroscopy to interrogate the binding of wild-type CXCL8 and a previously reported mutant (CXCL8M) that stabilizes the monomeric form. Our data reveal that CXCL8M engages hCXCR1pep with a slightly higher affinity than CXCL8, and that CXCL8 does not dissociate upon binding hCXCR1pep. These investigations also indicate that CXCL8 exhibits inherent flexibility within its receptor-binding site on multiple timescales, which may help explain the versatility in this interleukin for engaging its target receptors.

  1. Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells

    International Nuclear Information System (INIS)

    Poghosyan, Anna; Patel, Jamie K.; Clifford, Rachel L.; Knox, Alan J.

    2016-01-01

    Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors of bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. -- Highlights: •A regulatory mechanism of CXCL8 transcriptional control in CF airways is proposed. •There was an increased binding of NF-κB and C/EBPβ transcription factors. •There was enhanced recruitment of BET proteins to the CXCL8 promoter. •Epigenetic modifications are responsible for the aberrant CXCL8 transcription.

  2. Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Poghosyan, Anna, E-mail: pannagos@yahoo.com; Patel, Jamie K.; Clifford, Rachel L.; Knox, Alan J., E-mail: alan.knox@nottingham.ac.uk

    2016-08-05

    Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors of bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. -- Highlights: •A regulatory mechanism of CXCL8 transcriptional control in CF airways is proposed. •There was an increased binding of NF-κB and C/EBPβ transcription factors. •There was enhanced recruitment of BET proteins to the CXCL8 promoter. •Epigenetic modifications are responsible for the aberrant CXCL8 transcription.

  3. A computational study of the chemokine receptor CXCR1 bound with interleukin-8

    Science.gov (United States)

    Wang, Yang; Severin Lupala, Cecylia; Wang, Ting; Li, Xuanxuan; Yun, Ji-Hye; Park, Jae-hyun; Jin, Zeyu; Lee, Weontae; Tan, Leihan; Liu, Haiguang

    2018-03-01

    CXCR1 is a G-protein coupled receptor, transducing signals from chemokines, in particular the interleukin-8 (IL8) molecules. This study combines homology modeling and molecular dynamics simulation methods to study the structure of CXCR1-IL8 complex. By using CXCR4-vMIP-II crystallography structure as the homologous template, CXCR1-IL8 complex structure was constructed, and then refined using all-atom molecular dynamics simulations. Through extensive simulations, CXCR1-IL8 binding poses were investigated in detail. Furthermore, the role of the N-terminal of CXCR1 receptor was studied by comparing four complex models differing in the N-terminal sequences. The results indicate that the receptor N-terminal affects the binding of IL8 significantly. With a shorter N-terminal domain, the binding of IL8 to CXCR1 becomes unstable. The homology modeling and simulations also reveal the key receptor-ligand residues involved in the electrostatic interactions known to be vital for complex formation. Project supported by the National Natural Science Foundation of China (Grant Nos. 11575021, U1530401, and U1430237) and the National Research Foundation of Korea (Grant Nos. NRF-2017R1A2B2008483 and NRF-2016R1A6A3A04010213).

  4. Effect of Periodontal Therapy on Crevicular Fluid Interleukin-6 and Interleukin-8 Levels in Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    Paschalina Goutoudi

    2012-01-01

    Full Text Available Purpose. The aim of this study was to analyse the levels of interleukin-6 (IL-6 and interleukin-8 (IL-8 in gingival crevicular fluid (GCF of patients with chronic periodontitis prior to and following surgical and/or nonsurgical periodontal therapy for a period of 32 weeks. Methods. GCF samples were obtained from 24 nondiseased and 72 diseased sites of 12 periodontal patients prior to as well as at 6, 16, and 32 weeks following non-surgical and surgical periodontal therapy. IL-6 and IL-8 levels were determined by enzyme-linked immunosorbent assay (ELISA. Results. Periodontal treatment improved all clinical parameters. Both treatment modalities resulted in similar IL-6 as well as IL-8 levels. Mean IL-6 and IL-8 concentrations were significantly higher in non-diseased compared to diseased sites and increased significantly following treatment in diseased sites. Mean total amounts of IL-6 and IL-8 (TAIL-6, TAIL-8 did not differ significantly between diseased and nondiseased sites, while following therapy TAIL-8 levels decreased significantly. Conclusions. The data suggest that periodontal therapy reduced the levels of IL-8 in GCF. However, a strong relationship between IL-6, IL-8 amounts in GCF and periodontal destruction and inflammation was not found.

  5. Inhibition of endothelial interleukin-8 production and neutrophil transmigration by Staphylococcus aureus beta-hemolysin.

    Science.gov (United States)

    Tajima, Akiko; Iwase, Tadayuki; Shinji, Hitomi; Seki, Keiko; Mizunoe, Yoshimitsu

    2009-01-01

    Neutrophils play a crucial role in the host response to infection with Staphylococcus aureus, which is a major human pathogen capable of causing life-threatening disease. Interleukin-8 (IL-8) is a potent chemoattractant and activator of neutrophils. We previously reported that S. aureus secretes a factor that suppresses IL-8 production by human endothelial cells. Here we isolated an inhibitor of IL-8 production from the supernatant and identified it as staphylococcal beta-hemolysin. Beta-hemolysin reduced IL-8 production without cytotoxicity to endothelial cells. Pretreatment with beta-hemolysin decreased the expression of both IL-8 mRNA and protein induced by tumor necrosis factor alpha (TNF-alpha). Migration of neutrophils across TNF-alpha-activated endothelium was also inhibited by beta-hemolysin. In contrast, beta-hemolysin had no effect on intercellular adhesive molecule 1 expression in activated endothelial cells. These results showed that beta-hemolysin produced by S. aureus interferes with inflammatory signaling in endothelial cells and may help S. aureus evade the host immune response.

  6. Expression of antimicrobial peptides and interleukin-8 during early stages of inflammation: An experimental gingivitis study.

    Science.gov (United States)

    Dommisch, H; Staufenbiel, I; Schulze, K; Stiesch, M; Winkel, A; Fimmers, R; Dommisch, J; Jepsen, S; Miosge, N; Adam, K; Eberhard, J

    2015-12-01

    In the oral cavity, the epithelial surface is constantly exposed to a number of different microorganisms that are organized in a well-structured biofilm. The aim of this study was to monitor gingival expression of antimicrobial peptides (AMPs) and interleukin-8 (IL-8) in an early gingivitis model. Experimental gingivitis was allowed to develop in healthy volunteers (n = 17). Bleeding on probing (BOP%) and gingival crevicular fluid volume (GCF) were assessed at baseline and day 1, 3, 5, 7 and 14. Expression of AMPs (human beta-defensin-2, hBD-2; CC-chemokine ligand 20, CCL20; psoriasin, pso/S100A7) and IL-8 was analyzed by immunohistochemistry in gingival biopsies. In addition, hBD-2 and IL-8 protein expression was monitored in GCF using the ELISA technology. Experimental gingivitis gradually developed with an increase in BOP scores and GCF volume over time. In GCF, elevated concentrations of hBD-2 and IL-8 were monitored at day 1, 5 and 7 (p ≤ 0.0002). Immunohistochemical analysis of gingival sections demonstrated increased staining for hBD-2 at day 3, whereas the CCL20, pso/S100A7, and IL-8 expression was increased at later time points (p gingival inflammation. Differential temporal expression for AMPs may ensure a constant antimicrobial activity against changes in the bacterial composition of the growing dental biofilm. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Association of Enterovirus 71 encephalitis with the interleukin-8 gene region in Chinese children.

    Science.gov (United States)

    Li, Jian; Lin, Aiwei; Yu, Chengwen; Zhang, Zhaofang; Xu, Daoyan; Hu, Wei; Liu, Liyan; Wang, Shaoning; Nie, Xiuzhen; Sun, Wenhui; Gai, Zhongtao; Chen, Zongbo

    2015-06-01

    The study was performed in 36 Chinese patients with Enterovirus 71 (EV71) encephalitis and 141 patients with EV71-related hand, foot and mouth disease (HFMD) without encephalitis. Genotyping was determined by polymerase chain reaction- restriction fragment length polymorphism. Patients with EV71 encephalitis had a significantly higher frequency of interleukin-8 (IL-8)-251TT genotype than patients with EV71-related HFMD without encephalitis (55.6% vs 31.2%, p = 0.023). The frequency of IL-8-251T alleles was significantly higher among patients with EV71 encephalitis than in patients with EV71-related HFMD without encephalitis (72.2% vs 58.9%, odds ratio 1.8, 95% confidence interval 1.0-3.2, p = 0.038). There were significant differences in gender, age, fever days, white blood cell count, C-reactive protein and blood glucose concentration and IL-8 levels among genotypes of IL-8-251A/T in EV71-infected patients, but no significant differences in alanine or aspartate aminotransferase, creatine kinase-myocardial isozyme and cerebrospinal fluid in patients with EV71 encephalitis. These findings suggest that the IL-8-251T allele is associated with susceptibility to EV71 encephalitis in Chinese patients.

  8. Characterization of buffalo interleukin 8 (IL-8 and its expression in endometritis

    Directory of Open Access Journals (Sweden)

    Ahlam A. Abou Mossallam

    2015-06-01

    Full Text Available River buffalo (Bubalus bubalis bubalis with a population over 135 million heads is an important livestock. Interleukin 8 (IL-8 is a member of the chemokine family and is an important chemoattractant for neutrophils associated with a wide variety of inflammatory diseases such as endometritis. Tissue samples from the mammary gland, uterus and ovary were obtained from river buffalo (Mediterranean type with and without endometritis. Bacteriological examination showed the presence of both gram positive and negative in all buffalo with endometritis. RNA extraction and complementary DNA (cDNA synthesis were conducted from all tissues. Specific primer for IL8 full coding regions was designed using known cDNA sequences of Bubalus bubalis, Genbank accession number AY952930.1. IL-8 gene expression was investigated in buffalo tissues. Expression of IL-8 in buffalo with endometritis was found to increase significantly over buffalo without endometritis only in the uterus (P = 0.0159. PCR products from uterus tissues (target organs of buffalo with and without endometritis, were purified and sequenced. No polymorphic sites were detected in the investigated samples. IL-8 cDNA nucleotide sequences of buffalo with and without endometritis were 100% identical (accession number JX413057. Buffalo IL8 cDNAs were compared with corresponding sequences of member of subfamily Bovinae (buffalo and cattle and subfamily Caprinae (sheep and goat. IL-8 species specific differences were identified.

  9. Interleukin-8 for diagnosis of neonatal sepsis: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Min Zhou

    Full Text Available Neonatal sepsis (NS is a life-threatening disorder and an important cause of morbidity and mortality in neonates. Previous studies showed that interleukin 8 (IL-8 may effectively and rapidly diagnose NS.We conducted the systematic review and meta-analysis to investigate the diagnostic value of the IL-8 in NS.The literature was searched in PUBMED, EMBASE, Cochrane Library, CNKI, VIP and other Chinese Medical Databases during October 1998 to January 2014 using set search criteria. Each included study was evaluated by quality assessment of diagnostic accuracy studies tool. Two investigators independently extracted the data and study characteristics, and disagreements, if any, were resolved by consensus. Meta-disc software was used to calculate the pooled sensitivity, specificity and summary diagnostic odds ratio (SDOR, I² or Cochrane Q to test heterogeneity, and meta-regression to investigate the source of heterogeneity. Funnel plots were used to test the potential presence of publication bias. False-positive report probability (FPRP was calculated to confirm the significance of the results.Eight studies (548 neonates were included in this meta-analysis. The pooled sensitivity and specificity of IL-8 were 0.78 and 0.84, respectively, which had moderate accuracy in the diagnosis of NS. The pooled diagnostic odds ratio (DOR and area under curve (AUC was 21.64 and 0.8908 (Q*=0.8215, respectively. The diagnostic threshold analysis showed that there was no threshold effect. The meta-regression analysis showed the cut-off, QUADAS and onset time have no effect on the heterogeneity. The funnel plots showed the existence of publication bias.Meta-analysis showed IL-8 had a moderate accuracy (AUC=0.8908 for the diagnosis of NS. IL-8 is a helpful biomarker for early diagnosis of NS. However, we should combine the results with clinical symptoms and signs, laboratory and microbial results.

  10. Structural analysis of the interleukin-8/glycosaminoglycan interactions by amide hydrogen/deuterium exchange mass spectrometry.

    Science.gov (United States)

    Hofmann, Tommy; Samsonov, Sergey A; Pichert, Annelie; Lemmnitzer, Katharina; Schiller, Jürgen; Huster, Daniel; Pisabarro, M Teresa; von Bergen, Martin; Kalkhof, Stefan

    2015-11-01

    The recruitment of different chemokines and growth factors by glycosaminoglycans (GAGs) such as chondroitin sulfate or hyaluronan plays a critical role in wound healing processes. Thus, there is a special interest in the design of artificial extracellular matrices with improved properties concerning GAG interaction with common regulating proteins. In this study, amide hydrogen/deuterium (H/D) exchange mass spectrometry (HDX MS) combined with molecular modeling and docking experiments was used to obtain structural models of proinflammatory chemokine interleukin-8 (IL-8) in complex with hexameric chondroitin sulfate. Experiments on the intact protein showed a difference in deuterium labeling of IL-8 due to chondroitin sulfate binding. The extent of deuteration was reduced from 24% to 13% after 2 min exchange time, which corresponds to a reduced exchange of approximately 10 backbone amides. By local HDX MS experiments, H/D exchange information on the complete sequence of IL-8 could be obtained. A significantly reduced H/D exchange, especially of the C-terminal α-helical region comprising amino acids 70-77 and to the loop comprising amino acids 27-29 was observed in the presence of chondroitin sulfate. HDX MS data were used to model the IL-8/chondroitin sulfate complex. The binding interface of IL-8 and chondroitin sulfate determined this way correlated excellently with the corresponding NMR based atomistic model previously published. Our results demonstrate that HDX-MS in combination with molecular modeling is a valuable approach for the analysis of protein/GAG complexes at physiological pH, temperature, and salt concentration. The fact that HDX-MS requires only micrograms of protein and GAGs makes it a very promising technique to address protein-GAG interactions. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Doxycycline decreases production of interleukin-8 in a549 human lung epithelial cells

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    Hoyt JC

    2013-03-01

    Full Text Available Doxycycline is an antibiotic that possess anti-inflammatory properties. These anti-inflammatory properties make doxycycline an attractive candidate for possible treatments for a variety of common chronic obstructive airway diseases. Interleukin-8 (IL-8 is a major inflammatory chemokine and a powerful chemo-attractant for both neutrophils and monocytes. We hypothesized that doxycycline might exert its anti-inflammatory effects, at least in part, by modulating IL-8 production. To test this hypothesis, A549 human lung epithelial cells were stimulated with cytomix (IL-1beta, TNF-alpha and gamma-IFN in the presence or absence of varying concentrations of doxycycline. Doxycycline decreased IL-8 protein production in a concentration- and time-dependent manner. In the presence of 30 microg/ml doxycycline IL-8 protein production was decreased by 63% through out a 30 hr time course. In chemotaxis assays monocyte and neutrophil migration was decreased by 55% and 57% respectively. Reverse transcriptase-polymerase chain reaction (RT-PCR experiments suggest that doxycycline does not decrease expression of IL-8 mRNA and that use of the RNA polymerase II inhibitor DRB indicates that doxycycline does not effect stability of this mRNA. In the presence of doxycycline p38-alpha mitogen-activated protein kinase (MAPK expression is decreased by 36% in cytomix-stimulated cells. These data demonstrate that doxycycline can modulate IL-8 release and suggest that it has potential as an anti-inflammatory in those disorders where IL-8 is an important inflammatory mediator.

  12. Plasma Interleukin-8 and Endothelin-1 in Symptomatic and Asymptomatic Children

    International Nuclear Information System (INIS)

    Radwan, Z.; El-Abiad, N.; Soliman, M. S.; Ali, A.I.; Ali, G.S.

    2004-01-01

    This study was designed to evaluate the extent to which IL-8 and endothelin-1 are involved in the development of acute exacerbation of atopic asthma. Two asthmatic groups, each of 20 patients were studied, the asymptomatic group where patients were free of symptoms and the symptomatic group where patients were suffering from acute exacerbation of their asthma. Both of asthmatic groups were subclassified into mild and moderate subgroups, each of 10 patients according to the asthma severity. All subjects were subjected to chest X-ray and peak expiratory flow rate (PEFR) recording for sub-classification of patients, skin prick testing using common allergens (patients only) for the identification of atopic asthmatic patients and laboratory investigations including complete blood count (CBC), absolute eosi-nophil count (AEC), urine and stool exam-ination, total serum 1 gE level, plasma inter-leukin-8 (IL-8) level and plasma endothelin-1 (ET-1) level. The data obtained revealed non-significant differences between the studied groups as regards AEC, while serum total 1 gE of the asthmatic groups showed highly significant elevations in comparison to control group. Also, There were highly significant elevations in plasma endothelin-1 and plasma IL-8 levels of the symptomatic asthmatic subgroups in comparison to control group and asymptomatic asthmatic subgroups in comparison to control group and asymptomatic asthmatic subgroups. In conclusion: although it is clear now that IL-8 and ET-1 are involved in acute exacerbation of atopic asthmatic patients, a causal link between those mediators and development of the exacerbation has not been definitively established. Surely, those mediators, their receptors, synthesis and degradation pathways offer potentially important therapeutic targets

  13. Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment.

    Science.gov (United States)

    Kim, Jong-Hyuk; Frantz, Aric M; Anderson, Katie L; Graef, Ashley J; Scott, Milcah C; Robinson, Sally; Sharkey, Leslie C; O'Brien, Timothy D; Dickerson, Erin B; Modiano, Jaime F

    2014-04-15

    Interleukin-8 (IL-8) gene expression is highly up-regulated in canine hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is unknown. We investigated the expression of IL-8 in canine HSA tissues and cell lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL-8 protein, and IL-8 receptor were variable among different tumor samples and cell lines, but they showed stable steady states in each cell line. Upon the addition of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that their IL-8 receptors are functional and that IL-8 binding activates relevant signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of endogenous IL-8 by neutralizing anti-IL-8 antibody (α-IL-8 Ab) affected HSA cell proliferation or survival in vitro. To assess potential effects of IL-8 in other tumor constituents, we stratified HSA cell lines and whole tumor samples into "IL-8 high" and "IL-8 low" groups. Genome-wide gene expression profiling showed that samples in the "IL-8 high" tumor group were enriched for genes associated with a "reactive microenvironment," including activation of coagulation, inflammation, and fibrosis networks. Based on these findings, we hypothesized that the effects of IL-8 on these tumors were mostly indirect, regulating interactions with the microenvironment. This hypothesis was supported by in vivo xenograft experiments where survival and engraftment of tumor cells was inhibited by administration of neutralizing α-IL-8 Ab. Together, our results suggest that IL-8 contributes to establishing a permissive microenvironment during the early stages of tumorigenesis in HSA. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. The effects of interleukin-8 on airway smooth muscle contraction in cystic fibrosis

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    Safka Katherine

    2008-12-01

    Full Text Available Abstract Background Many cystic fibrosis (CF patients display airway hyperresponsiveness and have symptoms of asthma such as cough, wheezing and reversible airway obstruction. Chronic airway bacterial colonization, associated with neutrophilic inflammation and high levels of interleukin-8 (IL-8 is also a common occurrence in these patients. The aim of this work was to determine the responsiveness of airway smooth muscle to IL-8 in CF patients compared to non-CF individuals. Methods Experiments were conducted on cultured ASM cells harvested from subjects with and without CF (control subjects. Cells from the 2nd to 5th passage were studied. Expression of the IL-8 receptors CXCR1 and CXCR2 was assessed by flow cytometry. The cell response to IL-8 was determined by measuring intracellular calcium concentration ([Ca2+]i, cell contraction, migration and proliferation. Results The IL-8 receptors CXCR1 and CXCR2 were expressed in both non-CF and CF ASM cells to a comparable extent. IL-8 (100 nM induced a peak Ca2+ release that was higher in control than in CF cells: 228 ± 7 versus 198 ± 10 nM (p 20 in CF than in control cells. In addition, MLC20 expression was also increased in CF cells. Exposure to IL-8 induced migration and proliferation of both groups of ASM cells but was not different between CF and non-CF cells. Conclusion ASM cells of CF patients are more contractile to IL-8 than non-CF ASM cells. This enhanced contractility may be due to an increase in the amount of contractile protein MLC20. Higher expression of MLC20 by CF cells could contribute to airway hyperresponsiveness to IL-8 in CF patients.

  15. Cell-associated interleukin-8 in cord blood of term and preterm infants.

    Science.gov (United States)

    Dembinski, J; Behrendt, D; Heep, A; Dorn, C; Reinsberg, J; Bartmann, P

    2002-03-01

    To assess the effect of gestational age and labor on the interleukin-8 (IL-8) concentration in whole cord blood and serum, IL-8 levels were determined simultaneously in cord blood serum and lysate in 134 infants. Following the elimination of some of the samples due to exclusion criteria, the data for 99 uninfected infants (71 term and 28 preterm) and 9 infants with neonatal bacterial infection delivered either vaginally or by elective or emergency cesarean section were analyzed. The effects of labor and gestational age were tested by analysis of variance. IL-8 was not detectable in the serum of 25 infants, whereas IL-8 levels in whole blood were measurable in all of the samples. The median IL-8 conncentrations in whole cord blood lysate were 106 pg/ml (range, 20 to 415 pg/ml) in preterm infants and 176 pg/ml (range, 34 to 1,667 pg/ml) in term infants. In contrast to the IL-8 levels in serum, IL-8 levels in whole blood were reduced after ECS. Gestational age had no independent effect on the IL-8 concentrations in either serum or whole blood; these concentrations increased in infected infants after labor. We conclude that the neonatal proinflammatory response to labor stress was more evident in the concentrations of IL-8 in whole blood than in serum. The levels of IL-8 in whole-blood lysate reflect proinflammatory stimulation in neonates and may be a useful diagnostic tool for the early diagnosis of neonatal infection.

  16. Molecular characterization of Legionella pneumophila-induced interleukin-8 expression in T cells

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    Mukaida Naofumi

    2010-01-01

    Full Text Available Abstract Background Legionella pneumophila is the causative agent of human Legionnaire's disease. During infection, the bacterium invades macrophages and lung epithelial cells, and replicates intracellularly. However, little is known about its interaction with T cells. We investigated the ability of L. pneumophila to infect and stimulate the production of interleukin-8 (IL-8 in T cells. The objective of this study was to assess whether L. pneumophila interferes with the immune system by interacting and infecting T cells. Results Wild-type L. pneumophila and flagellin-deficient Legionella, but not L. pneumophila lacking a functional type IV secretion system Dot/Icm, replicated in T cells. On the other hand, wild-type L. pneumophila and Dot/Icm-deficient Legionella, but not flagellin-deficient Legionella or heat-killed Legionella induced IL-8 expression. L. pneumophila activated an IL-8 promoter through the NF-κB and AP-1 binding regions. Wild-type L. pneumophila but not flagellin-deficient Legionella activated NF-κB, p38 mitogen-activated protein kinase (MAPK, Jun N-terminal kinase (JNK, and transforming growth factor β-associated kinase 1 (TAK1. Transfection of dominant negative mutants of IκBα, IκB kinase, NF-κB-inducing kinase, TAK1, MyD88, and p38 MAPK inhibited L. pneumophila-induced IL-8 activation. Inhibitors of NF-κB, p38 MAPK, and JNK blocked L. pneumophila-induced IL-8 expression. In addition, c-Jun, JunD, cyclic AMP response element binding protein, and activating transcription factor 1, which are substrates of p38 MAPK and JNK, bound to the AP-1 site of the IL-8 promoter. Conclusions Taken together, L. pneumophila induced a flagellin-dependent activation of TAK1, p38 MAPK, and JNK, as well as NF-κB and AP-1, which resulted in IL-8 production in human T cells, presumably contributing to the immune response in Legionnaire's disease.

  17. Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong-Hyuk, E-mail: jhkim@umn.edu [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Frantz, Aric M.; Anderson, Katie L.; Graef, Ashley J.; Scott, Milcah C. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Robinson, Sally [Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Sharkey, Leslie C. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); O' Brien, Timothy D. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Dickerson, Erin B. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Modiano, Jaime F., E-mail: modiano@umn.edu [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States)

    2014-04-15

    Interleukin-8 (IL-8) gene expression is highly up-regulated in canine hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is unknown. We investigated the expression of IL-8 in canine HSA tissues and cell lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL-8 protein, and IL-8 receptor were variable among different tumor samples and cell lines, but they showed stable steady states in each cell line. Upon the addition of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that their IL-8 receptors are functional and that IL-8 binding activates relevant signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of endogenous IL-8 by neutralizing anti-IL-8 antibody (α-IL-8 Ab) affected HSA cell proliferation or survival in vitro. To assess potential effects of IL-8 in other tumor constituents, we stratified HSA cell lines and whole tumor samples into “IL-8 high” and “IL-8 low” groups. Genome-wide gene expression profiling showed that samples in the “IL-8 high” tumor group were enriched for genes associated with a “reactive microenvironment,” including activation of coagulation, inflammation, and fibrosis networks. Based on these findings, we hypothesized that the effects of IL-8 on these tumors were mostly indirect, regulating interactions with the microenvironment. This hypothesis was supported by in vivo xenograft experiments where survival and engraftment of tumor cells was inhibited by administration of neutralizing α-IL-8 Ab. Together, our results suggest that IL-8 contributes to establishing a permissive microenvironment during the early stages of tumorigenesis in HSA. - Highlights: • IL-8 is expressed in canine hemangiosarcoma tumor samples and cell lines. • IL-8 transduces a relevant biological signal in canine hemangiosarcoma cells. • IL-8 gene signature is associated

  18. Interleukin-8 as a prognostic serum marker in canine mammary gland neoplasias.

    Science.gov (United States)

    Gelaleti, Gabriela Bottaro; Jardim, Bruna Victorasso; Leonel, Camila; Moschetta, Marina Gobbe; Zuccari, Debora Ap Pires de Campos

    2012-04-15

    Mammary gland tumors in female dogs are an excellent model for the clinic-pathological, diagnostic and prognostic investigation of mammary neoplasias. Prognostic and predictive markers are effective in research and routine diagnosis. Interleukins play a fundamental role in cancer, with a particular function in tumor growth, invasion and metastatic potential. Interleukin-8 (IL-8) is known to possess tumorigenic and pro-angiogenic properties, and its overexpression is seen in a number of human tumors. IL-8 serum levels were determined and correlated with the clinic-pathological features and clinical evolution of mammary gland neoplasias in female dogs. IL-8 was measured by an immunoenzymatic assay in 30 female dogs with mammary neoplasias within a 12 month follow-up and in 50 control animals. The correlation between IL-8 concentration and clinical parameters was investigated. A statistically significant difference in the IL-8 serum levels was found in tumor-bearing dogs compared to the controls. In addition, when the individual parameters were evaluated, IL-8 content showed a positive correlation with the tumor progression, lymph node involvement, recurrence and death. Single and multivariate analyses showed associations between tumor recurrence, metastasis, high clinical staging and high IL-8, and also with the death risk. This was also consistent with the high IL-8 content in dogs showing tumor recurrence and metastasis. IL-8 superexpression has been detected in a number of human tumors, usually associated with a poor prognostic. Besides promoting angiogenesis, IL-8 is strongly related with the metastatic phenotype of mammary tumor cells. High IL-8 concentration was found in mammary gland cancer patients with advanced disease stages. Our results show that IL-8 can be used as a non-invasive prognostic marker for mammary gland cancer, and can be useful for the prediction of disease progression and recurrence in dogs with mammary neoplasias. The increased level of

  19. Label-free electrochemical impedance biosensor to detect human interleukin-8 in serum with sub-pg/ml sensitivity

    OpenAIRE

    Sharma, R.; Deacon, S.E.; Nowak, D.; George, S.E.; Szymonik, M.P.; Tang, A.A.S.; Tomlinson, D.C.; Davies, A.G.; McPherson, M.J.; W?lti, C.

    2016-01-01

    Biosensors with high sensitivity and short time-to-result that are capable of detecting biomarkers in body fluids such as serum are an important prerequisite for early diagnostics in modern healthcare provision. Here, we report the development of an electrochemical impedance-based sensor for the detection in serum of human interleukin-8 (IL-8), a pro-angiogenic chemokine implicated in a wide range of inflammatory diseases. The sensor employs a small and robust synthetic non-antibody capture p...

  20. Met receptor tyrosine kinase signaling induces secretion of the angiogenic chemokine interleukin-8/CXCL8 in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Kristen S Hill

    Full Text Available At diagnosis, the majority of pancreatic cancer patients present with advanced disease when curative resection is no longer feasible and current therapeutic treatments are largely ineffective. An improved understanding of molecular targets for effective intervention of pancreatic cancer is thus urgent. The Met receptor tyrosine kinase is one candidate implicated in pancreatic cancer. Notably, Met is over expressed in up to 80% of invasive pancreatic cancers but not in normal ductal cells correlating with poor overall patient survival and increased recurrence rates following surgical resection. However the functional role of Met signaling in pancreatic cancer remains poorly understood. Here we used RNA interference to directly examine the pathobiological importance of increased Met signaling for pancreatic cancer. We show that Met knockdown in pancreatic tumor cells results in decreased cell survival, cell invasion, and migration on collagen I in vitro. Using an orthotopic model for pancreatic cancer, we provide in vivo evidence that Met knockdown reduced tumor burden correlating with decreased cell survival and tumor angiogenesis, with minimal effect on cell growth. Notably, we report that Met signaling regulates the secretion of the pro-angiogenic chemokine interleukin-8/CXCL8. Our data showing that the interleukin-8 receptors CXCR1 and CXCR2 are not expressed on pancreatic tumor cells, suggests a paracrine mechanism by which Met signaling regulates interleukin-8 secretion to remodel the tumor microenvironment, a novel finding that could have important clinical implications for improving the effectiveness of treatments for pancreatic cancer.

  1. Interleukin-8 and eicosanoid production in the lung during moderate to severe Pneumocystis carinii pneumonia in AIDS: a role of interleukin-8 in the pathogenesis of P. carinii pneumonia

    DEFF Research Database (Denmark)

    Benfield, T L; van Steenwijk, R; Nielsen, T L

    1995-01-01

    Pneumocystis carinii pneumonia (PCP) may cause severe respiratory distress. This is believed to be partly caused by the accumulation of neutrophils in the lung. Interleukin-8 (IL-8) and leukotriene B4 (LTB4) are potent neutrophil chemo-attractants and activators. Eicosanoids [i.e. prostaglandins...... in the corticosteroid-treated patients from days 0-10, whereas no change was detected in the placebo group. No change in levels of LTB4, LTC4, PGE2, PGF2a and PLA2 were detected cover time in either treatment group. This study establishes a correlation between IL-8, BAL neutrophilia and P(A-a)O2, and suggests a role...

  2. Crevicular fluid levels of interleukin-8, interleukin-17 and soluble intercellular adhesion molecule-1 after regenerative periodontal therapy.

    Science.gov (United States)

    Erdemir, Ebru Olgun; Hendek, Meltem Karsiyaka; Keceli, H Gencay; Apan, Teoman Z

    2015-01-01

    The aim of this study is to evaluate the influence of regenerative periodontal therapy on clinical parameters and interleukin-8 (IL-8), IL-17 and soluble intercellular adhesion molecule-1 (sICAM-1) levels in gingival crevicular fluid (GCF) of subjects with chronic periodontitis (CP). Fifteen patients received demineralized freeze-dried bone allograft (DFDBA) surgically to the site of infrabony defect. Clinical periodontal indices were recorded, and GCF samples were collected at baseline and at the 6(th) and the 9(th) month after the surgery. Except plaque index, all clinical parameters improved following surgery (P periodontal healing after demineralized freeze-dried bone grafting.

  3. Interleukin-8 and leukotriene B4 in bronchoalveolar lavage fluid from HIV-infected patients with bacterial pneumonia

    DEFF Research Database (Denmark)

    Krarup, E; Vestbo, Jørgen; Benfield, T L

    1997-01-01

    Human immunodeficiency virus (HIV)-infected patients are at increased risk of contracting bacterial infections, mainly pneumonia. Despite this, little is known about immunopathogenic mechanisms in HIV-related bacterial pneumonia. This paper investigates the presence of the neutrophil chemotactic...... mediators, interleukin-8 (IL_8) and leukotriene B4 (LTB4), in bronchoalveolar lavage (BAL) fluid from 27 HIV-infected patients with bacterial pneumonia. Significantly elevated levels of IL-8 were found in BAL fluid of patients with bacterial pneumonia [529 pg ml-1 (296-1161 pg ml-1)] compared to matched...... patients with Pneumocystis carinii pneumonia (PCP) [59 pg ml-1 (42-254 pg ml-1)] and healthy controls [58 pg ml-1 (37-82 pg ml-1)]. Levels of LTB4 were not elevated during bacterial pneumonia when compared to PCP patients and healthy controls. Furthermore, a positive correlation was found between IL-8...

  4. Decreased Pulmonary Function in School Children in Western Japan after Exposures to Asian Desert Dusts and Its Association with Interleukin-8

    OpenAIRE

    Masanari Watanabe; Hisashi Noma; Jun Kurai; Hiroyuki Sano; Rumiko Saito; Satoshi Abe; Yutaka Kimura; Setsuya Aiba; Mitsuo Oshimura; Akira Yamasaki; Eiji Shimizu

    2015-01-01

    The objective of the study was to investigate the influence of Asian dust storms (ADS) on pulmonary function of school children and the relationship of this effect with interleukin-8. Morning peak expiratory flow (PEF) was measured daily in 399 children from April to May 2012 and in 384 of these children from March to May 2013. The data were analyzed for an association between ADS events and PEF by linear mixed models. Interleukin-8 transcriptional activity was assessed in THP-G8 cells stimul...

  5. Single Intramammary Infusion of Recombinant Bovine Interleukin-8 at Dry-Off Induces the Prolonged Secretion of Leukocyte Elastase, Inflammatory Lactoferrin-Derived Peptides, and Interleukin-8 in Dairy Cows

    Directory of Open Access Journals (Sweden)

    Atsushi Watanabe

    2012-01-01

    Full Text Available A single intramammary infusion of recombinant bovine interleukin-8 (IL-8 at 50 μg/quarter/head, but not 10 μg/quarter/head, induced clinical mastitis in three of four cows during the dry-off period, resulting in an elevated rectal temperature, redness and swelling of the mammary gland, extensive polymorphonuclear leukocyte (PMNL infiltration, and milk clot formation from 1 to 28 days post infusion (PI. In the mammary secretions of the mastitic glands, high levels of IL-8 were sustained from 8 hours to 28 days PI, peaking at 1–3 days PI. The levels of leukocyte-derived elastase and inflammatory 22 and 23 kDa lactoferrin derived peptides (LDP were also increased in the mammary secretions from the mastitic glands. In addition to the experimentally induced mastitis, the mammary secretions from the glands of cattle with spontaneous Staphylococcus aureus dry-period mastitis displayed milk clot formations and significant increases in their levels of PMNL counts, elastase, LDP, and IL-8, compared with those of the mammary secretions from the uninfected glands. These results suggest that after an intramammary infusion of IL-8 has elicited inflammatory responses, it induces the prolonged secretion of elastase, inflammatory LDP, and IL-8, and that long-lasting IL-8-induced inflammatory reactions are involved in the pathogenesis of S. aureus dry-period mastitis.

  6. Histamine H4 Receptor mediates interleukin-8 and TNF-α release in human mast cells via multiple signaling pathways.

    Science.gov (United States)

    Chen, X-F; Zhang, Z; Dou, X; Li, J-J; Zhang, W; Yu, Y-Y; Yu, B; Yu, B

    2016-01-27

    Histamine, mainly produced by mast cells, is an important inflammatory mediator in immune response. Recently Histamine H4 Receptor (H4R) was also identified in mast cells, from which pro-inflammatory cytokines and chemokines are released. However, the mechanism of how H4R mediates these cytokines and chemokines release in mast cells was still unclear. To further explore the role of H4R in the immune inflammatory response in mast cells, we tested the release of inflammatory cytokine tumor necrosis factor-α (TNF-α), chemokine interleukin-8 (IL-8) and the relevant signaling pathways activated by H4R on LAD2 cells (a human mast cell line). We found that the release of IL-8 and TNF-α were blocked by inhibitors of PI3K, ERK and Ca2+-Calcineurin-NFAT signaling pathways, while the release of these cytokines and chemokines were enhanced by the inhibitor of P38 signaling pathway. However, inhibitors of the JNK and NF-κB signaling pathways had little effect on the expression of the pro-inflammatory mediators. Moreover, activation of the H4R could induce phosphorylation of ERK, p38 and AKT in mast cells. In conclusion, we found that H4R mediates the release of inflammatory cytokine TNF-α and chemokine IL-8 in human mast cells via PI3K, Ca2+-Calcineurin-NFAT and MAPKs signaling pathways.

  7. In vivo imaging of transiently transgenized mice with a bovine interleukin 8 (CXCL8 promoter/luciferase reporter construct.

    Directory of Open Access Journals (Sweden)

    Fabio Franco Stellari

    Full Text Available One of the most remarkable properties of interleukin 8 (CXCL8/IL-8, a chemokine with known additional functions also in angiogenesis and tissue remodeling, is the variation of its expression levels. In healthy tissues, IL-8 is barely detectable, but it is rapidly induced by several folds in response to proinflammatory cytokines, bacterial or viral products, and cellular stress. Although mouse cells do not bear a clear homologous IL-8 gene, the murine transcriptional apparatus may well be capable of activating or repressing a heterologous IL-8 gene promoter driving a reporter gene. In order to induce a transient transgenic expression, mice were systemically injected with a bovine IL-8 promoter-luciferase construct. Subsequently mice were monitored for luciferase expression in the lung by in vivo bioluminescent image analysis over an extended period of time (up to 60 days. We demonstrate that the bovine IL-8 promoter-luciferase construct is transiently and robustly activated 3-5 hours after LPS and TNF-α instillation into the lung, peaking at 35 days after construct delivery. Bovine IL-8 promoter-luciferase activation correlates with white blood cell and neutrophil infiltration into the lung. This study demonstrates that a small experimental rodent model can be utilized for non-invasively monitoring, through a reporter gene system, the activation of an IL-8 promoter region derived from a larger size animal (bovine. This proof of principle study has the potential to be utilized also for studying primate IL-8 promoter regions.

  8. Induction of interleukin-8 by Naegleria fowleri lysates requires activation of extracellular signal-regulated kinase in human astroglial cells.

    Science.gov (United States)

    Kim, Jong-Hyun; Sohn, Hae-Jin; Lee, Sang-Hee; Kwon, Daeho; Shin, Ho-Joon

    2012-08-01

    Naegleria fowleri is a pathogenic free-living amoeba which causes primary amoebic meningoencephalitis in humans and experimental animals. To investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astroglial cells was investigated following treatment with N. fowleri lysates. We demonstrated that N. fowleri are potent inducers for the expression of interleukin-8 (IL-8) genes in human astroglial cells which was preceded by activation of extracellular signal-regulated kinase (ERK). In addition, N. fowleri lysates induces the DNA binding activity of activator protein-1 (AP-1), an important transcription factor for IL-8 induction. The specific mitogen-activated protein kinase kinase/ERK inhibitor, U0126, blocks N. fowleri-mediated AP-1 activation and subsequent IL-8 induction. N. fowleri-induced IL-8 expression requires activation of ERK in human astroglial cells. These findings indicate that treatment of N. fowleri on human astroglial cells leads to the activation of AP-1 and subsequent expression of IL-8 which are dependent on ERK activation. These results may help understand the N. fowleri-mediated upregulation of chemokine and cytokine expression in the astroglial cells.

  9. Label-free electrochemical impedance biosensor to detect human interleukin-8 in serum with sub-pg/ml sensitivity.

    Science.gov (United States)

    Sharma, R; Deacon, S E; Nowak, D; George, S E; Szymonik, M P; Tang, A A S; Tomlinson, D C; Davies, A G; McPherson, M J; Wälti, C

    2016-06-15

    Biosensors with high sensitivity and short time-to-result that are capable of detecting biomarkers in body fluids such as serum are an important prerequisite for early diagnostics in modern healthcare provision. Here, we report the development of an electrochemical impedance-based sensor for the detection in serum of human interleukin-8 (IL-8), a pro-angiogenic chemokine implicated in a wide range of inflammatory diseases. The sensor employs a small and robust synthetic non-antibody capture protein based on a cystatin scaffold that displays high affinity for human IL-8 with a KD of 35 ± 10 nM and excellent ligand specificity. The change in the phase of the electrochemical impedance from the serum baseline, ∆θ(ƒ), measured at 0.1 Hz, was used as the measure for quantifying IL-8 concentration in the fluid. Optimal sensor signal was observed after 15 min incubation, and the sensor exhibited a linear response versus logarithm of IL-8 concentration from 900 fg/ml to 900 ng/ml. A detection limit of around 90 fg/ml, which is significantly lower than the basal clinical levels of 5-10 pg/ml, was observed. Our results are significant for the development of point-of-care and early diagnostics where high sensitivity and short time-to-results are essential. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Potential Role of Vascular Endothelial Growth Factor, Interleukin-8 and Monocyte Chemoattractant Protein-1 in Periodontal Diseases

    Directory of Open Access Journals (Sweden)

    En Lee

    2003-08-01

    Full Text Available Host-mediated immunoinflammatory pathways activated by bacteria lead to destruction of the periodontal connective tissues and alveolar bone. The objective of this study was to elucidate the activation of the inflammatory processes in periodontal disease by quantitative assessment of cytokines and periodontopathogens. Gingival crevicular fluids (GCF and subgingival plaque samples were collected from patients with chronic periodontitis and gingivitis and from periodontally healthy sites. Vascular endothelial growth factor (VEGF, monocyte chemoattractant protein-1 (MCP-1, and interleukin 8 (IL-8 in GCF were analyzed by enzyme-linked immunosorbent assay. Periodontopathogens, including Bacteroides forsythus, Campylobacter rectus, Porphyromonas gingivalis and Prevotella intermedia, were analyzed by immunofluorescence and dark-field microscopy. There was significantly more VEGF and IL-8 in chronic periodontitis and gingivitis sites than in periodontally healthy sites. There were significant positive correlations between the concentrations and total amounts of VEGF and IL-8 in chronic periodontitis and gingivitis sites, and between the levels of periodontopathogens and the total amounts of VEGF, MCP-1 and IL-8. These data indicate that inflammatory processes induced by periodontopathogens and the activation of certain cytokines (VEGF, MCP-1, IL-8 in periodontal diseases may be relevant to host-mediated destruction in chronic periodontitis.

  11. Decreased Pulmonary Function in School Children in Western Japan after Exposures to Asian Desert Dusts and Its Association with Interleukin-8

    Directory of Open Access Journals (Sweden)

    Masanari Watanabe

    2015-01-01

    Full Text Available The objective of the study was to investigate the influence of Asian dust storms (ADS on pulmonary function of school children and the relationship of this effect with interleukin-8. Morning peak expiratory flow (PEF was measured daily in 399 children from April to May 2012 and in 384 of these children from March to May 2013. The data were analyzed for an association between ADS events and PEF by linear mixed models. Interleukin-8 transcriptional activity was assessed in THP-G8 cells stimulated by airborne particles collected on ADS days. Seven ADS days were identified: April 23 and 24, 2012; March 8 to 10, 2013; and March 19 and 20, 2013. Changes in PEF after ADS exposure were −8.17 L/min (95% confidence interval, −11.40 to −4.93 in 2012 and −1.17 L/min (−4.07 to 1.74 in 2013, and there was a significant difference between 2012 and 2013. Interleukin-8 transcriptional activity was significantly higher in 2012 at 10.6±2.9-fold compared to 3.7±0.4 in March 8 to 10, 2013, and 2.3±0.2 in March 19 and 20, 2013. The influence of ADS events on pulmonary function of children differs with each ADS event and may be related to interleukin-8 production.

  12. Decreased Pulmonary Function in School Children in Western Japan after Exposures to Asian Desert Dusts and Its Association with Interleukin-8

    Science.gov (United States)

    Watanabe, Masanari; Kurai, Jun; Sano, Hiroyuki; Saito, Rumiko; Kimura, Yutaka; Aiba, Setsuya; Oshimura, Mitsuo; Yamasaki, Akira; Shimizu, Eiji

    2015-01-01

    The objective of the study was to investigate the influence of Asian dust storms (ADS) on pulmonary function of school children and the relationship of this effect with interleukin-8. Morning peak expiratory flow (PEF) was measured daily in 399 children from April to May 2012 and in 384 of these children from March to May 2013. The data were analyzed for an association between ADS events and PEF by linear mixed models. Interleukin-8 transcriptional activity was assessed in THP-G8 cells stimulated by airborne particles collected on ADS days. Seven ADS days were identified: April 23 and 24, 2012; March 8 to 10, 2013; and March 19 and 20, 2013. Changes in PEF after ADS exposure were −8.17 L/min (95% confidence interval, −11.40 to −4.93) in 2012 and −1.17 L/min (−4.07 to 1.74) in 2013, and there was a significant difference between 2012 and 2013. Interleukin-8 transcriptional activity was significantly higher in 2012 at 10.6 ± 2.9-fold compared to 3.7 ± 0.4 in March 8 to 10, 2013, and 2.3 ± 0.2 in March 19 and 20, 2013. The influence of ADS events on pulmonary function of children differs with each ADS event and may be related to interleukin-8 production. PMID:26060816

  13. Evidence that polymorphonuclear neutrophils infiltrate into the developing corpus luteum and promote angiogenesis with interleukin-8 in the cow

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    Shimizu Takashi

    2011-06-01

    Full Text Available Abstract Background After ovulation in the cow, the corpus luteum (CL rapidly develops within a few days with angiogenesis and progesterone production. CL formation resembles an inflammatory response due to the influx of immune cells. Neutrophils play a role in host defense and inflammation, and secrete chemoattractants to stimulate angiogenesis. We therefore hypothesized that neutrophils infiltrate in the developing CL from just after ovulation and may play a role in angiogenesis of the CL. Methods and Results Polymorphonuclear neutrophils (PMN were detected in CL tissue by Pas-staining, and interleukin-8 (IL-8, a neutrophil-specific chemoattractant was measured in supernatant of the CL tissue culture: considerable amounts of PMNs and the high level of IL-8 were observed during the early luteal phase (days 1-4 of the estrous cycle. PMNs and IL-8 were low levels in the mid and late luteal phases, but IL-8 was increased during luteal regression. The PMN migration in vitro was stimulated by the supernatant from the early CL but not from the mid CL, and this activity was inhibited by neutralizing with an anti-IL-8 antibody, indicating the major role of IL-8 in inducing active PMN migration in the early CL. Moreover, IL-8 stimulated proliferation of CL-derived endothelial cells (LECs, and both the supernatant of activated PMNs and IL-8 stimulated formation of capillary-like structures of LECs. Conclusion PMNs migrate into the early CL partially due to its major chemoattractant IL-8 produced at high levels in the CL, and PMNs is a potential regulator of angiogenesis together with IL-8 in developing CL in the cow.

  14. Evidence that polymorphonuclear neutrophils infiltrate into the developing corpus luteum and promote angiogenesis with interleukin-8 in the cow.

    Science.gov (United States)

    Jiemtaweeboon, Sineenard; Shirasuna, Koumei; Nitta, Akane; Kobayashi, Ayumi; Schuberth, Hans-Joachim; Shimizu, Takashi; Miyamoto, Akio

    2011-06-08

    After ovulation in the cow, the corpus luteum (CL) rapidly develops within a few days with angiogenesis and progesterone production. CL formation resembles an inflammatory response due to the influx of immune cells. Neutrophils play a role in host defense and inflammation, and secrete chemoattractants to stimulate angiogenesis. We therefore hypothesized that neutrophils infiltrate in the developing CL from just after ovulation and may play a role in angiogenesis of the CL. Polymorphonuclear neutrophils (PMN) were detected in CL tissue by Pas-staining, and interleukin-8 (IL-8, a neutrophil-specific chemoattractant) was measured in supernatant of the CL tissue culture: considerable amounts of PMNs and the high level of IL-8 were observed during the early luteal phase (days 1-4 of the estrous cycle). PMNs and IL-8 were low levels in the mid and late luteal phases, but IL-8 was increased during luteal regression. The PMN migration in vitro was stimulated by the supernatant from the early CL but not from the mid CL, and this activity was inhibited by neutralizing with an anti-IL-8 antibody, indicating the major role of IL-8 in inducing active PMN migration in the early CL. Moreover, IL-8 stimulated proliferation of CL-derived endothelial cells (LECs), and both the supernatant of activated PMNs and IL-8 stimulated formation of capillary-like structures of LECs. PMNs migrate into the early CL partially due to its major chemoattractant IL-8 produced at high levels in the CL, and PMNs is a potential regulator of angiogenesis together with IL-8 in developing CL in the cow.

  15. High concentrations of pepsin in bronchoalveolar lavage fluid from children with cystic fibrosis are associated with high interleukin-8 concentrations.

    LENUS (Irish Health Repository)

    McNally, P

    2012-02-01

    BACKGROUND: Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated. METHODS: This was a cross-sectional case-control study. BAL fluid was collected from individuals with CF (n=31) and healthy controls (n=7). Interleukin-8 (IL-8), pepsin, neutrophil numbers and neutrophil elastase activity levels were measured in all samples. Clinical, microbiological and lung function data were collected from medical notes. RESULTS: The pepsin concentration in BAL fluid was higher in the CF group than in controls (mean (SD) 24.4 (27.4) ng\\/ml vs 4.3 (4.0) ng\\/ml, p=0.03). Those with CF who had raised pepsin concentrations had higher levels of IL-8 in the BAL fluid than those with a concentration comparable to controls (3.7 (2.7) ng\\/ml vs 1.4 (0.9) ng\\/ml, p=0.004). Within the CF group there was a moderate positive correlation between pepsin concentration and IL-8 in BAL fluid (r=0.48, p=0.04). There was no association between BAL fluid pepsin concentrations and age, sex, body mass index z score, forced expiratory volume in 1 s or Pseudomonas aeruginosa colonisation status. CONCLUSIONS: Many children with CF have increased levels of pepsin in the BAL fluid compared with normal controls. Increased pepsin levels were associated with higher IL-8 concentrations in BAL fluid. These data suggest that aspiration of gastric contents occurs in a subset of patients with CF and is associated with more pronounced lung inflammation.

  16. Modulation of Interleukin-8 and staphylococcal flora by Avène hydrotherapy in patients suffering from chronic inflammatory dermatoses.

    Science.gov (United States)

    Casas, C; Ribet, V; Alvarez-Georges, S; Sibaud, V; Guerrero, D; Schmitt, A-M; Redoulès, D

    2011-02-01

    A number of studies argue in favour of an important role of microbial colonization, in particular of Staphylococcus aureus, in triggering atopic dermatitis (AD) flare-up and psoriasis, in particular through the superantigenic properties of toxins generated by S. aureus. The aim of this study was to assess the efficacy of a 3-week Avène hydrotherapy on the skin surface of patients suffering from psoriasis or atopic dermatitis. Skin samples were taken from healthy subjects or atopic (n = 18) or psoriatic patients (n = 39) undergoing hydrotherapy at Avène at the beginning (D0) and the end of treatment (D18). The severity of the dermatosis was evaluated according to SCORing Atopic Dermatitis (SCORAD) or Psoriasis Area Severity Index (PASI) scores at D0 and D18. Marker of inflammation interleukin 8 (IL-8), S. aureus colonization (protein A) and enterotoxins were assessed in skin samples using RT-PCR. At D0, significant differences were observed between healthy subjects and atopic or psoriatic patients in all the parameters evaluated (IL-8, protein A). At the end of the hydrotherapy, a significant decrease in SCORAD was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin D in patients with atopic dermatitis. Similarly, a significant decrease in PASI was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin N in patients with psoriasis. This study demonstrates the positive effects of Avène hydrotherapy on the skin of patients suffering from chronic dermatosis, with decreased inflammation and reduced colonization by S. aureus. © 2010 The Authors. JEADV © 2010 European Academy of Dermatology and Venereology.

  17. Phenylketonuria is not a risk factor for changes of inflammation status as assessed by interleukin 6 and interleukin 8 concentrations.

    Science.gov (United States)

    Mozrzymas, Renata; Duś-Żuchowska, Monika; Kałużny, Łukasz; Wenska-Chyży, Ewa; Walkowiak, Jarosław

    2016-01-01

    High oxidative stress and a reduced potential for free radical scavenging in phenylketonuria (PKU) patients, a phenomenon confirmed in a few studies, may lead to systemic chronic inflammation. The aim of this study was to compare the inflammation status, as assessed by interleukin 6 and interleukin 8 concentrations, in patients with PKU and in healthy controls. Twenty patients with classical PKU, aged 18-34 years and under dietary control, were enrolled in the study. The control group comprised of 20 healthy subjects matched for age and sex. Interleukin 6 and 8 levels were measured by enzyme-linked immunosorbent assay (ELISA) kits in all study participants. IL-6 concentrations in the study group ranged from 0.74 pg/ml to 1.34 pg/ml. No significant differences were found between IL-6 concentration between the study group and the control group (p = 0.989). IL-8 concentrations ranged from 17.56 pg/ml to 20.87 pg/ml. The obtained results of IL-8 levels did not differ significantly between the study group and control group (p = 0.192). No significant correlation was observed between Phe blood levels and IL-6 or IL-8 concentrations in the study group (ρ respectively: -0.225, 0.177). In a multivariate analysis, neither IL-6 nor IL-8 concentrations were correlated with sex, age, BMI and Phe levels. Phenylketonuria is not a risk factor for changes of inflammation status as assessed by IL-6 and IL-8 concentrations.

  18. Interleukin-8 production in response to tumor necrosis factor-alpha by cholesteatoma keratinocytes in cell culture.

    Science.gov (United States)

    Hilton, Christopher W; Ondrey, Frank G; Wuertz, Beverley R; Levine, Samuel C

    2011-02-01

    Keratinocytes harvested from acquired cholesteatoma and grown in cell culture will demonstrate increased interleukin-8 (IL-8) production in response to tumor necrosis factor (TNF)-alpha as compared with a control keratinocyte cell line. Immunohistochemical studies have identified IL-8 and TNF-alpha, mediators of bony destruction, in tissue samples of cholesteatoma. TNF-alpha stimulates IL-8 production in healthy epidermal keratinocyte cell lines. It is not known whether TNF-alpha stimulates IL-8 production in cultured cholesteatoma keratinocytes. Prospective controlled tissue culture experiment. Tissue from an acquired cholesteatoma was dissociated and grown in keratinocyte serum-free media for 8 weeks. Cholesteatoma keratinocytes and a control cell line of skin epidermal keratinocytes were treated with TNF-alpha. Conditioned media were harvested; production of IL-8 was measured by enzyme-linked immunosorbent assay, and cell counts were performed. At a zero concentration of TNF-alpha, mean production of IL-8 by cholesteatoma keratinocytes was 39,809 pg/mL/24hr/1 × 10(6) cells versus 1,907 pg/mL/24hr/1 × 10(6) cells from skin epidermal keratinocytes, a statistically significant difference (P alpha and a 2.44-fold increase in response to 20 pg/mL of TNF-alpha. The skin epidermal keratinocyte cell line demonstrated a 1.07- and 1.13-fold increase to respective concentrations of TNF-alpha. Cholesteatoma keratinocytes appear to retain cell signaling characteristics in vitro that distinguish them from skin epidermal keratinocytes. This finding may indicate that cholesteatoma keratinocytes undergo a change in behavior in vivo that is preserved after the cells are removed from the inflammatory environment of the middle ear. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  19. Relation Between Interleukin-1-β And Interleukin-8 Levels In Breast Milk (Colostrum) And Neonatal Physiological Jaundice

    International Nuclear Information System (INIS)

    Mohamed, A.A.; Moawad, A.T.; Marei, E.S.

    2011-01-01

    The immune system of neonates is influenced by maternal immunity during pregnancy and lactation. Breast-fed neonates have higher incidence of neonatal jaundice and higher level of total serum bilirubin than formula-fed infants. The aim of this study was to find a relationship between neonatal physiological jaundice and interleukin-1-beta (IL-1-β) and interleukin-8 (IL-8) in the colostrum of nursing mothers. Breast milk (colostrum) was collected from 45 nursing mothers of healthy full term neonates. The sharing mothers and their neonates were divided into two groups according to the presence of neonatal jaundice and the level of total serum bilirubin. All jaundiced neonates had total serum bilirubin level more than 12 mg/dl which appeared on the third postpartum day, all of them were breast-fed only. They were subjected to full history through clinical examination and laboratory investigations including determination of colostral levels of IL-1-β and IL-8, by ELISA, and determination of neonatal total serum bilirubin levels. This study revealed that mothers of neonates with physiological jaundice had higher concentrations of IL-1-β and IL-8 in their colostrums as compared with control group. Moreover, it displayed that total serum bilirubin level of jaundiced neonates was higher than its level in non-jaundiced neonates. There were significant correlations between IL- 1-β and IL-8 with mother's age in all groups, while there were inverse correlations between IL-1-β, IL-8 and gestational age of non- jaundiced neonates. Additionally, there was significant correlation between IL-1-β and IL-8 in the colostrum of all mothers enrolled in this study. On the other hand, no correlation was determined between cytokines IL-1-β, IL-8 and total serum bilirubin in all neonates sharing in this study. This study clearly demonstrated that the levels of immunomodulating agents such as cytokines IL-1-β and IL-8 were elevated in the colostrum of mothers with jaundiced neonates

  20. Parapoxvirus orf virus infection induces an increase in interleukin-8, tumour necrosis factor-α, and decorin in goat skin fibroblast cells

    Directory of Open Access Journals (Sweden)

    Wang Lingling

    2016-09-01

    Full Text Available Introduction: Orf virus (ORFV is a prototype Parapoxvirus species in the Poxviridae family that causes serious zoonotic infectious disease. Goat skin fibroblast (GSF cells are the major host targets of ORFV. Interleukin 8 (IL-8 and tumour necrosis factor (TNF-α are known to play a vital role in immune response during viral infections. However, the manner of variation over time of their level of expression in GSF cells remains unclear.

  1. Evidence of a role for mesothelial cell-derived interleukin 8 in the pathogenesis of asbestos-induced pleurisy in rabbits.

    OpenAIRE

    Boylan, A M; Rüegg, C; Kim, K J; Hébert, C A; Hoeffel, J M; Pytela, R; Sheppard, D; Goldstein, I M; Broaddus, V C

    1992-01-01

    Although acute asbestos-induced pleurisy is characterized by an influx of neutrophils, the identity of the factors that attract these cells to the pleural space and the source of the factors are unknown. We found that instillation of crocidolite asbestos into the pleural space of rabbits led to the appearance in pleural liquid of chemotactic activity for neutrophils, and that this chemotactic activity was inhibited significantly by a neutralizing antibody to human interleukin 8 (IL-8). Cultur...

  2. PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from human airway smooth muscle cells

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    Halayko Andrew J

    2009-09-01

    Full Text Available Abstract Background Airway smooth muscle contributes to the pathogenesis of pulmonary diseases by secreting inflammatory mediators such as interleukin-8 (IL-8. IL-8 production is in part regulated via activation of Gq-and Gs-coupled receptors. Here we study the role of the cyclic AMP (cAMP effectors protein kinase A (PKA and exchange proteins directly activated by cAMP (Epac1 and Epac2 in the bradykinin-induced IL-8 release from a human airway smooth muscle cell line and the underlying molecular mechanisms of this response. Methods IL-8 release was assessed via ELISA under basal condition and after stimulation with bradykinin alone or in combination with fenoterol, the Epac activators 8-pCPT-2'-O-Me-cAMP and Sp-8-pCPT-2'-O-Me-cAMPS, the PKA activator 6-Bnz-cAMP and the cGMP analog 8-pCPT-2'-O-Me-cGMP. Where indicated, cells were pre-incubated with the pharmacological inhibitors Clostridium difficile toxin B-1470 (GTPases, U0126 (extracellular signal-regulated kinases ERK1/2 and Rp-8-CPT-cAMPS (PKA. The specificity of the cyclic nucleotide analogs was confirmed by measuring phosphorylation of the PKA substrate vasodilator-stimulated phosphoprotein. GTP-loading of Rap1 and Rap2 was evaluated via pull-down technique. Expression of Rap1, Rap2, Epac1 and Epac2 was assessed via western blot. Downregulation of Epac protein expression was achieved by siRNA. Unpaired or paired two-tailed Student's t test was used. Results The β2-agonist fenoterol augmented release of IL-8 by bradykinin. The PKA activator 6-Bnz-cAMP and the Epac activator 8-pCPT-2'-O-Me-cAMP significantly increased bradykinin-induced IL-8 release. The hydrolysis-resistant Epac activator Sp-8-pCPT-2'-O-Me-cAMPS mimicked the effects of 8-pCPT-2'-O-Me-cAMP, whereas the negative control 8-pCPT-2'-O-Me-cGMP did not. Fenoterol, forskolin and 6-Bnz-cAMP induced VASP phosphorylation, which was diminished by the PKA inhibitor Rp-8-CPT-cAMPS. 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP induced GTP

  3. Hypo-responsiveness of interleukin-8 production in human embryonic epithelial intestine 407 cells independent of NF-κB pathway: New lessons from endotoxin and ribotoxic deoxynivalenol

    International Nuclear Information System (INIS)

    Moon, Yuseok; Yang, Hyun; Park, Seung-Hwan

    2008-01-01

    Mucosal epithelium senses external toxic insults and transmits the danger signals into the epithelial cells in order to activate a broad range of inflammatory responses. However, pre-exposure to the commensal endotoxins can induce inflammatory tolerance and maintain the homeostasis without excessive immune responses. We recently reported that ribotoxin deoxynivalenol (DON) and its derivatives elicited the pro-inflammatory response as the mucosal insults in human epithelial cells. Taking the knowledge into consideration, we tested the hypothesis that endotoxin pre-exposure can attenuate ribotoxin-induced epithelial interleukin-8 (IL-8) production via a tolerance mechanism. Pre-exposure to endotoxin repressed IL-8 release and its gene expression. However, inflammatory tolerance was not mediated by the attenuated NF-κB activation which has been generally recognized as the major mediator of LPS-mediated toll-like receptor (TLR) signaling pathway. Instead, pre-exposure to endotoxin was observed to trigger the delayed induction of peroxisome proliferator-activated receptor gamma (PPAR-γ) which contributed to the diminished IL-8 production in the human epithelial cells. Moreover, endogenous PPAR-γ agonist suppressed toxicant-mediated interleukin-8 production and IL-8 mRNA stability. Taken together, endotoxin induced hypo-production of pro-inflammatory cytokine IL-8 in the human epithelial cells, which was associated with the delayed activation of PPAR-γ expression by pre-existing endotoxin

  4. Maternal and Cord Blood Levels of Serum Amyloid A, C-Reactive Protein, Tumor Necrosis Factor-α, Interleukin -1β, and Interleukin-8 During and After Delivery

    Directory of Open Access Journals (Sweden)

    Luciane Marzzullo Cicarelli

    2005-01-01

    after delivery and try to correlate these proteins with tumor necrosis factor-α, interleukin -1β, and interleukin-8. Acute-phase proteins and cytokines were measured by ELISA in 24 healthy pregnant women undergoing vaginal delivery or Cesarean section. Cord blood samples in addition to maternal blood were collected. SAA and CRP reached the maximum maternal serum levels 24 hours after delivery, while cytokines remained constant over time. SAA and CRP were significantly higher in maternal serum than in newborn's (P<.001 at the moment of delivery. SAA and CRP, regardless of the type of delivery, reproduce the common pattern observed in most inflammatory conditions. Proinflammatory cytokine serum levels do not mirror the increase in SAA and CRP levels.

  5. Transmissible gastroenteritis virus nsp7 protein localized in the cytoplasm down-regulates interleukin 8 expression in porcine intestinal epithelial cell.

    Science.gov (United States)

    Zhang, Q; Huang, J L; Liang, Y B; He, Y P; Tong, D W; Xu, X G

    2018-01-01

    Transmissible gastroenteritis virus (TGEV) is an important pathogen in swine that is responsible for substantial economic losses. Previous studies suggest that the TGEV non-structural protein 7 (nsp7) plays an important role in the viral assembly process. However, the subcellular localization and other functions of the TGEV nsp7 protein are still unclear. In this study we have examined the subcellular localization and other functions of TGEV nsp7 protein through analysis of its effects on cell growth, cell cycle progression, interleukin 8 (IL-8) expression, and NF-κB activation. Our results showed that the nsp7 protein is localized in the cytoplasm and has no effect on intestinal epithelial cells (IECs) growth, cell cycle, and cyclin A expression. Further studies showed that TGEV nsp7 protein had no effect on GRP78 expression, could not induce endoplasmic reticulum (ER) stress and activate NF-κB activity. Interestingly, the IECs expressing nsp7 protein secreted lower levels of IL-8 than control cells. This is the first report to demonstrate the subcellular localization and novel functions of TGEV nsp7 protein. These findings provide novel information about the function of the poorly characterized TGEV non-structural protein 7.

  6. Inhibition of Toll-like receptor 2-mediated interleukin-8 production in Cystic Fibrosis airway epithelial cells via the alpha7-nicotinic acetylcholine receptor.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2010-01-01

    Cystic Fibrosis (CF) is an inherited disorder characterised by chronic inflammation of the airways. The lung manifestations of CF include colonization with Pseudomonas aeruginosa and Staphylococcus aureus leading to neutrophil-dominated airway inflammation and tissue damage. Inflammation in the CF lung is initiated by microbial components which activate the innate immune response via Toll-like receptors (TLRs), increasing airway epithelial cell production of proinflammatory mediators such as the neutrophil chemokine interleukin-8 (IL-8). Thus modulation of TLR function represents a therapeutic approach for CF. Nicotine is a naturally occurring plant alkaloid. Although it is negatively associated with cigarette smoking and cardiovascular damage, nicotine also has anti-inflammatory properties. Here we investigate the inhibitory capacity of nicotine against TLR2- and TLR4-induced IL-8 production by CFTE29o- airway epithelial cells, determine the role of alpha7-nAChR (nicotinic acetylcholine receptor) in these events, and provide data to support the potential use of safe nicotine analogues as anti-inflammatories for CF.

  7. Molecular cloning of interleukin-1β, interleukin-8, and tumor necrosis factor-α of bighorn sheep (Ovis canadensis) and comparison with those of other species.

    Science.gov (United States)

    Herndon, Caroline N; Dassanayake, Rohana P; Foreyt, William J; Srikumaran, Subramaniam

    2010-11-15

    The susceptibility to, and pathology induced by, Mannheimia haemolytica infection in bighorn sheep (BHS) and domestic sheep (DS) are distinctly different. Bighorn sheep are particularly susceptible to pneumonia caused by M. haemolytica, and the pneumonic lesions in infected BHS are more severe than those in DS. The molecular basis for this disparity has not been elucidated. Proinflammatory cytokines have been implicated in the pathogenesis of multiple lung diseases of humans and animals. It is possible that the enhanced pathology observed in the pneumonic lungs of M. haemolytica-infected BHS, in comparison to that of DS, is due to comparatively higher levels of proinflammatory cytokine expression in BHS. As the first step towards elucidating this concept, we have cloned and sequenced the cDNA encoding the cytokines interleukin-1β (IL-1β), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) of BHS. The cDNA of BHS IL-1β, IL-8, and TNF-α consists of 801, 306, and 705 base pairs encoding 266, 101, and 234 amino acids, respectively. The availability of cDNA encoding IL-1β, IL-8, and TNF-α of BHS should facilitate the elucidation of the role of these cytokines in the differential pathology induced by M. haemolytica infection in BHS and DS. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Reduction of Monocyte Chemoattractant Protein-1 and Interleukin-8 Levels by Ticlopidine in TNF-α Stimulated Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Chaur-Jong Hu

    2009-01-01

    Full Text Available Atherosclerosis and its associated complications represent major causes of morbidity and mortality in the industrialized or Western countries. Monocyte chemoattractant protein-1 (MCP-1 is critical for the initiating and developing of atherosclerotic lesions. Interleukin-8 (IL-8, a CXC chemokine, stimulates neutrophil chemotaxis. Ticlopidine is one of the antiplatelet drugs used to prevent thrombus formation relevant to the pathophysiology of atherothrombosis. In this study, we found that ticlopidine dose-dependently decreased the mRNA and protein levels of TNF-α-stimulated MCP-1, IL-8, and vascular cell adhesion molecule-1 (VCAM-1 in human umbilical vein endothelial cells (HUVECs. Ticlopidine declined U937 cells adhesion and chemotaxis as compared to TNF-α stimulated alone. Furthermore, the inhibitory effects were neither due to decreased HUVEC viability, nor through NF-kB inhibition. These results suggest that ticlopidine decreased TNF-α induced MCP-1, IL-8, and VCAM-1 levels in HUVECs, and monocyte adhesion. Therefore, the data provide additional therapeutic machinery of ticlopidine in treatment and prevention of atherosclerosis.

  9. Differential regulation of angiogenic cellular processes and claudin-5 by histamine and VEGF via PI3K-signaling, transcription factor SNAI2 and interleukin-8.

    Science.gov (United States)

    Laakkonen, Johanna P; Lappalainen, Jari P; Theelen, Thomas L; Toivanen, Pyry I; Nieminen, Tiina; Jauhiainen, Suvi; Kaikkonen, Minna U; Sluimer, Judith C; Ylä-Herttuala, Seppo

    2017-02-01

    Histamine and vascular endothelial growth factor A (VEGF) are central regulators in vascular pathologies. Their gene regulation leading to vascular remodeling has remained obscure. In this study, EC regulation mechanisms of histamine and VEGF were compared by RNA sequencing of primary endothelial cells (ECs), functional in vitro assays and in vivo permeability mice model. By RNA sequencing, similar transcriptional alterations of genes involved in activation of primary ECs, cell proliferation and adhesion were observed between histamine and VEGF. Seventy-six commonly regulated genes were found, representing ~53% of all VEGF-regulated transcripts and ~26% of all histamine-regulated transcripts. Both factors regulated tight junction formation and expression of pro-angiogenic transcription factors (TFs) affecting EC survival, migration and tube formation. Novel claudin-5 upstream regulatory genes were identified. VEGF was demonstrated to regulate expression of SNAI2, whereas pro-angiogenic TFs NR4A1, MYCN and RCAN1 were regulated by both histamine and VEGF. Claudin-5 was shown to be regulated VEGFR2/PI3K-Akt dependently by VEGF and PI3K-Akt independently by histamine. Interleukin-8 was shown to downregulate claudin-5 by histamine. Additionally, SNAI2, NR4A1 and MYCN were shown to mediate EC survival, migration and tube formation and to regulate expression of claudin-5. Further systemic delivery of VEGF and histamine was shown to induce a fast vascular hyperpermeability response in intact vasculature of C57/Bl6 mice followed by regulation of NR4A1 and MYCN. Our study identifies novel claudin-5 upstream regulatory genes of histamine and VEGF that induce cellular angiogenic processes. Our results increase knowledge of angiogenic EC phenotype and provide novel treatment targets for vascular pathologies.

  10. Inhibition of Lipopolysaccharide-Induced Interleukin 8 in Human Adenocarcinoma Cell Line HT-29 by Spore Probiotics: B. coagulans and B. subtilis (natto).

    Science.gov (United States)

    Azimirad, Masoumeh; Alebouyeh, Masoud; Naji, Tahereh

    2017-03-01

    Probiotics are used as a treatment for different intestinal disorders. They confer health benefits by different ways. This study was aimed to investigate immunomodulatory effect of Bacillus probiotic spores on the production of lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) in HT-29 intestinal epithelial cells. Differentiated intestinal epithelial cell line was used as a model for the study of colonization of purified spores (Bacillus subtilis (natto) and B. coagulans) and their anti-inflammatory effects. MTT assay and trypan blue staining were used for the detection of optimal concentration of the purified spores and LPS. Pre-treatment assay was done by treatment of the cells with the purified spores for 2 h, followed by challenges with LPS for 3 and 18 h. Post-treatment assay was done by initial treatment of the cells with LPS for 18 h, followed by the spores for 3 and 6 h. Levels of IL-8 secretion and its mRNA expression were measured by ELISA and relative Q real-time PCR. Our results showed similar rates of adherence to intestinal epithelial cells by the spore probiotics, while displaying no cytotoxic effect. In the pre-treatment assay, a significant decrease in IL-8, at both protein and mRNA levels, was measured for B. coagulans spores after the addition of LPS, which was higher than those observed for Bacillus subtilis (natto) spores. In the post-treatment assay, while Bacillus subtilis (but not B. coagulans) diminished the LPS-stimulated IL-8 levels after 3 h of incubation, the inhibitory effect was not constant. In conclusion, ability of Bacillus spore probiotics for adherence to intestinal epithelial cell and their anti-inflammatory effects, through interference with LPS/IL-8 signaling, was shown in this study. Further studies are needed to characterize responsible bacterial compounds associated with these effects.

  11. Differential expression of interleukin-8 by polymorphonuclear leukocytes of two closely related species, Ovis canadensis and Ovis aries, in response to Mannheimia haemolytica infection.

    Science.gov (United States)

    Herndon, Caroline N; Foreyt, William J; Srikumaran, Subramaniam

    2010-08-01

    The pneumonic lesions and mortality caused by Mannheimia haemolytica in bighorn sheep (BHS; Ovis canadensis) are more severe than those in the related species, domestic sheep (DS; Ovis aries), under both natural and experimental conditions. Leukotoxin (Lkt) and lipopolysaccharide (LPS) are the most important virulence factors of this organism. One hallmark of pathogenesis of pneumonia is the influx of polymorphonuclear leukocytes (PMNs) into the lungs. Lkt-induced cytolysis of PMNs results in the release of cytotoxic compounds capable of damaging lung tissue. Interleukin-8 (IL-8) is a potent PMN chemoattractant. The objective of the present study was to determine if there is differential expression of IL-8 by the macrophages and PMNs of BHS and DS in response to M. haemolytica. Macrophages and PMNs of BHS and DS were stimulated with heat-killed M. haemolytica or LPS. IL-8 expression by the cells was measured by enzyme-linked immunosorbent assays and real-time reverse transcription-PCR (RT-PCR). The PMNs of BHS expressed severalfold higher levels of IL-8 than those of DS upon stimulation. Lesional lung tissue of M. haemolytica-infected BHS contained significantly higher levels of IL-8 than nonlesional tissue. The bronchoalveolar lavage (BAL) fluid of infected BHS also contained higher levels of IL-8 than that of infected DS. Depletion of IL-8 reduced migration of PMNs toward BAL fluid by approximately 50%, indicating that IL-8 is integral to PMN recruitment to the lung during M. haemolytica infection. Excessive production of IL-8, enhanced recruitment of PMNs, and PMN lysis by Lkt are likely responsible for the severity of the lung lesions in M. haemolytica-infected BHS.

  12. Gingival crevicular fluid interleukin-8 and lipoxin A4 levels of smokers and nonsmokers with different periodontal status: a cross-sectional study.

    Science.gov (United States)

    Lütfioğlu, M; Aydoğdu, A; Sakallioğlu, E E; Alaçam, H; Pamuk, F

    2016-08-01

    Smoking is an important risk factor for periodontal disease and effects the pathogenesis of the disease. This study evaluated the impact of smoking on gingival crevicular fluid interleukin-8 (IL-8) and lipoxin A4 (LxA4 ) levels in patients with and without periodontal disease. A total of 122 participants were grouped as follows: smokers with generalized aggressive periodontitis (S-GAgP, n = 15); smokers with chronic periodontitis (S-CP, n = 17); smokers with gingivitis (SG, n = 15); smokers classified as periodontally healthy (SH, n = 15); nonsmokers with generalized aggressive periodontitis (N-GAgP, n = 15); nonsmokers with chronic periodontitis (N-CP, n = 15); nonsmokers with gingivitis (NG, n = 15); and nonsmokers classified as periodontally healthy (NH, n = 15). Gingival index, plaque index, probing pocket depth and clinical attachment level were recorded. Gingival crevicular fluid IL-8 and LxA4 levels were analyzed by ELISA. Gingival crevicular fluid IL-8 levels varied among groups, as follows: S-GAgP>S-CP>SG>SH and N-GAgP>N-CP>NG>NH. The gingival crevicular fluid IL-8 levels were significantly higher in the S-GAgP group compared with the N-GAgP group and in the S-CP group compared with the N-CP group (p 0.05). Gingival crevicular fluid LxA4 levels also varied among groups, but in an inverse direction when compared with the IL-8 levels, as follows: S-GAgP 0.05). The study findings suggest that the observed increases in gingival crevicular fluid IL-8 levels and decreases in gingival crevicular fluid LxA4 levels reflect changes in immune and inflammatory responses that occur as a result of smoking. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Thyrotropin receptor and CD40 mediate interleukin-8 expression in fibrocytes: implications for thyroid-associated ophthalmopathy (an American Ophthalmological Society thesis).

    Science.gov (United States)

    Douglas, Raymond S; Mester, Tünde; Ginter, Anna; Kim, Denise S

    2014-01-01

    To better understand the pathogenesis of thyroid-associated orbitopathy (TAO) through elucidating the role of thyrotropin receptor (TSHR) and CD40 in the expression of interleukin-8 (IL-8) in peripheral blood fibrocytes. Fibrocytes infiltrate the orbit of patients with TAO, where they differentiate into fibroblasts. Fibrocyte precursors occur with increased frequency in the peripheral blood expressing TSHR and CD40 in TAO patients. We hypothesize that in vitro derived fibrocytes and peripheral blood fibrocyte precursors express proinflammatory chemoattractant molecules including IL-8 initiated by TSHR and CD40 signaling. Since nearly all TAO patients express activating antibodies to TSHR, this is particularly relevant for activation of peripheral blood fibrocytes. TSHR and CD40 expression on peripheral blood fibrocytes was determined by flow cytometry. IL-8 RNA was quantitated by real-time polymerase chain reaction. IL-8 protein production was measured by Luminex and flow cytometry. Thyroid-stimulating hormone and CD40 ligand-stimulated phosphorylation of Akt in peripheral blood fibrocytes was studied by flow cytometry. Both TSHR- and CD40-mediated signaling lead to IL-8 expression in mature fibrocytes. Fibrocyte precursors assayed directly from circulating peripheral blood demonstrate intracellular IL-8 expression with addition of thyroid-stimulating hormone or CD40 ligand. TSHR- and CD40-induced IL-8 production is mediated by Akt phosphorylation. Peripheral blood TSHR(+) and CD40(+) fibrocytes express IL-8 and may promote the recruitment of inflammatory cells, mitogenesis, and tissue remodeling in TAO. TSHR- and CD40-mediated IL-8 signaling is mediated by Akt. Delineating the molecular mechanisms of fibrocyte immune function may provide potential therapeutic targets for TAO.

  14. Constructing disease-specific gene networks using pair-wise relevance metric: application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements.

    Science.gov (United States)

    Jiang, Wei; Li, Xia; Rao, Shaoqi; Wang, Lihong; Du, Lei; Li, Chuanxing; Wu, Chao; Wang, Hongzhi; Wang, Yadong; Yang, Baofeng

    2008-08-10

    With the advance of large-scale omics technologies, it is now feasible to reversely engineer the underlying genetic networks that describe the complex interplays of molecular elements that lead to complex diseases. Current networking approaches are mainly focusing on building genetic networks at large without probing the interaction mechanisms specific to a physiological or disease condition. The aim of this study was thus to develop such a novel networking approach based on the relevance concept, which is ideal to reveal integrative effects of multiple genes in the underlying genetic circuit for complex diseases. The approach started with identification of multiple disease pathways, called a gene forest, in which the genes extracted from the decision forest constructed by supervised learning of the genome-wide transcriptional profiles for patients and normal samples. Based on the newly identified disease mechanisms, a novel pair-wise relevance metric, adjusted frequency value, was used to define the degree of genetic relationship between two molecular determinants. We applied the proposed method to analyze a publicly available microarray dataset for colon cancer. The results demonstrated that the colon cancer-specific gene network captured the most important genetic interactions in several cellular processes, such as proliferation, apoptosis, differentiation, mitogenesis and immunity, which are known to be pivotal for tumourigenesis. Further analysis of the topological architecture of the network identified three known hub cancer genes [interleukin 8 (IL8) (p approximately 0), desmin (DES) (p = 2.71 x 10(-6)) and enolase 1 (ENO1) (p = 4.19 x 10(-5))], while two novel hub genes [RNA binding motif protein 9 (RBM9) (p = 1.50 x 10(-4)) and ribosomal protein L30 (RPL30) (p = 1.50 x 10(-4))] may define new central elements in the gene network specific to colon cancer. Gene Ontology (GO) based analysis of the colon cancer-specific gene network and the sub-network that

  15. Constructing disease-specific gene networks using pair-wise relevance metric: Application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements

    Directory of Open Access Journals (Sweden)

    Jiang Wei

    2008-08-01

    Full Text Available Abstract Background With the advance of large-scale omics technologies, it is now feasible to reversely engineer the underlying genetic networks that describe the complex interplays of molecular elements that lead to complex diseases. Current networking approaches are mainly focusing on building genetic networks at large without probing the interaction mechanisms specific to a physiological or disease condition. The aim of this study was thus to develop such a novel networking approach based on the relevance concept, which is ideal to reveal integrative effects of multiple genes in the underlying genetic circuit for complex diseases. Results The approach started with identification of multiple disease pathways, called a gene forest, in which the genes extracted from the decision forest constructed by supervised learning of the genome-wide transcriptional profiles for patients and normal samples. Based on the newly identified disease mechanisms, a novel pair-wise relevance metric, adjusted frequency value, was used to define the degree of genetic relationship between two molecular determinants. We applied the proposed method to analyze a publicly available microarray dataset for colon cancer. The results demonstrated that the colon cancer-specific gene network captured the most important genetic interactions in several cellular processes, such as proliferation, apoptosis, differentiation, mitogenesis and immunity, which are known to be pivotal for tumourigenesis. Further analysis of the topological architecture of the network identified three known hub cancer genes [interleukin 8 (IL8 (p ≈ 0, desmin (DES (p = 2.71 × 10-6 and enolase 1 (ENO1 (p = 4.19 × 10-5], while two novel hub genes [RNA binding motif protein 9 (RBM9 (p = 1.50 × 10-4 and ribosomal protein L30 (RPL30 (p = 1.50 × 10-4] may define new central elements in the gene network specific to colon cancer. Gene Ontology (GO based analysis of the colon cancer-specific gene network and

  16. Depletion of intrinsic expression of Interleukin-8 in prostate cancer cells causes cell cycle arrest, spontaneous apoptosis and increases the efficacy of chemotherapeutic drugs

    Directory of Open Access Journals (Sweden)

    Lokeshwar Bal L

    2009-07-01

    Full Text Available Abstract Background The progression of all cancers is characterized by increased-cell proliferation and decreased-apoptosis. The androgen-independent prostate cancer (AIPC is the terminal stage of the disease. Many chemokines and cytokines are suspects to cause this increased tumor cell survival that ultimately leads to resistance to therapy and demise of the host. The AIPC cells, but not androgen-responsive cells, constitutively express abundant amount of the pro-inflammatory chemokine, Interleukin-8 (IL-8. The mechanism of IL-8 mediated survival and therapeutic resistance in AIPC cells is unclear at present. The purpose of this report is to show the pervasive role of IL-8 in malignant progression of androgen-independent prostate cancer (AIPC and to provide a potential new therapeutic avenue, using RNA interference. Results The functional consequence of IL-8 depletion in AIPC cells was investigated by RNA interference in two IL-8 secreting AIPC cell lines, PC-3 and DU145. The non-IL-8 secreting LNCaP and LAPC-4 cells served as controls. Cells were transfected with RISC-free siRNA (control or validated-pool of IL-8 siRNA. Transfection with 50 nM IL-8 siRNA caused >95% depletion of IL-8 mRNA and >92% decrease in IL-8 protein. This reduction in IL-8 led to cell cycle arrest at G1/S boundary and decreases in cell cycle-regulated proteins: Cyclin D1 and Cyclin B1 (both decreased >50% and inhibition of ERK1/2 activity by >50%. Further, the spontaneous apoptosis was increased by >43% in IL-8 depleted cells, evidenced by increases in caspase-9 activation and cleaved-PARP. IL-8 depletion caused significant decreases in anti-apoptotic proteins, BCL-2, BCL-xL due to decrease in both mRNA and post-translational stability, and increased levels of pro-apoptotic BAX and BAD proteins. More significantly, depletion of intracellular IL-8 increased the cytotoxic activity of multiple chemotherapeutic drugs. Specifically, the cytotoxicity of Docetaxel

  17. Endothelial immunomediated reactivity in acute cardiac ischaemia: Role of endothelin 1, interleukin 8 and NT-proBNP in patients affected by unstable angina pectoris.

    Science.gov (United States)

    Caroselli, Costantino; De Rosa, Rosario; Tanzi, Pietro; Rigatelli, Alberto; Bruno, Guglielmo

    2016-09-01

    The role of endothelium in the progression of atheromasic disease has already been demonstrated. Endothelin-1 (ET-1) is released from endothelial cells during acute and chronic vascular damage and it appears to be the strongest vasoconstrictor agent known.The aim of this study is to investigate the amount of endothelial damage in patients with unstable angina (UA), as defined by serum levels of ET-1, to verify a possible correlation with increased ischaemic damage by evaluation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin 8 (IL-8) levels.Serum levels of ET-1, IL-8 and NT-proBNP obtained from 10 patients affected by low-risk UA were compared to those belonging to eight healthy subjects. In order to compare the laboratory data pertaining to the two populations, a Student's t-test and a Mann-Whitney U test were performed.Levels of ET-1, IL-8 and NT-proBNP in samples of peripheral blood of patients affected by UA were significantly elevated, compared with those of the control group. The linear correlation analysis demonstrated a positive and significant correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP in subjects affected by UA.Early elevated levels of ET-1, IL-8 and NT-proBNP in patients with UA show a coexistence between ischaemic insults and endothelial damages. A positive and significant linear correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP confirms that an increased ischaemic insult is correlated to inflammation signs and endothelium damage signs.In patients with UA, ischaemia is always associated with a systemic immuno-mediated activity induced by acute endothelial damage. We suggest early administration of ET-1-selective receptor blockers and anti-inflammatory drugs. © The Author(s) 2015.

  18. Comparison of CCL28, interleukin-8, interleukin-1β and tumor necrosis factor-alpha in subjects with gingivitis, chronic periodontitis and generalized aggressive periodontitis.

    Science.gov (United States)

    Ertugrul, A S; Sahin, H; Dikilitas, A; Alpaslan, N; Bozoglan, A

    2013-02-01

    Cytokines produced by various cells are strong local mediators of inflammation. Mucosa-associated epithelial chemokine (CCL28), interleukin-8 (IL-8), interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) are major cytokines that play important roles in the periodontal inflammatory process. In this study we aimed to compare the levels of CCL28, IL-8, IL-1β and TNF-α in the gingival crevicular fluid of both periodontally healthy subjects and in subjects diagnosed with gingivitis, chronic periodontitis and generalized aggressive periodontitis. A total of 84 subjects participated in the study: 21 subjects had gingivitis, 21 subjects had chronic periodontitis, 21 subjects had generalized aggressive periodontitis and 21 were periodontally healthy. The levels of CCL28, IL-8, IL-1β and TNF-α were analyzed using enzyme-linked immune sorbent assay (ELISA). The total levels of CCL28 and IL-8 in the gingival crevicular fluid of the generalized aggressive periodontitis group (324.74 ± 42.62 pg/30 s, 487.62 ± 49.21 pg/30 s) were significantly higher than those of the chronic periodontitis group (268.81 ± 28.64 pg/30 s, 423.65 ± 35.24 pg/30 s), the gingivitis group (146.35 ± 17.46 pg/30 s, 310.24 ± 48.20 pg/30 s) and the periodontally healthy group (92.46 ± 22.04 pg/30 s, 148.41 ± 24.64 pg/30 s). Similarly, the total levels of IL-1β and TNF-α in the generalized aggressive periodontitis group (110.23 ± 9.20 pg/30 s, 1284.46 ± 86.32 pg/30 s) were significantly higher than those in the chronic periodontitis group (423.65 ± 35.24 pg/30 s, 82.64 ± 9.12 pg/30 s), the gingivitis group (52.10 ± 7.15 pg/30 s, 824.24 ± 44.68 pg/30 s) and the periodontally healthy group (36.44 ± 8.86 pg/30 s, 628.26 ± 34.61 pg/30 s). CCL28, IL-8, IL-1β and TNF-α may play key roles in the host response to inflammation in periodontal diseases. As the severity of periodontal diseases increases, destruction of periodontal tissues also increases. Inflammation is one among

  19. Relationship of serum levels of interleukin 6, interleukin 8, and C-reactive protein with forced expiratory volume in first second in patients with mustard lung and chronic obstructive pulmonary diseases: systematic review and meta-analysis.

    Science.gov (United States)

    Shahriary, Alireza; Panahi, Yunes; Shirali, Saeed; Rahmani, Hossein

    2017-06-01

    The chronic systemic inflammation is a result of releasing inflammatory cytokines from the cells relating to the body immunity system and chronic activation of the innate immunity system. To evaluate the relationship among serum levels of interleukin 6 (IL-6), interleukin 8 (IL-8), C-reactive protein (CRP) with forced expiratory volume in 1 st s (FEV 1 ) in patients with mustard lung (ML) and chronic obstructive pulmonary diseases (COPD). A published literature search was performed through SID, web of science, ISI, Science Direct, Scopus, Medline, and PubMed databases for articles published in English. The correlation coefficient ( r ) and 95% confidence intervals (95% CIs) were calculated using random or fixed effects models. Heterogeneity was assessed using χ 2 and I 2 statistics. In total, 4 published studies were included in the final analysis. Using the random-effect model, meta-analysis showed that the r was -0.052 (95% CI: -0.14-0.049, p = 0.28) at serum level of IL-8, serum levels of CRP and FEV 1 in these results were r = -0.13, p = 0.012, serum levels of tumor necrosis factor (TNF) and FEV 1 levels were r = -0.39, p = 0.03 in the conducted studies on mustard lung patients. The IL-6 serum level was explored in COPD patients. The results of the given studies in these patients are r = -0.006, 95% CI: -0.37-0.15, and p = 0.44. In this meta-analysis, there was evidence that serum levels of CRP and TNF have been significantly increased in chronic obstructive pulmonary diseases compared to the healthy control group, which signifies the presence of systemic inflammation in ML and COPD patients.

  20. Oral supplementation of turmeric attenuates proteinuria, transforming growth factor-β and interleukin-8 levels in patients with overt type 2 diabetic nephropathy: a randomized, double-blind and placebo-controlled study.

    Science.gov (United States)

    Khajehdehi, Parviz; Pakfetrat, Maryam; Javidnia, Katayoun; Azad, Fariborz; Malekmakan, Leila; Nasab, Mahshid Hashemi; Dehghanzadeh, Gholamreza

    2011-11-01

    End-stage renal disease (ESRD) due to type 2 diabetic nephropathy is a very common condition which is increasing in prevalence, and is associated with high global levels of mortality and morbidity. Both proteinuria and transforming growth factor-β (TGF-β) may contribute to the development of ESRD in patients with diabetic nephropathy. Experimental studies indicate that turmeric improves diabetic nephropathy by suppressing TGF-β. Therefore, this study investigated the effects of turmeric on serum and urinary TGF-β, interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α), as well as proteinuria, in patients with overt type 2 diabetic nephropathy. A randomized, double-blind and placebo-controlled study was carried out in the Diabetes Clinic of the Outpatient Department of Shiraz University of Medical Sciences on 40 patients with overt type 2 diabetic nephropathy, randomized into a trial group (n = 20) and a control group (n = 20). Each patient in the trial group received one capsule with each meal containing 500 mg turmeric, of which 22.1 mg was the active ingredient curcumin (three capsules daily) for 2 months. The control group received three capsules identical in colour and size containing starch for the same 2 months. Serum levels of TGF-β and IL-8 and urinary protein excretion and IL-8 decreased significantly comparing the pre- and post-turmeric supplementation values. No adverse effects related to turmeric supplementation were observed during the trial. Short-term turmeric supplementation can attenuate proteinuria, TGF-β and IL-8 in patients with overt type 2 diabetic nephropathy and can be administered as a safe adjuvant therapy for these patients.

  1. Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: Stimulation of interleukin-8 secretion, potentiation of interleukin-1β effect and increase in the transepithelial passage of commensal bacteria

    International Nuclear Information System (INIS)

    Maresca, Marc; Yahi, Nouara; Younes-Sakr, Lama; Boyron, Marilyn; Caporiccio, Bertrand; Fantini, Jacques

    2008-01-01

    Mycotoxins are fungal secondary metabolites responsible of food-mediated intoxication in animals and humans. Deoxynivalenol, ochratoxin A and patulin are the best known enteropathogenic mycotoxins able to alter intestinal functions resulting in malnutrition, diarrhea, vomiting and intestinal inflammation in vivo. Although their effects on intestinal barrier and transport activities have been extensively characterized, the mechanisms responsible for their pro-inflammatory effect are still poorly understood. Here we investigated if mycotoxin-induced intestinal inflammation results from a direct and/or indirect pro-inflammatory activity of these mycotoxins on human intestinal epithelial cells, using differentiated Caco-2 cells as model and interleukin 8 (IL-8) as an indicator of intestinal inflammation. Deoxynivalenol was the only mycotoxin able to directly increase IL-8 secretion (10- to 15-fold increase). We also investigated if these mycotoxins could indirectly stimulate IL-8 secretion through: (i) a modulation of the action of pro-inflammatory molecules such as the interleukin-1beta (IL-1β), and/or (ii) an increase in the transepithelial passage of non-invasive commensal Escherichia coli. We found that deoxynivalenol, ochratoxin A and patulin all potentiated the effect of IL-1β on IL-8 secretion (ranging from 35% to 138% increase) and increased the transepithelial passage of commensal bacteria (ranging from 12- to 1544-fold increase). In addition to potentially exacerbate established intestinal inflammation, these mycotoxins may thus participate in the induction of sepsis and intestinal inflammation in vivo. Taken together, our results suggest that the pro-inflammatory activity of enteropathogenic mycotoxins is mediated by both direct and indirect effects

  2. Interleukin-8, CXCL1, and MicroRNA miR-146a Responses to Probiotic Escherichia coli Nissle 1917 and Enteropathogenic E. coli in Human Intestinal Epithelial T84 and Monocytic THP-1 Cells after Apical or Basolateral Infection.

    Science.gov (United States)

    Sabharwal, Harshana; Cichon, Christoph; Ölschläger, Tobias A; Sonnenborn, Ulrich; Schmidt, M Alexander

    2016-09-01

    Bacterium-host interactions in the gut proceed via directly contacted epithelial cells, the host's immune system, and a plethora of bacterial factors. Here we characterized and compared exemplary cytokine and microRNA (miRNA) responses of human epithelial and THP-1 cells toward the prototype enteropathogenic Escherichia coli (EPEC) strain E2348/69 (O127:H6) and the probiotic strain Escherichia coli Nissle 1917 (EcN) (O6:K5:H1). Human T84 and THP-1 cells were used as cell culture-based model systems for epithelial and monocytic cells. Polarized T84 monolayers were infected apically or basolaterally. Bacterial challenges from the basolateral side resulted in more pronounced cytokine and miRNA responses than those observed for apical side infections. Interestingly, the probiotic EcN also caused a pronounced transcriptional increase of proinflammatory CXCL1 and interleukin-8 (IL-8) levels when human T84 epithelial cells were infected from the basolateral side. miR-146a, which is known to regulate adaptor molecules in Toll-like receptor (TLR)/NF-κB signaling, was found to be differentially regulated in THP-1 cells between probiotic and pathogenic bacteria. To assess the roles of flagella and flagellin, we employed several flagellin mutants of EcN. EcN flagellin mutants induced reduced IL-8 as well as CXCL1 responses in T84 cells, suggesting that flagellin is an inducer of this cytokine response. Following infection with an EPEC type 3 secretion system (T3SS) mutant, we observed increased IL-8 and CXCL1 transcription in T84 and THP-1 cells compared to that in wild-type EPEC. This study emphasizes the differential induction of miR-146a by pathogenic and probiotic E. coli strains in epithelial and immune cells as well as a loss of probiotic properties in EcN interacting with cells from the basolateral side. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. СHARACTERISTICS OF THE HEART FATTY ACID-BINDING PROTEIN, INTERLEUKIN-6 AND INTERLEUKIN-8 AS ALTERNATIVE MARKERS OF DIABETIC NEPHROPATHY PROGRESSION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Yu. A. Ryzhikova

    2015-01-01

    Full Text Available The aim of this work was to study the levels of the heart fatty acid-binding protein (h-FABP, interleukin6 (IL-6 and interleukin-8 (IL-8, in diabetic nephropathy (DN in patients with type 1 diabetes mellitus (T1DM. Material and methods. We examined 87 patients aged 18 to 54 with T1DM within the study group. 30 patients with type 1 diabetes were diagnosed with normoalbuminuria, 29 patients – with microalbuminuria and 28 patients – with proteinuria. The control group consisted of 24 healthy donor aged 22 to 29. The comparison group included 22 patients aged 20 to 42 with verified diagnosis of essential arterial hypertension (AH without carbohydrate metabolism disorders. The daily urinary albumin excretion was determined by immunoturbidimetric technique. 30 patients with type 1 diabetes were diagnosed with normoalbuminuria, 29 patients – with microalbuminuria and 28 patients with proteinuria.Calculation of glomerular filtration rate was performed according to the Hoek formula with the use of cystatinС serum concentrations. Contents of h-FABP, IL-6 and cystatin C in serum and h-FABP, IL-8 inurine were determined by enzyme-linked immunosorbent assay. Results. Analysis of the h-FABP content in serum showed that the concentration of this marker in individuals with T1DM was higher than in patients of the control group and the comparison group. Analysis of the h-FABP content in the urine revealed that individuals with essential hypertension showed an increased level of h-FABP while patients with T1DM demonstrated the highest concentration of h-FABP. The concentration of IL-6 inindividuals with T1DM and in individuals with AH significantly exceeded the control values. The contents of h-FABP and IL-6 inserum and h-FABP and IL-8 inurine increased with the progression of DN and reached maximum in individuals of the proteinuria subgroup. At the same time, the levels of h-FABP and IL-8 inthe urine of patients in the microalbuminuria (MAU subgroup were

  4. Interleukin-8 A Marker of Disease Progression and Therapeutic ...

    African Journals Online (AJOL)

    8 was determined in HIV infected subjects at the Lagos university Teaching Hospital, Lagos, Nigeria. These are subjects on anti-retroviral treatment, freshly diagnosed treatment naïve HIV positive individuals, and non-HIV infected controls ...

  5. Evaluation of Interleukin 8 gene polymorphism for predicting ...

    African Journals Online (AJOL)

    Rajasree Shanmuganathan

    2016-07-09

    Jul 9, 2016 ... Hacking D, Knight JC, Rockett K, Brown H, Frampton J, et al. Increased in vivo transcription of an IL-8 haplotype associated · with respiratory syncytial virus disease-susceptibility. Genes · Immun 2004;5:274–82. 10. Michaud DS, Daugherty SE, Berndt SI, Platz EA, Yeager M, et al. Genetic polymorphisms of ...

  6. RESEARCH ARTICLE Interleukin 8 in progression of hormone ...

    Indian Academy of Sciences (India)

    24

    The study included 91 early stage breast cancer patients (clinical stadium I/II) with known clinicopathological .... et al 2012) as well as colorectal cancer patients (Biasi et al 2012). Reis et al first indicated the ... cancer, in contrast to the previously accepted hypothesis that IL8 expression is important feature that exclusively ...

  7. Ozone Enhances Diesel Exhaust Particles (DEP-Induced Interleukin-8 (IL-8 Gene Expression in Human Airway Epithelial Cells through Activation of Nuclear Factors- κB (NF-κB and IL-6 (NF-IL6

    Directory of Open Access Journals (Sweden)

    James Kelley

    2005-12-01

    Full Text Available Ozone, a highly reactive oxidant gas is a major component of photochemical smog. As an inhaled toxicant, ozone induces its adverse effects mainly on the lung. Inhalation of particulate matter has been reported to cause airway inflammation in humans and animals. Furthermore, epidemiological evidence has indicated that exposure to particulate matter (PM2.5-10, including diesel exhaust particles (DEP has been correlated with increased acute and chronic respiratory morbidity and exacerbation of asthma. Previously, exposure to ozone or particulate matter and their effect on the lung have been addressed as separate environmental problems. Ozone and particulate matter may be chemically coupled in the ambient air. In the present study we determined whether ozone exposure enhances DEP effect on interleukin-8 (IL-8 gene expression in human airway epithelial cells. We report that ozone exposure (0.5 ppm x 1 hr significantly increased DEP-induced IL-8 gene expression in A549 cells (117 ± 19 pg/ml, n = 6, p < 0.05 as compared to cultures treated with DEP (100 μg/ml x 4 hr alone (31 ± 3 pg/ml, n = 6, or cultures exposed to purified air (24 ± 6 pg/ml, n = 6. The increased DEP-induced IL-8 gene expression following ozone exposure was attributed to ozone-induced increase in the activity of the transcription factors NF-κB and NF-IL6. The results of the present study indicate that ozone exposure enhances the toxicity of DEP in human airway epithelial cells by augmenting IL-8 gene expression, a potent chemoattractant of neutrophils in the lung.

  8. Acidic pH stimulates the production of the angiogenic CXC chemokine, CXCL8 (interleukin-8), in human adult mesenchymal stem cells via the extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and NF-kappaB pathways.

    Science.gov (United States)

    Bischoff, David S; Zhu, Jian-Hua; Makhijani, Nalini S; Yamaguchi, Dean T

    2008-07-01

    Blood vessel injury results in limited oxygen tension and diffusion leading to hypoxia, increased anaerobic metabolism, and elevated production of acidic metabolites that cannot be easily removed due to the reduced blood flow. Therefore, an acidic extracellular pH occurs in the local microenvironment of disrupted bone. The potential role of acidic pH and glu-leu-arg (ELR(+)) CXC chemokines in early events in bone repair was studied in human mesenchymal stem cells (hMSCs) treated with medium of decreasing pH (7.4, 7.0, 6.7, and 6.4). The cells showed a reciprocal increase in CXCL8 (interleukin-8, IL-8) mRNA levels as extracellular pH decreased. At pH 6.4, CXCL8 mRNA was induced >60x in comparison to levels at pH 7.4. hMSCs treated with osteogenic medium (OGM) also showed an increase in CXCL8 mRNA with decreasing pH; although, at a lower level than that seen in cells grown in non-OGM. CXCL8 protein was secreted into the medium at all pHs with maximal induction at pH 6.7. Inhibition of the G-protein-coupled receptor alpha, G(alphai), suppressed CXCL8 levels in response to acidic pH; whereas phospholipase C inhibition had no effect on CXCL8. The use of specific mitogen-activated protein kinase (MAPK) signal transduction inhibitors indicated that the pH-dependent increase in CXCL8 mRNA is due to activation of ERK and p38 pathways. The JNK pathway was not involved. NF-kappaB inhibition resulted in a decrease in CXCL8 levels in hMSCs grown in non-OGM. However, OGM-differentiated hMSCs showed an increase in CXCL8 levels when treated with the NF-kappaB inhibitor PDTC, a pyrrolidine derivative of dithiocarbamate. 2008 Wiley-Liss, Inc.

  9. Risk modification of colorectal cancer susceptibility by interleukin-8 -251T>A polymorphism in Malaysians.

    Science.gov (United States)

    Mustapha, Mohd Aminudin; Shahpudin, Siti Nurfatimah Mohd; Aziz, Ahmad Aizat Abdul; Ankathil, Ravindran

    2012-06-07

    To investigate the allele and genotype frequencies and associated risk of interleukin (IL)-8 -251T>A polymorphism on colorectal cancer (CRC) susceptibility risk. Peripheral blood samples of 255 normal controls and 255 clinically and histopathologically confirmed CRC patients were genotyped for IL-8 -251T>A polymorphism employing allele-specific polymerase chain reaction. The relative association of variant allele and genotypes with CRC susceptibility risk was determined by calculating the odds ratios (ORs). Corresponding χ² tests on the CRC patients and controls were carried out and 95% confidence intervals (CIs) were determined using Fisher's exact test. The allele frequencies and its risk association were calculated using FAMHAP, haplotype association analysis software. On comparing the frequencies of genotypes of patients and controls, the homozygous variant AA was significantly higher in CRC patients (P = 0.002) compared to controls. Investigation on the association of the polymorphic genotypes with CRC susceptibility risk, showed that the homozygous variant IL-8 -251AA had a significantly increased risk with OR 3.600 (95% CI: 1.550-8.481, P = 0.001). In the case of allele frequencies, variant allele A of IL-8 -251 showed a significantly increased risk of CRC predisposition with OR 1.32 (95% CI: 1.03-1.69, P = 0.003). Variant allele and genotype of IL-8 (-251T>A) was significantly associated with CRC susceptibility risk and could be considered as a high-risk variant for CRC predisposition.

  10. Serum levels of interleukin-6 and interleukin-8 as diagnostic markers of acute pyelonephritis in children

    Directory of Open Access Journals (Sweden)

    Abolfazl Mahyar

    2013-05-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Early diagnosis and treatment of acute pyelonephritis in children is of special importance in order to prevent serious complications. This study was conducted to determine the diagnostic value of serum interleukin (IL-6 and IL-8 in children with acute pyelonephritis. &lt;b&gt;Methods:&lt;/b&gt; Eighty seven patients between 1 month to 12 years old with urinary tract infection (UTI were divided into 2 groups based on the result of 99m-technetium dimercapto-succinic acid (DMSA renal scan: acute pyelonephritis (n=37 and lower UTI (n=50 groups. White blood cell (WBC count, neutrophil (Neutl count, erythrocyte sedimentation rate (ESR, C-reactive protein (CRP concentration, platelet count, and serum IL-6 and IL-8 concentrations of both groups were measured and compared . &lt;b&gt;Results:&lt;/b&gt; There was a significant difference between two groups regarding WBC count, Neutl count, ESR, and CRP concentration (P&lt;0.05. In addition, the difference between the two groups regarding serum IL-6 and IL-8 concentrations was not significant (IL-6, 60 and 35.4 pg/mL and IL-8, 404 and 617 pg/mL, respectively. The sensitivity and specificity of serum IL-6 and IL-8 for diagnosis of acute pyelonephritis were 73%, 42% and 78%, 32%, respectively. Sensitivity, specificity, negative and positive predictive values of serum IL-6 and IL-8 were less than those of acute phase serum reactants such as CRP. &lt;b&gt;Conclusion:&lt;/b&gt; This study showed that there was no significant difference between acute pyelonephritis and lower UTI groups regarding serum IL-6 and IL-8 levels. Therefore, despite confirming results of previous studies, it seems that IL-6 and IL-8 are not suitable markers for differentiating between acute pyelonephritis and lower UTI.

  11. Renal function influences interleukin-8 background production by cultured human mesothelial cells

    NARCIS (Netherlands)

    Visser, C. E.; Brouwer-Steenbergen, J. J.; Postmus, P. E.; Meijer, S.; Struijk, D. G.; Krediet, R. T.; Beelen, R. H.

    1996-01-01

    Previous studies have demonstrated that mesothelial cells (MC) are important in the local host defense system of the peritoneal cavity. Most studies on the function of MC are performed on MC derived from material of patients with normal renal function (NRF). The aim of the present study was to

  12. Interleukin 8 in progression of hormone-dependent early breast cancer

    Indian Academy of Sciences (India)

    HER2 status was determined on paraffin-embedded tumour tissue sections by CISH. IL8 levels were determined by ELISA in cytosol tumour extracts of 65 patients with long-term follow-up (144 months). Nonparametric statistical tests were used for data analyses. Patients with low IL8 levels(M<88.8 pg/mg) had significantly ...

  13. Thymosin beta-4 promotes mesenchymal stem cell proliferation via an interleukin-8-dependent mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Byung-Joon [Department of Plastic and Reconstructive Surgery, Korea University Medical Center, Gojan 1-dong, Danwon-gu, Ansan-si, Gyeonggi-do 425-707 (Korea, Republic of); Yang, Yoolhee; Kyung Shim, Su [Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Yang, Heung-Mo [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Cho, Daeho, E-mail: cdhkor@sookmyung.ac.kr [Department of Life Science, Sookmyung Women' s University, Hyochangwon-gil 52, Yongsan-gu, Seoul 140-742 (Korea, Republic of); Ik Bang, Sa, E-mail: si55.bang@samsung.com [Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of)

    2013-10-15

    Mesenchymal stem cells (MSCs) hold great promise for the field of tissue regeneration. Because only a limited number of MSCs can be obtained from each donor site, it is important to establish standard methods for MSC expansion using growth and trophic factors. Thymosin β4 (Tβ4) is a novel trophic factor that has antimicrobial effects and the potential to promote tissue repair. Tβ4 is a ubiquitous, naturally-occurring peptide in the wound bed. Therefore, the relationship between Tβ4 and MSCs, especially adjacent adipose tissue-derived stem cells (ASCs), merits consideration. Exogenous Tβ4 treatment enhanced the proliferation of human ASCs, resulting in prominent nuclear localization of PCNA immunoreactivity. In addition, exogenous Tβ4 also increased IL-8 secretion and blocking of IL-8 with neutralizing antibodies decreased Tβ4-induced ASC proliferation, suggesting that IL-8 is a critical mediator of Tβ4-enhanced proliferation. Moreover, Tβ4 activated phosphorylation of ERK1/2 and increased the nuclear translocation of NF-κB. These observation provide that Tβ4 promotes the expansion of human ASCs via an IL-8-dependent mechanism that involves the ERK and NF-κB pathways. Therefore, Tβ4 could be used as a tool for MSC expansion in cell therapeutics. - Highlights: • This is fundamental information required to correlate Tβ4 with MSC expansion. • MSC expansion by Tβ4 is involved in enhancement of IL-8 and ERK/NF-κB pathway. • Tβ4 could be used as a tool for MSC expansion in cell therapeutics.

  14. Urine interleukin-8 is a marker for urinary tract infection in postoperative patients

    NARCIS (Netherlands)

    Olszyna, D. P.; Vermeulen, H.; Baan, A. H.; Speelman, P.; van Deventer, S. J.; Gouma, D. J.; van der Poll, T.

    2001-01-01

    BACKGROUND: Urine of patients with urinary tract infection (UTI) contains high levels of interleukin (IL)-6 and IL-8. However, knowledge of the kinetics of their release in urine is limited. We therefore compared the appearance of IL-6 and IL-8 in urine after uncomplicated surgery and surgery

  15. Interleukin-8 and Its Role During EMT | Center for Cancer Research

    Science.gov (United States)

    The switch of cancer cells from an epithelial to a mesenchymal-like phenotype, designated as epithelial-to-mesenchymal transition or EMT, is known to induce cell motility and invasiveness and appears to be critical for the dissemination of solid tumors and drug resistance. An understanding of the signaling events that induce tumor EMT could lead to novel ways to prevent metastasis.

  16. 25-OH Vitamin D and Interleukin-8: Emerging Biomarkers in Cutaneous Melanoma Development and Progression

    Directory of Open Access Journals (Sweden)

    Corina-Daniela Ene

    2015-01-01

    Full Text Available Background. There are several circulatory biomarkers that are involved in forecasting the clinical outcome of cutaneous melanoma. Serum/plasma vitamin D status is one of the markers intensively studied in this type of cutaneous cancer. The combination of validated serum biomarkers (like LDH with new biomarkers such as IL-8, angiogenic factor, and vitamin D is still at the dawn of research. Hence, we are aiming to establish the predictive power of inflammatory biomarkers, such as IL-8, and metabolic ones, such as vitamin D. These candidate biomarkers are intended to aid classical biomarkers, such as LDH, in the prognosis of cutaneous melanoma. Methods. Serum vitamin D and IL-8 were quantified in melanoma patients and in matching healthy controls. Results. Median serum vitamin D concentrations were significantly lower (p=0.003 in melanoma patients as compared to healthy control subjects, while around 65% of the investigated patients have proven a severe circulatory deficiency of this vitamin. IL-8 was found increased (p=0.001 in melanoma patients as compared to controls. Conclusion. Upregulation of proangiogenic factors associated with vitamin D deficiency can prove to be potent future biomarkers candidates, enhancing the predictive power of classical LDH.

  17. A novel bacterial transport mechanism of Acinetobacter baumannii via activated human neutrophils through interleukin-8.

    Science.gov (United States)

    Kamoshida, Go; Tansho-Nagakawa, Shigeru; Kikuchi-Ueda, Takane; Nakano, Ryuichi; Hikosaka, Kenji; Nishida, Satoshi; Ubagai, Tsuneyuki; Higashi, Shouichi; Ono, Yasuo

    2016-12-01

    Hospital-acquired infections as a result of Acinetobacter baumannii have become problematic because of high rates of drug resistance. Although neutrophils play a critical role in early protection against bacterial infection, their interactions with A. baumannii remain largely unknown. To elucidate the interactions between A. baumannii and human neutrophils, we cocultured these cells and analyzed them by microscopy and flow cytometry. We found that A. baumannii adhered to neutrophils. We next examined neutrophil and A. baumannii infiltration into Matrigel basement membranes by an in vitro transmigration assay. Neutrophils were activated by A. baumannii, and invasion was enhanced. More interestingly, A. baumannii was transported together by infiltrating neutrophils. Furthermore, we observed by live cell imaging that A. baumannii and neutrophils moved together. In addition, A. baumannii-activated neutrophils showed increased IL-8 production. The transport of A. baumannii was suppressed by inhibiting neutrophil infiltration by blocking the effect of IL-8. A. baumannii appears to use neutrophils for transport by activating these cells via IL-8. In this study, we revealed a novel bacterial transport mechanism that A. baumannii exploits human neutrophils by adhering to and inducing IL-8 release for bacterial portage. This mechanism might be a new treatment target. © Society for Leukocyte Biology.

  18. Interleukin 8 in progression of hormone-dependent early breast cancer

    Indian Academy of Sciences (India)

    Many studies have confirmed high levels ofinterleukin 8 (IL8) in HER2-enriched and basal-like (ER–) primary breast tumours, but less is known about thesignificance of IL8 in hormone-dependent breast cancer. The aim of this study was to evaluate the prognostic significance of IL8 and clinicopathological parameters in ...

  19. Interleukin 8 in progression of hormone-dependent early breast cancer

    Indian Academy of Sciences (India)

    2017-04-18

    Apr 18, 2017 ... 1. Background. Breast cancer is hormone-dependent disease with great ge- netical, pathological and clinical heterogeneity. Hormone receptors (ER and PR) together with human epidermal growth factor receptor 2 (HER2) are the main determinants of breast cancer and still the most important established.

  20. Withania somnifera targets interleukin-8 and cyclooxygenase-2 in human prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Anand Setty Balakrishnan

    2017-06-01

    Conclusion: Our results indicate that inherent metastatic and selective inhibitory potential of W. somnifera against PC. W. somnifera may be a good therapeutic agent in addition to the existing drugs for PC. Further studies with more prostate tissue samples are warranted.

  1. Dopamine attenuates the chemoattractant effect of interleukin-8: a novel role in the systemic inflammatory response syndrome.

    LENUS (Irish Health Repository)

    Sookhai, S

    2012-02-03

    Activated neutrophil (PMN) adherence to vascular endothelium comprises a key step for both transendothelial migration and initiation of potentially deleterious release of PMN products. The biogenic amine, dopamine (DA), has been used for several decades in patients to maintain hemodynamic stability. The effect of dopamine on PMN transendothelial migration and adhesion receptor expression and on the endothelial molecules, E-selectin and ICAM-1, was evaluated. PMN were isolated from healthy controls, stimulated with lipopolysaccharide (LPS), and tumor necrosis factor-alpha (TNF-alpha) and treated with dopamine. CD 11b and CD 18 PMN adhesion receptor expression were assessed flow cytometrically. In a separate experiment, the chemoattractant peptide, IL-8, was placed in the lower chamber of transwells, and PMN migration was assessed. Human umbilical vein endothelial cells (HUVEC) were stimulated with LPS\\/TNF-alpha and incubated with dopamine. ICAM-1 and E-selectin endothelial molecule expression were assessed flow cytometrically. There was a significant increase in transendothelial migration in stimulated PMN compared with normal PMN (40 vs. 14%, P < 0.001). In addition, PMN CD11b\\/CD18 was significantly upregulated in stimulated PMN compared with normal PMN (252.4\\/352.4 vs. 76.7\\/139.4, P < 0.001) as were endothelial E-selectin\\/ICAM-1 expression compared with normal EC (8.1\\/9 vs. 3.9\\/3.8, P < 0.05). After treatment with dopamine, PMN transmigration was significantly decreased compared with stimulated PMN (8% vs. 40%, P < 0.001). Furthermore, dopamine also attenuated PMN CD11b\\/CD18 and the endothelial molecules E-selectin and ICAM-1 compared with stimulated PMN\\/EC that were not treated dopamine (174\\/240 vs. 252\\/352, P < 0.05 and 4\\/4.4 vs. 8.1\\/9, P < 0.05. respectively). The chemoattractant effect of IL-8 was also attenuated. These results identify for the first time that dopamine attenuates the initial interaction between PMN and the endothelium, and consequently, modulates PMN exudation. Thus, biogenic amines, including dopamine, may function as anti-inflammatory cytokines.

  2. EGFRvIII promotes glioma angiogenesis and growth through the NF-κB, interleukin-8 pathway.

    Science.gov (United States)

    Bonavia, R; Inda, M M; Vandenberg, S; Cheng, S-Y; Nagane, M; Hadwiger, P; Tan, P; Sah, D W Y; Cavenee, W K; Furnari, F B

    2012-09-06

    Sustaining a high growth rate requires tumors to exploit resources in their microenvironment. One example of this is the extensive angiogenesis that is a typical feature of high-grade gliomas. Here, we show that expression of the constitutively active mutant epidermal growth factor receptor, ΔEGFR (EGFRvIII, EGFR*, de2-7EGFR) is associated with significantly higher expression levels of the pro-angiogenic factor interleukin (IL)-8 in human glioma specimens and glioma stem cells. Furthermore, the ectopic expression of ΔEGFR in different glioma cell lines caused up to 60-fold increases in the secretion of IL-8. Xenografts of these cells exhibit increased neovascularization, which is not elicited by cells overexpressing wild-type (wt)EGFR or ΔEGFR with an additional kinase domain mutation. Analysis of the regulation of IL-8 by site-directed mutagenesis of its promoter showed that ΔEGFR regulates its expression through the transcription factors nuclear factor (NF)-κB, activator protein 1 (AP-1) and CCAAT/enhancer binding protein (C/EBP). Glioma cells overexpressing ΔEGFR showed constitutive activation and DNA binding of NF-κB, overexpression of c-Jun and activation of its upstream kinase c-Jun N-terminal kinase (JNK) and overexpression of C/EBPβ. Selective pharmacological or genetic targeting of the NF-κB or AP-1 pathways efficiently blocked promoter activity and secretion of IL-8. Moreover, RNA interference-mediated knock-down of either IL-8 or the NF-κB subunit p65, in ΔEGFR-expressing cells attenuated their ability to form tumors and to induce angiogenesis when injected subcutaneously into nude mice. On the contrary, the overexpression of IL-8 in glioma cells lacking ΔEGFR potently enhanced their tumorigenicity and produced highly vascularized tumors, suggesting the importance of this cytokine and its transcription regulators in promoting glioma angiogenesis and tumor growth.

  3. Progressive Increase of Matrix Metalloprotease-9 and Interleukin-8 Serum Levels during Carcinogenic Process in Human Colorectal Tract

    Science.gov (United States)

    Biasi, Fiorella; Guina, Tina; Maina, Marco; Nano, Mario; Falcone, Alessandro; Aroasio, Emiliano; Saracco, Giorgio Maria; Papotti, Mauro; Leonarduzzi, Gabriella; Poli, Giuseppe

    2012-01-01

    Background Inflammatory reactions, known to promote tumor growth and invasion, have been found associated with colorectal carcinoma (CRC). Macrophages are the chief component of the inflammatory infiltration that occurs early in the progression from non-invasive to malignant tumor, with a switch from the pro-inflammatory phenotype to the tumor-promoting phenotype. Tumor and stroma are additional sources of inflammation-related molecules. The study aimed to evaluate, during colorectal carcinogenesis from benign to malignant phases: i) the trend of serum levels of IL-8, IL-6, TGFβ1, VEGF and MMPs; ii) the parallel trend of CRP serum levels; iii) derangement of the principal TGFβ1 receptors (TGFβ1RI/RII) in tumor tissues. Methodology/Principal findings 96 patients with colon adenomas or CRC at different stages of progression, and 17 controls, were recruited. Serum IL-8, IL-6, TGFβ1, VEGF, MMPs and CRP levels were analyzed before endoscopy or surgery. TGFβ1 receptors were evaluated in adenoma biopsies and surgically-removed colorectal adenocarcinomas. Serum levels of IL-8 in adenocarcinoma patients were increased from stage II, when also the enzymatic activity of MMP-9 increased. Of note, the increasing trend of the two serum markers was found significantly correlated. Trend of serum CRP was also very similar to that of IL-8 and MMP-9, but just below statistical significance. TGFβ1 levels were lower at stage III CRC, while IL-6 and VEGF levels had no significant variations. In tissue specimens, TGFβ1 receptors were already absent in about 50% of adenomas, and this percentage of missing receptors markedly increased in CRC stages III and IV. Conclusions Combined quantification of serum IL-8, MMP-9 and CRP, appears a reliable and advanced index of inflammation-related processes during malignant phase of colorectal carcinogenesis, since these molecules remain within normal range in colorectal adenoma bearing patients, while consistently increase in the blood of CRC patients, even if from stage II only. PMID:22848630

  4. High concentrations of pepsin in bronchoalveolar lavage fluid from children with cystic fibrosis are associated with high interleukin-8 concentrations.

    LENUS (Irish Health Repository)

    McNally, P

    2011-02-01

    Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated.

  5. Transforming growth factor-β2 and endotoxin interact to regulate homeostasis via interleukin-8 levels in the immature intestine

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh; Sangild, Per Torp; Østergaard, Mette Viberg

    2014-01-01

    plays an important role and hypothesize that transforming growth factor β2 (TGF-β2) acts in synergy with bacterial LPS to control IL-8 levels, thereby supporting intestinal homeostasis. Preterm pigs were fed colostrum (containing TGF-β2) or infant formula with or without antibiotics (COLOS, n = 27; ANTI...

  6. miR-16 targets transcriptional corepressor SMRT and modulates NF-kappaB-regulated transactivation of interleukin-8 gene.

    Directory of Open Access Journals (Sweden)

    Rui Zhou

    Full Text Available The signaling pathways associated with the Toll-like receptors (TLRs and nuclear factor-kappaB (NF-κB are essential to pro-inflammatory cytokine and chemokine expression, as well as initiating innate epithelial immune responses. The TLR/NF-κB signaling pathways must be stringently controlled through an intricate network of positive and negative regulatory elements. MicroRNAs (miRNAs are non-coding small RNAs that regulate the stability and/or translation of protein-coding mRNAs. Herein we report that miR-16 promotes NF-κB-regulated transactivation of the IL-8 gene by suppression of the silencing mediator for retinoid and thyroid hormone receptor (SMRT. LPS stimulation activated miR-16 gene transcription in human monocytes (U937 and biliary epithelial cells (H69 through MAPK-dependent mechanisms. Transfection of cells with the miR-16 precursor promoted LPS-induced production of IL-8, IL-6, and IL-1α, without a significant effect on their RNA stability. Instead, an increase in NF-κB-regulated transactivation of the IL-8 gene was confirmed in cells following transfection of miR-16 precursor. Importantly, miR-16 targeted the 3'-untranslated region of SMRT and caused translational suppression of SMRT. LPS decreased SMRT expression via upregulation of miR-16. Moreover, functional manipulation of SMRT altered NF-κB-regulated transactivation of LPS-induced IL-8 expression. These data suggest that miR-16 targets SMRT and modulates NF-κB-regulated transactivation of the IL-8 gene.

  7. Differential in situ distribution of interleukin-8, monocyte chemoattractant protein-1 and Rantes in human chronic periapical granuloma.

    Science.gov (United States)

    Marton, I J; Rot, A; Schwarzinger, E; Szakáll, S; Radics, T; Vályi-Nagy, I; Kiss, C

    2000-02-01

    In situ distribution of three prototype chemokines interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and Rantes was determined in chronic human periapical granulomas by immunohistochemistry using monoclonal antibodies. IL-8 was found primarily in the cytoplasm of the Malassez epithelial cells. MCP-1 immunoreactivity was confined to the endothelial cells that lined small venules. Each of the three investigated chemokines, including Rantes, exhibited a characteristic binding pattern to the extracellular matrix of the lesion. The observed chemokines may play a role in establishing the cellular composition of chronic apical periodontitis, thus augmenting the intensity of local inflammation and tissue damage.

  8. SNAIL regulates interleukin-8 expression, stem cell-like activity, and tumorigenicity of human colorectal carcinoma cells.

    Science.gov (United States)

    Hwang, Wei-Lun; Yang, Muh-Hwa; Tsai, Ming-Long; Lan, Hsin-Yi; Su, Shu-Han; Chang, Shih-Ching; Teng, Hao-Wei; Yang, Shung-Haur; Lan, Yuan-Tzu; Chiou, Shih-Hwa; Wang, Hsei-Wei

    2011-07-01

    Some cancer cells have activities that are similar to those of stem cells from normal tissues, and cell dedifferentiation correlates with poor prognosis. Little is known about the mechanisms that regulate the stem cell-like features of cancer cells; we investigated genes associated with stem cell-like features of colorectal cancer (CRC) cells. We isolated colonospheres from primary CRC tissues and cell lines and characterized their gene expression patterns by microarray analysis. We also investigated the biological features of the colonosphere cells. Expanded CRC colonospheres contained cells that expressed high levels of CD44 and CD166, which are markers of colon cancer stem cells, and had many features of cancer stem cells, including chemoresistance and radioresistance, the ability to initiate tumor formation, and activation of epithelial-mesenchymal transition (EMT). SNAIL, an activator of EMT, was expressed at high levels by CRC colonospheres. Overexpression of Snail in CRC cells induced most properties of colonospheres, including cell dedifferentiation. Two hundred twenty-seven SNAIL-activated genes were up-regulated in colonospheres; gene regulatory networks centered around interleukin (IL)-8 and JUN. Blocking IL-8 expression or activity disrupted SNAIL-induced stem cell-like features of colonospheres. We observed that SNAIL activated the expression of IL8 by direct binding to its E3/E4 E-boxes. In CRC tissues, SNAIL and IL-8 were coexpressed with the stem cell marker CD44 but not with CD133 or CD24. In human CRC tissues, SNAIL regulates expression of IL-8 and other genes to induce cancer stem cell activities. Strategies that disrupt this pathway might be developed to block tumor formation by cancer stem cells. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Gene expression signature for biliary atresia and a role for Interleukin-8 in pathogenesis of experimental disease

    Science.gov (United States)

    Bessho, Kazuhiko; Mourya, Reena; Shivakumar, Pranavkumar; Walters, Stephanie; Magee, John C; Rao, Marepalli; Jegga, Anil G; Bezerra, Jorge A

    2014-01-01

    Biliary atresia is a progressive fibroinflammatory obstruction of extrahepatic bile ducts that presents as neonatal cholestasis. Due to the overlap in clinical, biochemical, and histological features with other causes of cholestasis, the diagnosis requires an intraoperative cholangiogram. Thus, we determined whether diseased livers express a gene expression signature unique to biliary atresia. Applying stringent statistical analysis to a genome-wide liver expression platform of 64 infants with biliary atresia at the time of diagnosis, 14 age-appropriate subjects with intrahepatic cholestasis as diseased controls, and 7 normal controls, we identified 15 genes uniquely expressed in biliary atresia with an accuracy of 92.3%. Among these genes, IL8 and LAMC2 were sufficient to classify subjects with biliary atresia distinctly from diseased controls with an area under the curve of 0.934 (95%CI: 0.84-1.03), sensitivity of 96.9%, and specificity of 85.7% using their combined first principal component. Direct measurement of IL8 protein in the serum, however, was not different between the two groups. To investigate whether the liver-restricted increase in IL8 was relevant to disease pathogenesis, we inactivated the signaling of IL8 homologs by genetic targeting of the Cxcr2 receptor in a murine model of experimental biliary atresia. Disruption of Cxcr2 shortened the duration of cholestasis, decreased the incidence of bile duct obstruction, and improved survival above wild-type neonatal mice. Conclusion: The hepatic expression of IL8 and LAMC2 has high sensitivity for biliary atresia at diagnosis and may serve as a biomarker of disease, with an important role for the IL8 signaling in experimental biliary atresia. PMID:24493287

  10. Interleukin-17 induces hyperresponsive interleukin-8 and interleukin-6 production to tumor necrosis factor-alpha in structural lung cells

    NARCIS (Netherlands)

    van den Berg, Arjen; Kuiper, Mathys; Snoek, Mieke; Timens, Wim; Postma, Dirkje S.; Jansen, Henk M.; Lutter, René

    2005-01-01

    Lung epithelial cells contribute to local inflammation by the production of pro-inflammatory mediators like interleukin (IL)-8 and IL-6. Although their production depends on gene transcription, previous studies showed that post-transcriptional mechanisms modulate IL-8 and IL-6 production. Human lung

  11. Progressive increase of matrix metalloprotease-9 and interleukin-8 serum levels during carcinogenic process in human colorectal tract.

    Directory of Open Access Journals (Sweden)

    Fiorella Biasi

    Full Text Available BACKGROUND: Inflammatory reactions, known to promote tumor growth and invasion, have been found associated with colorectal carcinoma (CRC. Macrophages are the chief component of the inflammatory infiltration that occurs early in the progression from non-invasive to malignant tumor, with a switch from the pro-inflammatory phenotype to the tumor-promoting phenotype. Tumor and stroma are additional sources of inflammation-related molecules. The study aimed to evaluate, during colorectal carcinogenesis from benign to malignant phases: i the trend of serum levels of IL-8, IL-6, TGFβ1, VEGF and MMPs; ii the parallel trend of CRP serum levels; iii derangement of the principal TGFβ1 receptors (TGFβ1RI/RII in tumor tissues. METHODOLOGY/PRINCIPAL FINDINGS: 96 patients with colon adenomas or CRC at different stages of progression, and 17 controls, were recruited. Serum IL-8, IL-6, TGFβ1, VEGF, MMPs and CRP levels were analyzed before endoscopy or surgery. TGFβ1 receptors were evaluated in adenoma biopsies and surgically-removed colorectal adenocarcinomas. Serum levels of IL-8 in adenocarcinoma patients were increased from stage II, when also the enzymatic activity of MMP-9 increased. Of note, the increasing trend of the two serum markers was found significantly correlated. Trend of serum CRP was also very similar to that of IL-8 and MMP-9, but just below statistical significance. TGFβ1 levels were lower at stage III CRC, while IL-6 and VEGF levels had no significant variations. In tissue specimens, TGFβ1 receptors were already absent in about 50% of adenomas, and this percentage of missing receptors markedly increased in CRC stages III and IV. CONCLUSIONS: Combined quantification of serum IL-8, MMP-9 and CRP, appears a reliable and advanced index of inflammation-related processes during malignant phase of colorectal carcinogenesis, since these molecules remain within normal range in colorectal adenoma bearing patients, while consistently increase in the blood of CRC patients, even if from stage II only.

  12. SRC-mediated EGF Receptor Activation Regulates Ozone-induced Interleukin 8 Expression in Human Bronchial Epithelial Cells

    Science.gov (United States)

    BACKGROUND: Human exposure to ozone (03) results in pulmonary function decrements and airway inflammation. The mechanisms underlying these adverse effects remain unclear. Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of lung inflammation. ...

  13. Pneumocystis carinii major surface glycoprotein induces interleukin-8 and monocyte chemoattractant protein-1 release from a human alveolar epithelial cell line

    DEFF Research Database (Denmark)

    Benfield, T L; Lundgren, Bettina; Shelhamer, J H

    1999-01-01

    (IL-8) and monocyte chemoattractant protein-1 (MCP-1) from an alveolar epithelial cell line (A549). RESULTS: Incubation of A549 cells with MSG in concentrations from 0.4 to 10 microg mL-1 for 24 h caused dose-dependent increases in IL-8 release (3.4-fold above control, P ..., suggesting that MSG stimulates A549 cells in part through carbohydrate moieties. Dexamethasone significantly inhibited MSG-induced IL-8 release in concentrations of 10-6-10-8 mol L-1 compared with control experiments (P

  14. ACTIVATION OF ERK2 BY RESPIRATORY SYNCYTIAL VIRUS IN A549 CELLS IS LINKED TO THE PRODUCTION OF INTERLEUKIN 8. (R826711C001)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  15. The prognostic role of interleukin-8 (IL-8) and matrix metalloproteinases -2 and -9 in lymph node-negative untreated breast cancer patients.

    Science.gov (United States)

    Milovanovic, J; Todorovic-Rakovic, N; Abu Rabi, Z

    2013-01-01

    To investigate the relationships, if any, between interleukin (IL) -8/matrix metalloproteinase (MMP)-2/ MMP-9 and other prognostic variables in lymph node-negative untreated breast cancer patients, and to determine the prognostic value of these potential biomarkers. The study included 135 patients with known clinicopathological parameters. IL-8, MMP-2 and MMP-9 levels were determined by ELISA in primary tumor tissue lysates. There were no significant relationships between IL-8/MMP-2/MMP-9 expression and available clinicopathological parameters (patient age, menopausal status, tumor size and tumor grade). Estrogen receptor (ER)- patients had higher levels of both IL-8 and MMP-9 (p=0.006 and p=0.04, respectively) compared to ER+ patients; there was a significant negative correlation between ER and IL-8 (p=0.02). MMP-9 expression was significantly higher in patients with higher levels of IL-8 (pnegative breast cancer. Node-negative patients with higher levels of IL-8 should be treated with adjuvant, especially IL-8 targeted therapy.

  16. Influence of corticosteroid pulse therapy on the serum levels of soluble interleukin 2 receptor, interleukin 6 and interleukin 8 in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    van den Brink, H. R.; van Wijk, M. J.; Geertzen, R. G.; Bijlsma, J. W.

    1994-01-01

    To investigate the influence of corticosteroid pulse (CP) therapy on soluble interleukin 2 receptor (sIL-2R), interleukin 6 (IL-6) and IL-8 levels in patients with active rheumatoid arthritis (RA). Twenty-five patients with active RA were studied before and after treatment with intravenous CP

  17. 1α,25-Dihydroxyvitamin D(3) inhibits vascular cellular adhesion molecule-1 expression and interleukin-8 production in human coronary arterial endothelial cells.

    Science.gov (United States)

    Kudo, Keiko; Hasegawa, Shunji; Suzuki, Yasuo; Hirano, Reiji; Wakiguchi, Hiroyuki; Kittaka, Setsuaki; Ichiyama, Takashi

    2012-11-01

    Kawasaki disease is an acute febrile vasculitis of childhood that is associated with elevated production of inflammatory cytokines, causing damage to the coronary arteries. The production of proinflammatory cytokines and expression of adhesion molecules in human coronary arterial endothelial cells (HCAECs) is regulated by nuclear transcription factor-κB (NF-κB) activation. We have previously reported that the active form of vitamin D, 1α,25-dihydroxyvitamin D(3) (1α,25-(OH)(2)D(3)), inhibits tumor necrosis factor-α (TNF-α)-induced NF-κB activation. In this study, we examined the anti-inflammatory effects of 1α,25-(OH)(2)D(3) on TNF-α-induced adhesion molecule expression (vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1)) and cytokine production (interleukin-6 (IL-6) and IL-8) in HCAECs. Pretreatment with 1α,25-(OH)(2)D(3) significantly inhibited TNF-α-induced VCAM-1 expression and IL-8 production in HCAECs. Our results suggest that adjunctive 1α,25-(OH)(2)D(3) therapy may modulate the inflammatory response during Kawasaki disease vasculitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. T lymphocyte recruitment by interleukin-8 (IL-8). IL-8-induced degranulation of neutrophils releases potent chemoattractants for human T lymphocytes both in vitro and in vivo.

    Science.gov (United States)

    Taub, D D; Anver, M; Oppenheim, J J; Longo, D L; Murphy, W J

    1996-01-01

    IL-8 has been shown to be a human neutrophil and T cell chemoattractant in vitro. In an effort to assess the in vivo effects of IL-8 on human leukocyte migration, we examined the ability of rhIL-8 to induce human T cell infiltration using a human/mouse model in which SCID mice were administered human peripheral blood lymphocytes intraperitoneally, followed by subcutaneous injections of rhIL-8. rhIL-8 induced predominantly murine neutrophil accumulation by 4 h after administration while recombinant human macrophage inflammatory protein-1beta (rhMIP-1beta) induced both murine monocytes and human T cell infiltration during the same time period as determined by immunohistology. Interestingly, 72 h after chemokine administration, a marked human T cell infiltrate was observed in the IL-8 injection site suggesting that rhIL-8 may be acting indirectly possibly through a murine neutrophil-derived T cell chemoattractant. This hypothesis was confirmed using granulocyte-depleted SCID mice. Moreover, human neutrophils stimulated in vitro with IL-8 were found to release granule-derived factor(s) that induce in vitro T cell and monocyte chemotaxis and chemokinesis. This T cell and monocyte chemotactic activity was detected in extracts of both azurophilic and specific granules. Together, these results demonstrate that neutrophils store and release, upon stimulation with IL-8 or other neutrophil activators, chemoattractants that mediate T cell and monocyte accumulation at sites of inflammation. PMID:8621778

  19. Prognostic significance of interleukin-8 and CD163-positive cell-infiltration in tumor tissues in patients with oral squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Yohei Fujita

    Full Text Available PURPOSE: We investigated whether serum interleukin (IL-8 reflects the tumor microenvironment and has prognostic value in patients with oral squamous cell carcinoma (OSCC. EXPERIMENTAL DESIGN: Fifty OSCC patients who received radical resection of their tumor(s were enrolled. Preoperative sera were measured for IL-8 by ELISA. Expression of IL-8 and the infiltration of immune cells in tumor tissues were analyzed by an immunohistochemical staining of surgical specimens. RESULTS: We found that disease-free survival (DFS was significantly longer in the Stage I/II OSCC patients with low serum IL-8 levels compared to those with high levels (p = 0.001. The tumor expression of IL-8, i.e., IL-8(T and the density of CD163-positive cells in the tumor invasive front, i.e., CD163(IF were correlated with the serum IL-8 level (p = 0.033 and p = 0.038, respectively, and they were associated with poor clinical outcome (p = 0.007 and p = 0.002, respectively, in DFS in all patients. A multivariate analysis revealed that N status, IL-8(T and CD163(IF significantly affected the DFS of the patients. Further analysis suggested that combination of N status with serum IL-8, IL-8(T or CD163(IF may be a new criterion for discriminating between OSCC patients at high and low risk for tumor relapse. Interestingly, the in vitro experiments demonstrated that IL-8 enhanced generation of CD163-positive M2 macrophages from peripheral blood monocytes, and that the cells produced IL-10. CONCLUSIONS: These findings indicate that IL-8 may be involved in poor clinical outcomes via generation of CD163-positive M2 macrophages, and that these factors in addition to N status may have prognostic value in patients with resectable OSCSS.

  20. Evaluation and comparison of interleukin-8 (IL-8 level in gingival crevicular fluid in health and severity of periodontal disease: A clinico-biochemical study

    Directory of Open Access Journals (Sweden)

    Sushma S Lagdive

    2013-01-01

    Full Text Available Background: Cytokines play an important role in the pathology associated with chronic inflammatory diseases. Because of pro-inflammatory and neutrophil chemotactic properties, the cytokines like interleukins (IL may play a significant role in the pathogenesis of periodontitis. The biological effects of IL-8 are relevant in this regard. Aim: This study was done to compare the level of this molecule in gingival crevicular fluid (GCF from patients with adult periodontitis (experimental group and from individuals with clinically healthy gingival (control group. Materials and Methods: GCF was collected from patients with adult periodontitis and clinically healthy gingival for 30 s using a Periopaper strip and the volume of the sample determined. Following elution of the fluid, assays for IL-8 were carried out by enzyme-linked immunosorbent assay (ELISA. The concentration of IL-8 was calculated in the original volume of GCF on each strip. Results: The level of IL-8 in the experimental group was significantly higher than in the control group ( P < 0.01. The clinical parameters were positively correlated to IL-8, suggesting that the GCF IL-8 exhibited dynamic changes upon severity of periodontal disease ( P < 0.05. Conclusion: These data suggest that level of IL-8 is associated with periodontal status. The level of IL-8 in GCF is valuable in detecting the inflammation of periodontal tissue.

  1. Differences in interleukin 8 expression in Helicobacter pylori-infected gastric mucosa tissues from patients in Bhutan and the Dominican Republic.

    Science.gov (United States)

    Nagashima, Hiroyuki; Iwatani, Shun; Cruz, Modesto; Jiménez Abreu, José A; Tronilo, Lourdes; Rodríguez, Eduardo; Disla, Mildre; Terao, Hideo; Uchida, Tomohisa; Mahachai, Varocha; Vilaichone, Ratha-Korn; Tshering, Lotay; Mitsui, Takahiro; Shiota, Seiji; Graham, David Y; Yamaoka, Yoshio

    2015-01-01

    The outcomes of Helicobacter pylori infection vary geographically. H pylori strains, disease presentation, and environments differ markedly in Bhutan and Dominican Republic. The aims were to compare the strains, histology, and expression of interleukin (IL) 8 and IL-10 from gastric mucosa from the 2 countries. H pylori status was assessed by the combination of rapid urease test, culture, and histology. Histology was evaluated using the updated Sydney System, and cytokines in gastric biopsies were measured using real-time polymerase chain reaction (PCR). There were 138 subjects from Bhutan and 155 from Dominican Republic. The prevalence of H pylori infection was 65% and 59%, respectively. The genotype of cagA was predominantly East Asian type in Bhutan versus Western type in Dominican Republic. Gastritis severity was significantly higher in H pylori-infected subjects from Bhutan than those from Dominican Republic. IL-8 expression by H pylori infection was 5.5-fold increased in Bhutan versus 3-fold in Dominican Republic (P < .001); IL-10 expression was similar. IL-8 expression levels among H pylori-infected cases tended to be positively correlated with polymorphonuclear leucocyte and monocyte infiltration scores in both countries. IL-8 expression among those with grade 2 and 3 polymorphonuclear leucocyte and monocyte infiltration was significantly higher in Bhutan than in Dominican Republic. The difference in IL-8 expression in the 2 countries is reflected in the different disease pattern between them. Whether the dominant factor is differences in H pylori virulence, in host-H pylori-environmental interactions, genetic factors or all remains unclear. However, severity of inflammation appears to be a critical factor in disease pathogenesis. We compared IL-8 messenger RNA levels between the high gastric cancer risk country, Bhutan (mainly East Asian-type H pylori), and the lower gastric cancer risk country, Dominican Republic (mainly Western-type H pylori). Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Differences in interleukin-8 expression in Helicobacter pylori-infected gastric mucosa tissues from patients in Bhutan and the Dominican Republic

    Science.gov (United States)

    Nagashima, Hiroyuki; Iwatani, Shun; Cruz, Modesto; Jiménez Abreu, José A.; Tronilo, Lourdes; Rodríguez, Eduardo; Disla, Mildre; Terao, Hideo; Uchida, Tomohisa; Machachai, Varocha; Vilaichone, Ratha-korn; Tshering, Lotay; Mitsui, Takahiro; Shiota, Seiji; Graham, David Y.; Yamaoka, Yoshio

    2014-01-01

    The outcomes of Helicobacter pylori infection vary geographically. H. pylori strains, disease presentation, and environments differ markedly in Bhutan and Dominican Republic. The aims were to compare the strains, histology and expression of interleukin (IL)-8 and IL-10 from gastric mucosa from the two countries. H. pylori status was assessed by the combination of rapid urease test, culture and histology. Histology was evaluated using the updated Sydney System and cytokines in gastric biopsies were measured using real-time PCR. There were 138 subjects from Bhutan and 155 from Dominican Republic. The prevalence of H. pylori infection was 65% and 59%, respectively. The genotype of cagA was predominantly East-Asian type in Bhutan vs. Western type in Dominican Republic. Gastritis severity was significantly higher in H. pylori-infected subjects from Bhutan than those from Dominican Republic. IL-8 expression by H. pylori-infection was 5.5-fold increase in Bhutan vs. 3-fold in Dominican Republic (p <0.001); IL-10 expression was similar. IL-8 expression levels among H. pylori-infected cases tended to be positively correlated with polymorphonuclear leucocyte (PMN) and monocyte infiltration (MNC) scores in both countries. IL-8 expression among those with grade 2 and 3 PMN and MNC was significantly higher in Bhutan than in Dominican Republic. The difference in IL-8 expression in two countries is reflected in the different disease pattern between them. Whether the dominant factor is differences in H. pylori virulence, in host-H. pylori-environmental interactions, genetic factors or all remains unclear. However, severity of inflammation appears to be a critical factor in disease pathogenesis. We compared IL-8 mRNA levels between high gastric cancer risk country; Bhutan (mainly East Asian type H. pylori) and lower gastric cancer risk country; Dominican Republic (mainly Western type H. pylori). PMID:25454482

  3. Endothelial cells are main producers of interleukin 8 through toll-like receptor 2 and 4 signaling during bacterial infection in leukopenic cancer patients

    NARCIS (Netherlands)

    Nijhuis, CSMO; Vellenga, E; Daenen, SMGJ; Kamps, WA; de Bont, ESJM

    Cancer patients who are leukopenic due to chemotherapy are susceptible to bacterial infections. Normally, clinical conditions during bacterial infections are caused by pathogen-associated molecular patterns, which are components that bind to Toll-like receptor (TLR) 2 (TLR-2) and TLR-4 on

  4. Duration of wound fluid secretion from chronic venous leg ulcers is critical for interleukin-1α, interleukin-1β, interleukin-8 levels and fibroblast activation

    DEFF Research Database (Denmark)

    Zillmer, Rikke; Trøstrup, Hannah; Karlsmark, Tonny

    2011-01-01

    Wound fluid collected from chronic wounds may be used as a simple gauge of the processes taking place in the tissue. There is lack of information on the optimal conditions for wound fluid procurement. We have studied possible diurnal variations and duration of wound fluid accumulation using reten...

  5. Interleukin-8 (IL-8) over-production and autocrine cell activation are key factors in monomethylarsonous acid [MMA(III)]-induced malignant transformation of urothelial cells.

    Science.gov (United States)

    Escudero-Lourdes, C; Wu, T; Camarillo, J M; Gandolfi, A J

    2012-01-01

    The association between chronic human exposure to arsenicals and bladder cancer development is well recognized; however, the underlying molecular mechanisms have not been fully determined. We propose that inflammatory responses can play a pathogenic role in arsenic-related bladder carcinogenesis. In previous studies, it was demonstrated that chronic exposure to 50 nM monomethylarsenous acid [MMA(III)] leads to malignant transformation of an immortalized model of urothelial cells (UROtsa), with only 3 mo of exposure necessary to trigger the transformation-related changes. In the three-month window of exposure, the cells over-expressed pro-inflammatory cytokines (IL-1β, IL-6 and IL-8), consistent with the sustained activation of NFKβ and AP1/c-jun, ERK2, and STAT3. IL-8 was over-expressed within hours after exposure to MMA(III), and sustained over-expression was observed during chronic exposure. In this study, we profiled IL-8 expression in UROtsa cells exposed to 50 nM MMA(III) for 1 to 5 mo. IL-8 expression was increased mainly in cells after 3 mo MMA(III) exposure, and its production was also found increased in tumors derived from these cells after heterotransplantation in SCID mice. UROtsa cells do express both receptors, CXCR1 and CXCR2, suggesting that autocrine cell activation could be important in cell transformation. Supporting this observation and consistent with IL-8 over-expression, CXCR1 internalization was significantly increased after three months of exposure to MMA(III). The expression of MMP-9, cyclin D1, bcl-2, and VGEF was significantly increased in cells exposed to MMA(III) for 3 mo, but these mitogen-activated kinases were significantly decreased after IL-8 gene silencing, together with a decrease in cell proliferation rate and in anchorage-independent colony formation. These results suggest a relevant role of IL-8 in MMA(III)-induced UROtsa cell transformation. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Duration of wound fluid secretion from chronic venous leg ulcers is critical for interleukin-1α, interleukin-1β, interleukin-8 levels and fibroblast activation

    DEFF Research Database (Denmark)

    Zillmer, Rikke; Trøstrup, Hannah; Karlsmark, Tonny

    2011-01-01

    Wound fluid collected from chronic wounds may be used as a simple gauge of the processes taking place in the tissue. There is lack of information on the optimal conditions for wound fluid procurement. We have studied possible diurnal variations and duration of wound fluid accumulation using...... retentive hydrophobic foam on the levels of prototypic cytokines [interleukin (IL)-1α, IL-1β], a chemokine (IL-8) and proteinases [matrix metalloproteinase (MMP)-9] in 23 chronic venous leg ulcer patients. Bioactivity of 1 and 24 h wound fluids, and serum was also compared. There were no significant...

  7. Tumor necrosis factor-alpha but not interleukin-1 beta or interleukin-8 concentrations correlate with angiogenic activity of peritoneal fluid from patients with minimal to mild endometriosis

    NARCIS (Netherlands)

    Maas, J. W.; Calhaz-Jorge, C.; ter Riet, G.; Dunselman, G. A.; de Goeij, A. F.; Struijker-Boudier, H. A.

    2001-01-01

    OBJECTIVE: To assess the angiogenic activity of peritoneal fluid in women with minimal to mild endometriosis and to investigate the relationship between this activity and the concentration of macrophage-derived angiogenic factors and clinical variables, such as phase of menstrual cycle, type of

  8. A Study of Elevated Interleukin-8 (CXCL8 Detection of Leukocyte Migration Inhibitory Activity in Patients Allergic to Beta-Lactam Antibiotics

    Directory of Open Access Journals (Sweden)

    Manabu Abe

    2011-01-01

    Conclusions: Increased CXCL8 levels produced by beta-lactams administration were accompanied by LMIA. CXCL8 may be involved in LMIA and play a role in beta-lactam allergies. In contrast, the LMIA detected in patients with allergies to APAs may be a cytokine or chemokine other than CXCL8.

  9. The diagnostic utility of procalcitonin, interleukin-6 and interleukin-8, and hyaluronic acid in the Norwegian consensus definition for early-onset neonatal sepsis (EONS

    Directory of Open Access Journals (Sweden)

    Nakstad B

    2018-03-01

    Full Text Available Britt Nakstad1,2 1Department of Paediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway; 2Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway Introduction: A key challenge in identifying serious bacterial infection in new born infants is the nonspecific clinical presentation of early-onset neonatal sepsis (EONS. Routinely used C-reactive protein, white blood cell count, and platelets are nonspecific. We assessed the diagnostic utility of single biomarkers or combinations of procalcitonin (PCT, interleukin (IL-6, IL-8, and hyaluronic acid (HA in newborn infant with EONS, and in human umbilical cord blood (HUCB from deliveries with chorioamnionitis. Materials and methods: Blood was collected from term infants with strictly defined EONS (group 1, n=15, healthy term infants (group 2, n=15, and the umbilical vein from pregnancies with suspected chorioamnionitis (group 3, n=8, and from healthy pregnancies with no signs of infection (group 4, n=15. Results: Neonatal plasma PCT and IL-8 showed good predictive value (90% and 83% for EONS, and the combination of IL-6 or HA with PCT increased the predictability to 87% and 90%, respectively. PCT, IL-6, IL-8, and HA were 8.4-, 4.5-, 3.6-, and 1.9-fold higher when compared with plasma levels in noninfected neonates. PCT, IL-6, and IL-8 in HUCB predicted chorioamnionitis and fever in the delivering mother (89%, 83%, and 72%, respectively. HA was a poor predictor (59%, but its predictability increased in combination with PCT, IL-8, or IL-6. In HUCB from chorioamnionitic deliveries, IL-6, IL-8, and PCT were 23-, 14-, and 2.4-fold higher, respectively, when compared with HUCB from healthy deliveries. There was no correlation between C-reactive protein, white blood cell, and platelet count with PCT, IL-6, IL-8, or HA. Conclusion: In neonates that fulfilled the Norwegian consensus definition of neonatal sepsis, PCT, IL-6, and IL-8, but not HA, have the potential to improve our management of neonates at risk. Except for PCT and IL-8, both with a predictability of >80% in neonatal plasma, combinations of biomarkers increased the predictability for EONS and chorioamnionitis. Keywords: sepsis, newborn, procalcitonin, interleukin, hyaluronic acid

  10. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8.

    LENUS (Irish Health Repository)

    Shanab, Ahmed Abu

    2011-05-01

    Experimental and clinical studies suggest an association between small intestinal bacterial overgrowth (SIBO) and nonalcoholic steatohepatitis (NASH). Liver injury and fibrosis could be related to exposure to bacterial products of intestinal origin and, most notably, endotoxin, including lipopolysaccharide (LPS).

  11. Alternaria Fungus Induces the Production of GM-CSF, Interleukin-6 and Interleukin-8 and Calcium Signaling in Human Airway Epithelium through Protease-Activated Receptor 2

    Science.gov (United States)

    Matsuwaki, Yoshinori; Wada, Kota; White, Thomas; Moriyama, Hiroshi; Kita, Hirohito

    2012-01-01

    Rationale Recent studies suggest that host immune responses to environmental fungi may play an important role in the development of allergic diseases, such as human asthma. Epithelium is considered an active participant in allergic inflammation. We previously reported that aspartate protease from Alternaria induces the activation and degranulation of human eosinophils that are mediated through protease-activated receptor 2 (PAR-2). However, our current knowledge on the innate immune responses of epithelium to environmental fungi is very limited. We investigated the responses of epithelium to fungi and the mechanisms of these responses. Methods Human airway epithelial cell line BEAS-2B and Calu-3 (both from American Type Culture Collection) were incubated with PAR-2 peptides and extracts of various fungi. The cellular responses, including GM-CSF, interleukin (IL)-6, IL-8, eotaxin, eotaxin-2 and RANTES production as well as increases in intracellular calcium concentration ([Ca2+]i), were examined. To characterize the proteases involved in these responses, protease inhibitors such as pepstatin A and alkalo-thermophilic Bacillus inhibitor (ATBI), HIV protease inhibitors and 4-amidinophenylmethanesulfonyl fluoride hydrochloride were used. To investigate the role of PAR-2, PAR-2-agonistic and PAR-2-antagonistic peptides were used. Results PAR-2-activating peptide, but not the control peptide, induced GM-CSF, IL-6 and IL-8 production; these cellular responses were accompanied by a quick and marked increase in [Ca2+]i. Among 7 common environmental fungi, only Alternaria induced GM-CSF, IL-6 and IL-8 production and increased [Ca2+]i response. Both cytokine production and increased [Ca2+]i were significantly inhibited by PAR-2 antagonist peptide and by aspartate protease inhibitors (pepstatin A, ritonavir, nelfinavir and ATBI), but not by the PAR-2 control peptide or by other protease inhibitors. Conclusions Aspartate proteases from Alternaria induce cytokine production and calcium response in airway epithelium that is mediated through PAR-2. This protease-mediated activation of airway epithelium may be implicated in the development and exacerbation of airway allergic disease. PMID:22627362

  12. Effect of stress doses of hydrocortisone on S-100B vs. interleukin-8 and polymorphonuclear elastase levels in human septic shock.

    Science.gov (United States)

    Mussack, Thomas; Briegel, Josef; Schelling, Gustav; Biberthaler, Peter; Jochum, Marianne

    2005-01-01

    Stress doses of hydrocortisone are known to have immunomodulatory effects in patients with hyperdynamic septic shock. The prognosis correlates with the presence and severity of septic encephalopathy. However, neurological evaluation is influenced by the use of analgesia sedation during artificial ventilation. The objective of this study was to demonstrate the effect of stress doses of hydrocortisone during the initial phase of human septic shock on the serum values of the neurospecific protein S-100B in comparison to the inflammation markers interleukin (IL)-8 in serum and polymorphonuclear (PMN) elastase in plasma. A total of 24 consecutive patients, who met the American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock, were enrolled in this prospective, randomized, double-blind, single-center trial. The severity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems. Multi-organ dysfunction syndrome was described by the Sepsis-related Organ Failure Assessment (SOFA) score. All patients were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started in 12 patients with a loading dose of 100 mg and followed by a continuous infusion of 0.18 mg/kg/h for 6 days. Median S-100B serum levels of the hydrocortisone group decreased from 0.32 ng/mL at study entry to 0.07 ng/mL 6 days later without significant differences compared to the placebo group. Initial IL-8 serum levels were significantly higher in the hydrocortisone group up to 12 h after study entry, and significantly decreased from 715 to 17 pg/mL at the end of the observation period. Median PMN elastase plasma levels were not affected by hydrocortisone infusion. Patients with initial S-100B serum levels > 0.50 ng/mL revealed significantly higher SOFA scores up to 30 h, IL-8 serum levels up to 12 h, and PMN elastase plasma levels up to 36 h after study entry than those patients with < or = 0.50 ng/mL. These effects were independent of the amount of fluid correction for hemodilution. Starting S-100B, IL-8 and PMN elastase values of the hydrocortisone group were within the ranges already known in patients with out-of-hospital cardiac arrest or severe traumatic brain injury. Stress doses of hydrocortisone resulted in a significant reduction in IL-8 serum, but not in S-100B serum and PMN elastase plasma concentrations in patients with hyperdynamic septic shock. For the first time, a similar extent of S-100B increase in serum of septic patients at the time of diagnosis was shown as reported for cardiac arrest or severe traumatic brain injury.

  13. Serum levels of tumor necrosis factor-α, interleukin-6 and interleukin-8 are not increased in dyspeptic patients with Helicobacter pylori-associated gastritis

    Directory of Open Access Journals (Sweden)

    Taner Bayraktaroğlu

    2004-01-01

    Full Text Available Introduction: Helicobacter pylori (H. pylori is a non-invasive microorganism causing intense gastric mucosal inflammatory and immune reaction. H. pylori-induced gastric mucosal cytokine overproduction has been clearly documented previously. The stomach has a large surface area and continuous spill-over of locally produced cytokines into the blood stream is a possibility. There are few and conflicting data on circulatory proinflammatory cytokine levels in patients with H. pylori infection.

  14. Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk

    Directory of Open Access Journals (Sweden)

    Kontny Udo

    2008-03-01

    Full Text Available Abstract Background Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia. Methods A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics. Results The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90% and specificity (85%. Conclusion These findings may have clinical implications for risk-based antimicrobial treatment strategies.

  15. Effect of the use of snuff on the levels of interleukin-1 β and interleukin-8 in the gingival crevicular fluid of periodontitis patients.

    Science.gov (United States)

    Pandey, Vijayendra; Salam, Sharib Abdus; Moda, Aman; Agarwal, Preeti; Nath, Sonia; Pulikkotil, Shaju Jacob

    2015-01-01

    Use of smokeless tobacco in the form of moist snuff placed in the oral cavity is popular in rural India. The aim of the present cross-sectional study was to determine the effect of snuff on periodontitis by assessing interleukin (IL)-1 β and IL-8 levels in gingival crevicular fluid. A total of 60 subjects were selected for this study. 40 subjects presented with periodontitis, which included 20 snuff users (SP) and 20 nonsnuff users (NS). 20 periodontally healthy patients formed the controls (healthy control: HC). The clinical parameters recorded were gingival index (GI), plaque index, calculus index, bleeding on probing (BOP), probing depth (PD), recession (RC), and clinical attachment level (CAL). The IL-1 β and IL-8 levels were assessed through enzyme-linked immunosorbent assay (Quantikine(®)). Analysis of variance (ANOVA), post-hoc Tukey's, Kruskal-Walli's ANOVA and Mann-Whitney test was used for comparison among groups and P > 0.05 was considered statistically significant. No significant difference was seen in levels of IL-1 β and IL-8 between SP and NS groups (P = 0.16, 0.97). However, both the periodontitis groups (SP and NS) had increased IL-β levels when compared to HC group (P = 0.01, 0.001). The snuff users showed significant increase in GI, BOP, RC, and CAL when compared with NS (P = 0.002, 0.001, 0.012, 0.002) whereas NS group had significant increase in PD (P = 0.003). Within the limitations of this study, use of snuff does not affect the host inflammatory response associated with periodontitis and leads to RC and increased CAL due to local irritant effect.

  16. Clinical significance of changes of serum gastrin (gas) transforming growth factor-alpha (TGF-α) and interleukin-8 (IL-8) levels after treatment in patients with peptic ulcer

    International Nuclear Information System (INIS)

    Zhou Yuyang

    2007-01-01

    Objective: To explore the clinical significance of changes of serum Gas, TGF-α and IL-8 levels in patients with peptic ulcer. Methods: Serum Gas, TGF-α (with RIA), IL-8 (with ELISA) levels were determined in 56 patients with peptic ulcer both before and after treatment as well as in 35 controls. Results: Before treatment the serum Gas and IL-8 levels were significantly higher than those in controls (P 0.05). Conclusion: Serum Gas, TGF-α and IL-8 levels were closely related to the diseases process of peptic ulcer and were of prognostic values. (authors)

  17. Pulmonary Proteases in the Cystic Fibrosis Lung Induce Interleukin 8 Expression from Bronchial Epithelial Cells via a Heme/Meprin/Epidermal Growth Factor Receptor/Toll-like Receptor Pathway.

    LENUS (Irish Health Repository)

    Cosgrove, Sonya

    2011-03-04

    A high intrapulmonary protease burden is characteristic of cystic fibrosis (CF), and the resulting dysregulation of the protease\\/anti-protease balance has serious implications for inflammation in the CF lung. Because of this inflammation, micro-bleeds can occur releasing hemoglobin into the lung. The aim of this study was to investigate the effect of the protease-rich environment of the CF lung on human hemoglobin and to assess the proinflammatory effect of heme on CF bronchial epithelium. Here, we show that the Pseudomonas proteases (Pseudomonas elastase and alkaline protease) and the neutrophil proteases (neutrophil elastase (NE) and proteinase-3) are capable of almost complete degradation of hemoglobin in vitro but that NE is the predominant protease that cleaves hemoglobin in vivo in CF bronchoalveolar lavage fluid. One of the effects of this is the release of heme, and in this study we show that heme stimulates IL-8 and IL-10 protein production from ΔF508 CFBE41o(-) bronchial epithelial cells. In addition, heme-induced IL-8 expression utilizes a novel pathway involving meprin, EGF receptor, and MyD88. Meprin levels are elevated in CF cell lines and bronchial brushings, thus adding to the proinflammatory milieu. Interestingly, α(1)-antitrypsin, in addition to its ability to neutralize NE and protease-3, can also bind heme and neutralize heme-induced IL-8 from CFBE41o(-) cells. This study illustrates the proinflammatory effects of micro-bleeds in the CF lung, the process by which this occurs, and a potential therapeutic intervention.

  18. Pulmonary proteases in the cystic fibrosis lung induce interleukin 8 expression from bronchial epithelial cells via a heme/meprin/epidermal growth factor receptor/Toll-like receptor pathway.

    LENUS (Irish Health Repository)

    Cosgrove, Sonya

    2012-02-01

    A high intrapulmonary protease burden is characteristic of cystic fibrosis (CF), and the resulting dysregulation of the protease\\/anti-protease balance has serious implications for inflammation in the CF lung. Because of this inflammation, micro-bleeds can occur releasing hemoglobin into the lung. The aim of this study was to investigate the effect of the protease-rich environment of the CF lung on human hemoglobin and to assess the proinflammatory effect of heme on CF bronchial epithelium. Here, we show that the Pseudomonas proteases (Pseudomonas elastase and alkaline protease) and the neutrophil proteases (neutrophil elastase (NE) and proteinase-3) are capable of almost complete degradation of hemoglobin in vitro but that NE is the predominant protease that cleaves hemoglobin in vivo in CF bronchoalveolar lavage fluid. One of the effects of this is the release of heme, and in this study we show that heme stimulates IL-8 and IL-10 protein production from DeltaF508 CFBE41o(-) bronchial epithelial cells. In addition, heme-induced IL-8 expression utilizes a novel pathway involving meprin, EGF receptor, and MyD88. Meprin levels are elevated in CF cell lines and bronchial brushings, thus adding to the proinflammatory milieu. Interestingly, alpha(1)-antitrypsin, in addition to its ability to neutralize NE and protease-3, can also bind heme and neutralize heme-induced IL-8 from CFBE41o(-) cells. This study illustrates the proinflammatory effects of micro-bleeds in the CF lung, the process by which this occurs, and a potential therapeutic intervention.

  19. Effect of Photobiomodulation on Transforming Growth Factor-β1, Platelet-Derived Growth Factor-BB, and Interleukin-8 Release in Palatal Wounds After Free Gingival Graft Harvesting: A Randomized Clinical Study.

    Science.gov (United States)

    Keskiner, Ilker; Lutfioğlu, Muge; Aydogdu, Ahmet; Saygun, N Isil; Serdar, Muhittin A

    2016-06-01

    This study evaluated the impact of photobiomodulation (PBM) on the healing of the donor palatal area following free gingival graft (FGG) harvesting by examining changes in transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF)-BB, and interleukin (IL)-8 levels in palatal wound fluid (PWF). Thirty patients were selected and randomly assigned to receive PBM (laser group) or PBM sham (sham group) in the palatine area after FGG harvesting. A neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (1064 nm) was applied to the test sites immediately after surgery and every 24 h thereafter for 4 days. PWF was collected on Days 7 and 12, and PWF TGF-β1, PDGF-BB, and IL-8 levels were analyzed by enzyme-linked immunosorbent assays (ELISA). PWF TGF-β1, PDGF-BB, and IL-8 levels were significantly lower on Day 12 than on Day 7 for both groups. PWF TGF-β1, PDGF-BB, and IL-8 levels of the laser group were significantly higher than those of sham group on Day 7 (p BB and IL-8 levels between groups on Day 12 were statistically nonsignificant. Observed increases in PWF TGF-β1, PDGF-BB, and IL-8 levels suggest that PBM may accelerate wound healing by stimulating production of selected mediators.

  20. Ketamine inhibits transcription factors activator protein 1 and nuclear factor-kappaB, interleukin-8 production, as well as CD11b and CD16 expression: studies in human leukocytes and leukocytic cell lines.

    NARCIS (Netherlands)

    Welters, I.D.; Hafer, G.; Menzebach, A.; Muhling, J.; Neuhauser, C.; Browning, P.; Goumon, Y.

    2010-01-01

    BACKGROUND: Recent data indicate that ketamine exerts antiinflammatory actions. However, little is known about the signaling mechanisms involved in ketamine-induced immune modulation. In this study, we investigated the effects of ketamine on lipopolysaccharide-induced activation of transcription

  1. Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8 -251 polymorphisms in the risk for the development of distal gastric cancer

    Directory of Open Access Journals (Sweden)

    Maldonado-Garza Hector J

    2007-04-01

    Full Text Available Abstract Background The intensity of the inflammation induced by Helicobacter pylori colonization is associated with the development of distal gastric cancer (GC. The host response to H. pylori has been related to genetic polymorphisms that influence both innate and adaptive immune responses. Our aim was to investigate whether the presence of the TLR4 Asp299Gly, TLR4 Thr399Ile and IL-8-251 A/T polymorphisms had any influence in the development of distal GC in a Mexican population. Methods We studied 337 patients that were divided in two groups: 78 patients with histologically confirmed distal GC and 259 non-cancer controls. The presence of H. pylori in the control population was defined by positive results of at least two of four diagnostic tests: serology, histology, rapid urease test and culture. Human DNA was purified and genotyped for TLR4 Asp299Gly polymorphism by pyrosequencing, for TLR4 Thr399Ile by PCR-RFLP and for IL8-251 by the amplification refractory mutation system (ARMS-PCR. Results The non-cancer control group was found to be in Hardy-Weinberg equilibrium at the polymorphic loci studied (chi-square H-W = 0.58 for IL8-251, 0.42 for TLR4 Asp299Gly and 0.17 for TLR4 Thr399Ile. The frequencies of mutated alleles (homozygous plus heterozygous were compared between cases and controls. We found no significant difference for TLR4- Asp299Gly [the 7.7% of distal GC patients and 7.7 % non-cancer controls (p = 0.82] and for TLR4 Thr399Ile [the 1.3% of GC patients and the 5% of the control population (p = 0.2]. In contrast, for IL-8-251 A/T, 80.77% of the GC patients and 66.4% in the control group age and gender matched had at least one copy of mutated allele (OR = 2.12, 95% CI = 1.1–4.2 (p = 0.023. Conclusion This study showed that the IL8-251*A allele could be related to the development of distal gastric cancer in this Mexican population.

  2. Elevated mRNA expression of PGF2alpha receptor splice variant 2(FP-V2) in human decidua is associated with incomplete mifepristone-misoprostol-induced early medical abortion by regulation of interleukin-8.

    NARCIS (Netherlands)

    Ma, C.; Feng, W.; Han, W.; Lu, Y.; Liu, W.; Sui, Y.; Zhao, N.; Lye, S.J.; Li, J.

    2016-01-01

    OBJECTIVE: The combination of mifepristone and misoprostol is an established method for the induction of early abortion, but 15% of women still experience the unpleasant side effect of incomplete medical abortion. The purpose of this study was to determine whether prostaglandin (PG) F2alpha receptor

  3. High concentrations of circulating interleukin-6 and monocyte chemotactic protein-1 with low concentrations of interleukin-8 were associated with severe chikungunya fever during the 2009-2010 outbreak in Thailand.

    Science.gov (United States)

    Lohachanakul, Jindarat; Phuklia, Weerawat; Thannagith, Montri; Thonsakulprasert, Tipparat; Ubol, Sukathida

    2012-02-01

    The recent outbreak of Chikungunya virus in Thailand caused a rheumatic fever associated with considerable morbidity and fatalities. Thus, it is important to identify biomarker(s) of severe disease induced by this threatening arbovirus. Putative biomarkers in cases of chikungunya fever during an outbreak in the southern part of Thailand in 2009-2010 were identified. Sixty-two patients who had developed fever and myalgia, with or without arthralgia/arthritis, were enrolled and grouped into severe chikungunya fever (CHIKF) (n= 15), mild CHIKF (n= 20) and non-CHIKF (n= 27) to investigate circulating immunological mediators that might serve as markers of severity. Blood samples were taken at presentation (day 1) and 30 days later (day 30) and plasma concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-17, tumor necrosis factor-alpha, monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-1, tissue inhibitor of matrix metalloproteinase-1 and viral load were measured by ELISA. On day 1, severe CHIKF and mild CHIKF groups had viral loads of 10(8.5) and 10(8.3) of RNA copies/mL, respectively. At presentation, all CHIKF patients had circulating concentrations of IL-6 and MCP-1 higher than did non-CHIKF patients, whereas amongst the CHKF patients, the severe CHIKF patients had higher IL-6 concentrations than did mild CHIKF patients. Interestingly, severe CHIKF patients had significantly lower concentrations of circulating IL-8 than the other groups of patients, suggesting that high concentrations of IL-6 and MCP-1 with low concentrations of IL-8 may be a determinant of severe chikungunya virus infection. © 2012 The Societies and Blackwell Publishing Asia Pty Ltd.

  4. NCBI nr-aa BLAST: CBRC-ACAR-01-0732 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ACAR-01-0732 sp|P21109|CXCR1_RABIT High affinity interleukin-8 receptor A (IL-...8R A) (CXCR-1) (CD181 antigen) gb|AAA31375.1| interleukin 8 receptor gb|AAA31376.1| interleukin 8 receptor P21109 1e-113 64% ...

  5. NCBI nr-aa BLAST: CBRC-TBEL-01-0817 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TBEL-01-0817 sp|P21109|CXCR1_RABIT High affinity interleukin-8 receptor A (IL-...8R A) (CXCR-1) (CD181 antigen) gb|AAA31375.1| interleukin 8 receptor gb|AAA31376.1| interleukin 8 receptor P21109 1e-134 68% ...

  6. NCBI nr-aa BLAST: CBRC-EEUR-01-0272 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-EEUR-01-0272 sp|P21109|CXCR1_RABIT High affinity interleukin-8 receptor A (IL-...8R A) (CXCR-1) (CD181 antigen) gb|AAA31375.1| interleukin 8 receptor gb|AAA31376.1| interleukin 8 receptor P21109 1e-141 72% ...

  7. NCBI nr-aa BLAST: CBRC-CPOR-01-0033 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CPOR-01-0033 sp|P21109|CXCR1_RABIT High affinity interleukin-8 receptor A (IL-...8R A) (CXCR-1) (CD181 antigen) gb|AAA31375.1| interleukin 8 receptor gb|AAA31376.1| interleukin 8 receptor P21109 9e-64 80% ...

  8. NCBI nr-aa BLAST: CBRC-OANA-01-0052 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OANA-01-0052 sp|P21109|CXCR1_RABIT High affinity interleukin-8 receptor A (IL-...8R A) (CXCR-1) (CD181 antigen) gb|AAA31375.1| interleukin 8 receptor gb|AAA31376.1| interleukin 8 receptor P21109 1e-114 63% ...

  9. NCBI nr-aa BLAST: CBRC-OCUN-01-0050 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OCUN-01-0050 sp|P21109|CXCR1_RABIT High affinity interleukin-8 receptor A (IL-...8R A) (CXCR-1) (CD181 antigen) gb|AAA31375.1| interleukin 8 receptor gb|AAA31376.1| interleukin 8 receptor P21109 1e-164 81% ...

  10. NCBI nr-aa BLAST: CBRC-CFAM-37-0005 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CFAM-37-0005 sp|P21109|CXCR1_RABIT High affinity interleukin-8 receptor A (IL-...8R A) (CXCR-1) (CD181 antigen) gb|AAA31375.1| interleukin 8 receptor gb|AAA31376.1| interleukin 8 receptor P21109 1e-152 76% ...

  11. NCBI nr-aa BLAST: CBRC-OANA-01-1436 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OANA-01-1436 sp|P21109|CXCR1_RABIT High affinity interleukin-8 receptor A (IL-...8R A) (CXCR-1) (CD181 antigen) gb|AAA31375.1| interleukin 8 receptor gb|AAA31376.1| interleukin 8 receptor P21109 1e-115 59% ...

  12. NCBI nr-aa BLAST: CBRC-RNOR-09-0076 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-RNOR-09-0076 sp|P21109|CXCR1_RABIT High affinity interleukin-8 receptor A (IL-...8R A) (CXCR-1) (CD181 antigen) gb|AAA31375.1| interleukin 8 receptor gb|AAA31376.1| interleukin 8 receptor P21109 1e-127 69% ...

  13. NCBI nr-aa BLAST: CBRC-MMUS-01-0026 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUS-01-0026 sp|P21109|CXCR1_RABIT High affinity interleukin-8 receptor A (IL-...8R A) (CXCR-1) (CD181 antigen) gb|AAA31375.1| interleukin 8 receptor gb|AAA31376.1| interleukin 8 receptor P21109 1e-127 70% ...

  14. NCBI nr-aa BLAST: CBRC-BTAU-01-2915 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-BTAU-01-2915 sp|P21109|CXCR1_RABIT High affinity interleukin-8 receptor A (IL-...8R A) (CXCR-1) (CD181 antigen) gb|AAA31375.1| interleukin 8 receptor gb|AAA31376.1| interleukin 8 receptor P21109 1e-137 72% ...

  15. NCBI nr-aa BLAST: CBRC-TBEL-01-0817 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TBEL-01-0817 ref|NP_000625.1| interleukin 8 receptor alpha [Homo sapiens] sp|P...25024|CXCR1_HUMAN High affinity interleukin-8 receptor A (IL-8R A) (IL-8 receptor type 1) (CXCR-1) (CD181 an...tigen) (CDw128a) emb|CAA46688.1| High affinity interleukin-8 receptor [Homo sapiens] gb|AAA64378.1| interleukin...-8 receptor type A gb|AAB59436.1| interleukin 8 receptor alpha gb|AAA59160.1| interleukin... 8 receptor alpha gb|AAT46689.1| interleukin 8 receptor, alpha [Homo sapiens] emb|CAG46791.1| IL8

  16. NCBI nr-aa BLAST: CBRC-OCUN-01-0050 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OCUN-01-0050 ref|NP_000625.1| interleukin 8 receptor alpha [Homo sapiens] sp|P...25024|CXCR1_HUMAN High affinity interleukin-8 receptor A (IL-8R A) (IL-8 receptor type 1) (CXCR-1) (CD181 an...tigen) (CDw128a) emb|CAA46688.1| High affinity interleukin-8 receptor [Homo sapiens] gb|AAA64378.1| interleukin...-8 receptor type A gb|AAB59436.1| interleukin 8 receptor alpha gb|AAA59160.1| interleukin... 8 receptor alpha gb|AAT46689.1| interleukin 8 receptor, alpha [Homo sapiens] emb|CAG46791.1| IL8

  17. Effects of Standard and/or Glutamine Dipeptide and/or Omega-3 ...

    African Journals Online (AJOL)

    Supplemented Parenteral Nutrition on Neutrophil Functions, Interleukin-8 Level and Length of ... Standard TPN and glutamine and lipid emulsion with omega 3 fatty acids were given to colorectal cancer patients and the effects of these to neutrophil ...

  18. The role of cytokines in cervical ripening: correlations between the concentrations of cytokines and hyaluronic acid in cervical mucus and the induction of hyaluronic acid production by inflammatory cytokines by human cervical fibroblasts.

    Science.gov (United States)

    Ogawa, M; Hirano, H; Tsubaki, H; Kodama, H; Tanaka, T

    1998-07-01

    The purpose of our study was (1) to explain the relationship between levels of inflammatory cytokines and levels of hyaluronic acid in cervical mucus of pregnant women and (2) to investigate whether cytokines promote hyaluronic acid production by human cervical fibroblasts in vitro. The concentration of hyaluronic acid, interleukin-1beta, and interleukin-8 were measured in cervical mucus of pregnant women, and hyaluronic acid production by cytokine-treated (interleukin-1beta and interleukin-8) cultured fibroblasts was measured. Hyaluronic acid concentrations in the mucus of pregnant women with threatened premature labor were higher than in mucus of normal pregnant women (P hyaluronic acid concentrations and interleukin-1beta (P = .018) and interleukin-8 (P = .003) concentrations in cervical mucus. Cytokines (especially interleukin-8) stimulated hyaluronic acid production by cultured cervical fibroblasts. Cytokines induce hyaluronic acid production by human cervical fibroblasts, which may promote cervical ripening.

  19. Adenosine derived from Staphylococcus aureus-engulfed macrophages functions as a potent stimulant for the induction of inflammatory cytokines in mast cells

    DEFF Research Database (Denmark)

    Ma, Ying Jie; Kim, Chan-Hee; Ryu, Kyoung-Hwa

    2011-01-01

    In this study, we attempted to isolate novel mast cell-stimulating molecules from Staphylococcus aureus. Water-soluble extract of S. aureus cell lysate strongly induced human interleukin- 8 in human mast cell line-1 and mouse interleukin-6 in mouse bone marrow-derived mast cells. The active...... adenosine receptor blocker, verified that purified adenosine can induce interleukin-8 production via adenosine receptors on mast cells. Moreover, adenosine was purified from S. aureusengulfed RAW264.7 cells, a murine macrophage cell line, used to induce phagocytosis of S. aureus. These results show a novel...

  20. Building-related symptoms and inflammatory potency of dust from office buildings

    DEFF Research Database (Denmark)

    Allermann, Leila; Pejtersen, Jan; Gunnarsen, Lars Bo

    2007-01-01

    received a retrospective questionnaire about BRS (2301 respondents). Dust was collected from groups of offices and building characteristics were recorded. The potency of a dust sample to induce interleukin-8 (IL-8) secretion from the lung epithelial cell line A549 was measured as the slope of the initial...

  1. Nitroxide radical TEMPO reduces ozone-induced chemokine IL-8 production in lung epithelial cells

    Czech Academy of Sciences Publication Activity Database

    Castagna, R.; Davis, P.A.; Vasu, V.T.; Souček, Karel; Cross, C.E.; Greci, L.; Valacchi, G.

    2009-01-01

    Roč. 23, č. 3 (2009), s. 365-370 ISSN 0887-2333 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : interleukin-8 * ozone * lung epithelial cells Subject RIV: BO - Biophysics Impact factor: 2.060, year: 2009

  2. Kinetics of Intracellular, Extracellular and Production of Pro ...

    African Journals Online (AJOL)

    Keywords: Pro-inflammatory cytokine, Tumor necrosis factor-α, Interleukin-1α, Interleukin-1β,. Interleukin-6, Interleukin-8. Tropical Journal of ... retains neutrophils at sites of inflammation [6]. Many studies on the kinetics of cytokine ..... Lijnen P, Saavedra A, Petrov P. In vitro proliferative response of human peripheral blood ...

  3. The friendly bacteria within us Commensal bacteria of the intestine ...

    Indian Academy of Sciences (India)

    Short chain fatty acids (SCFA) are main source of energy for colonic epithelial cells · SCFA – role in colonic disease · SCFA prevent mucosal inflammation · Immunoregulation by gut bacteria · Balance of bacterial species in the gut · Immunosensory detection of intestinal bacteria · Pathogenic bacteria release interleukin-8 ...

  4. Cytokine filtration and adsorption during pre- and postdilution hemofiltration in four different membranes

    NARCIS (Netherlands)

    Bouman, C. S.; van Olden, R. W.; Stoutenbeek, C. P.

    1998-01-01

    In the present in vitro study we investigated filtration and adsorption of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) during predilution and postdilution hemofiltration with polysulfone, polyacrylonitrile, polyamide and cellulose triacetate membranes. The

  5. East African Medical Journal - Vol 90, No 2 (2013)

    African Journals Online (AJOL)

    Prevalence and Intensity of Single and Mixed Schistosoma mansoni and Schistosoma haematobium Infections in Primary School Children in Rachuonyo North ... Effects of Standard and/or Glutamine Dipeptide and/or Omega-3 Fatty Ascid-Supplemented Parenteral Nutrition on Neutrophil Functions, Interleukin-8 Level and ...

  6. Short Communication Single nucleotide polymorphisms in five ...

    African Journals Online (AJOL)

    Genetic diversity in candidate genes for fitness and production traits was explored in three populations of dairy cattle. The study focused on adipokines, including leptin (LEP), tumor necrosis factor alpha (TNF), interleukin-8 (IL8) and interleukin-10 (IL10) as candidate genes. The three populations of interest included young ...

  7. The strange connection between epidermal growth factor receptor tyrosine kinase inhibitors and dapsone: from rash mitigation to the increase in anti-tumor activity.

    Science.gov (United States)

    Boccellino, Mariarosaria; Quagliuolo, Lucio; Alaia, Concetta; Grimaldi, Anna; Addeo, Raffaele; Nicoletti, Giovanni Francesco; Kast, Richard Eric; Caraglia, Michele

    2016-11-01

    The presence of an aberrantly activated epidermal growth factor receptor (EGFR) in many epithelial tumors, due to its overexpression, activating mutations, gene amplification and/or overexpression of receptor ligands, represent the fundamental basis underlying the use of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Drugs inhibiting the EGFR have different mechanisms of action; while erlotinib and gefitinib inhibit the intracellular tyrosine kinase, monoclonal antibodies like cetuximab and panitumumab bind the extracellular domain of the EGFR both activating immunomediated anti-cancer effect and inhibiting receptor function. On the other hand, interleukin-8 has tumor promoting as well as neo-angiogenesis enhancing effects and several attempts have been made to inhibit its activity. One of these is based on the use of the old sulfone antibiotic dapsone that has demonstrated several interleukin-8 system inhibiting actions. Erlotinib typically gives a rash that has recently been proven to come out via up-regulated keratinocyte interleukin-8 synthesis with histological features reminiscent of typical neutrophilic dermatoses. In this review, we report experimental evidence that shows the use of dapsone to improve quality of life in erlotinib-treated patients by ameliorating rash as well as short-circuiting a growth-enhancing aspect of erlotinib based on increased interleukin-8 secretion.

  8. Characterizing microbiota-independent effects of oligosaccharides on intestinal epithelial cells

    NARCIS (Netherlands)

    Akbari, Peyman; Fink-Gremmels, Johanna; Willems, Rianne H.A.M.; Difilippo, Elisabetta; Schols, Henk A.; Schoterman, Margriet H.C.; Garssen, Johan; Braber, Saskia

    2017-01-01

    Purpose: The direct effects of galacto-oligosaccharides (GOS), including Vivinal® GOS syrup (VGOS) and purified Vivinal® GOS (PGOS), on the epithelial integrity and corresponding interleukin-8 (IL-8/CXCL8) release were examined in a Caco-2 cell model for intestinal barrier dysfunction. To

  9. Journal of Biosciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences. ZAKI ABU RABI. Articles written in Journal of Biosciences. Volume 42 Issue 2 June 2017 pp 265-274 Article. Interleukin 8 in progression of hormone-dependent early breast cancer · JELENA MILOVANOVIĆ NATAŠA TODOROVIĆ-RAKOVIĆ TIJANA VUJASINOVIĆ ZAKI ABU RABI.

  10. Inflammatory response to mucosal barrier injury after myeloablative therapy in allogeneic stem cell transplant recipients.

    NARCIS (Netherlands)

    Blijlevens, N.M.A.; Donnelly, J.P.; Pauw, B.E. de

    2005-01-01

    We noted a significant increase of interleukin-8 (IL-8), LBP and CRP mirroring the pattern of mucosal barrier injury as measured by gut integrity (lactulose/rhamnose ratio), daily mucositis score (DMS) and serum citrulline concentrations of 32 haematopoietic stem cell transplant (HSCT) recipients

  11. Cancer antigen 125: a bulk marker for the mesothelial mass in stable peritoneal dialysis patients

    NARCIS (Netherlands)

    Visser, C. E.; Brouwer-Steenbergen, J. J.; Betjes, M. G.; Koomen, G. C.; Beelen, R. H.; Krediet, R. T.

    1995-01-01

    Mesothelial cells that line the peritoneal cavity are capable of producing several proinflammatory cytokines such as interleukin-6 and interleukin-8. Since they are the most numerous cell in the peritoneal cavity when the lining mesothelial cells are included, they may play a major role in the local

  12. Arab Journal of Nephrology and Transplantation - Vol 6, No 1 (2013)

    African Journals Online (AJOL)

    Urinary Albumin and Interleukin-8 Levels are not Good Indicators of Ongoing Vesicoureteral Reflux in Children who have no Active Urinary Tract Infection · EMAIL FREE FULL TEXT EMAIL ... Chronic Renal Allograft Dysfunction: Risk Factors, Immunology and Prevention · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  13. Influence of diabetes on ambulation and inflammation in men and women with symptomatic peripheral artery disease

    Directory of Open Access Journals (Sweden)

    Andrew W. Gardner

    2015-12-01

    Conclusions: In patients with PAD, diabetic men and women with CAD had more severe claudication than their non-diabetic counterparts, as measured by shorter PWT, and the men had further ambulatory impairment manifested by slower 4-meter gait speed. Furthermore, the diabetic patients with CAD had elevations in interleukin-8, leptin, and PEDF.

  14. Canine pyometra: a model for the analysis of serum CXCL8 in inflammation

    OpenAIRE

    HAAS, Melanie; KAUP, Franz-Josef; NEUMANN, Stephan

    2015-01-01

    Interleukin-8 (IL-8 or CXCL8) is a highly selective pro-inflammatory chemokine, that is elevated in sera of humans and animals with various inflammatory diseases. CXCL8 is possibly involved in uncontrolled inflammation and the development of a systemic inflammatory response syndrome (SIRS) and sepsis. Nevertheless, its behavior and precise properties in the course of inflammation are not fully understood. Thus, we used naturally occurring canine pyometra as a model of inflammation, in order t...

  15. Interstitial concentrations of adipokines in subcutaneous abdominal and femoral adipose tissue

    DEFF Research Database (Denmark)

    Nielsen, Ninna Bo; Højbjerre, Lise; Sonne, Mette P

    2009-01-01

    Adipokines play important regulatory roles in the pathophysiology of obesity and insulin resistance. We measured plasma and interstitial concentrations of the adipokines adiponectin, resistin, leptin, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8...... plasma (approximately 100-fold, approximately 200-fold and approximately 1000-fold, respectively, PResistin concentrations did not differ significantly between compartments. Adipose tissue blood flow (ATBF) showed no regional difference (P>0.05). The intra- and inter-subject variations of all...

  16. Acute Pancreatitis as a Model to Predict Transition of Systemic Inflammation to Organ Failure in Trauma and Critical Illiness

    Science.gov (United States)

    2016-10-01

    interleukin-6 (IL-6), interleukin-8 (IL-8), Tumor Necrosis Factor-α (TNF-α), chemokine Monocyte Chemotactic Protein-1 (MCP-1), and the protein...activin at admission is a good marker for distinguishing cases which subsequently develop mild or severe AP (lower right panel AUC 0.820) A B C D...peer-reviewed articles or papers appearing in scientific, technical, or professional journals. Identify for each publication: Author(s); title

  17. Raised Proinflammatory Cytokine Production Within Cerebrospinal Fluid Precedes Fever Onset in Patients With Neurosurgery-Associated Bacterial Meningitis.

    Science.gov (United States)

    Liu, Zhuo-Hao; Tu, Po-Hsun; Chen, Nan-Yu; Yip, Ping K; Bowes, Amy L; Lee, Cheng-Chi; Chan, She-Hung; Kung, Chua-Chi; Wang, Alvin Yi-Chou; Wu, Chieh-Tsai; Lee, Shih-Tseng

    2015-11-01

    The objective of the present study was to determine whether selective inflammatory cytokine concentrations within cerebrospinal fluid are useful markers for the differential diagnosis of aseptic and bacterial meningitis within neurosurgical patients. Prospective, open-label, observational, cohort study. Neurosurgical ICU, Chang Gung Memorial Hospital. Thirty-two consecutive neurosurgical patients who had postoperative fever following external ventricular drain insertion for the treatment of brain injury underwent serial cerebrospinal fluid cytokine analysis pre and post fever to determine the value of such markers in ascertaining the differential diagnosis of meningitis. Cerebrospinal fluid samples were collected on the day of fever onset, as well as on day 2 and 4 pre and post fever development. Tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-8, transforming growth factor-β, and procalcitonin were subsequently analyzed using enzyme-linked immunosorbent assay analysis techniques. Inflammatory marker levels were compared among febrile aseptic, bacterial, and nonmeningitis patients to determine cerebrospinal fluid inflammatory changes over time. Significant increases in cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, interleukin-6, and interleukin-8 levels were observed within patients with bacterial meningitis at fever onset, which was not evident in aseptic or nonmeningitis patients. Furthermore, significant increases in cerebrospinal fluid tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8 levels were detected as early as 4 days prior to fever onset within patients with bacterial meningitis when compared with both aseptic and nonmeningitis groups. Interestingly, procalcitonin was only significantly increased in patients with bacterial meningitis on the fourth day post fever. The present study suggests that raised cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, and interleukin-8 in a

  18. Local and systemic effects of fibrin and cyanoacrylate adhesives on lung lesions in rabbits

    Directory of Open Access Journals (Sweden)

    Marcus V.H. Carvalho

    Full Text Available OBJECTIVES: Tissue adhesives can be used to prevent pulmonary air leaks, which frequently occur after lung interventions. The objective of this study is to evaluate local and systemic effects of fibrin and cyanoacrylate tissue adhesives on lung lesions in rabbits. METHODS: Eighteen rabbits were submitted to videothoracoscopy + lung incision alone (control or videothoracoscopy + lung incision + local application of fibrin or cyanoacrylate adhesive. Blood samples were collected and assessed for leukocyte, neutrophil and lymphocyte counts and interleukin-8 levels preoperatively and at 48 hours and 28 days post-operatively. After 28 days, the animals were euthanized for gross examination of the lung surface, and lung fragments were excised for histopathological analysis. RESULTS: Fibrin and cyanoacrylate produced similar adhesion scores of the lung to the parietal pleura. Microscopic analysis revealed uniform low-cellular tissue infiltration in the fibrin group and an intense tissue reaction characterized by dense inflammatory infiltration of granulocytes, giant cells and necrosis in the cyanoacrylate group. No changes were detected in the leukocyte, neutrophil or lymphocyte count at any time-point, while the interleukin-8 levels were increased in the fibrin and cyanoacrylate groups after 48 hours compared with the pre-operative control levels (p<0.01. CONCLUSION: Both adhesive agents promoted normal tissue healing, with a more pronounced local inflammatory reaction observed for cyanoacrylate. Among the serum markers of inflammation, only the interleukin-8 levels changed post-operatively, increasing after 48 hours and decreasing after 28 days to levels similar to those of the control group in both the fibrin and cyanoacrylate groups.

  19. Assessment of the probiotic potential of a dairy product fermented by Propionibacterium freudenreichii in piglets.

    Science.gov (United States)

    Cousin, Fabien J; Foligné, Benoît; Deutsch, Stéphanie-Marie; Massart, Sébastien; Parayre, Sandrine; Le Loir, Yves; Boudry, Gaëlle; Jan, Gwénaël

    2012-08-15

    Dairy propionibacteria, including Propionibacterium freudenreichii , display promising probiotic properties, including immunomodulation. These properties are highly strain-dependent and rarely studied in a fermented dairy product. We screened 10 strains, grown in a newly developed fermented milk ultrafiltrate, for immunomodulatory properties in vitro. The most anti-inflammatory strain, P. freudenreichii BIA129, was further tested on piglets. P. freudenreichii -fermented product improved food intake and growth of piglets. Colonic mucosa explants of treated pigs secreted less interleukin 8 (-25%, P dairy propionibacteria-fermented products, which are promising for the prevention or healing of inflammatory bowel diseases.

  20. Agonists and inverse agonists for the herpesvirus 8-encoded constitutively active seven-transmembrane oncogene product, ORF-74

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Kledal, T N; Bräuner-Osborne, Hans

    1999-01-01

    A number of CXC chemokines competed with similar, nanomolar affinity against 125I-interleukin-8 (IL-8) binding to ORF-74, a constitutively active seven-transmembrane receptor encoded by human herpesvirus 8. However, in competition against 125I-labeled growth-related oncogene (GRO)-alpha, the ORF-74...... receptor was highly selective for GRO peptides, with IL-8 being 10,000-fold less potent. The constitutive stimulating activity of ORF-74 on phosphatidylinositol turnover was not influenced by, for example, IL-8 binding. In contrast, GRO peptides acted as potent agonists in stimulating ORF-74 signaling...

  1. Well-Defined Degradable Cationic Polylactide as Nanocarrier for the Delivery of siRNA to Silence Angiogenesis in Prostate Cancer

    OpenAIRE

    Chen, Chih-Kuang; Law, Wing-Cheung; Aalinkeel, Ravikumar; Nair, Bindukumar; Kopwitthaya, Atcha; Mahajan, Supriya D.; Reynolds, Jessica L.; Zou, Jiong; Schwartz, Stanley A.; Prasad, Paras N.; Cheng, Chong

    2012-01-01

    Well-defined tertiary amine-functionalized cationic polylactides (CPLAs) are synthesized by thiol-ene click functionalization of an allyl-functionalized polylactide, and utilized here for the delivery of interleukin-8 (IL-8) siRNA via CPLA-IL-8 siRNA nanoplexes. The CPLAs possess remarkable hydrolytic degradability, and their cytotoxicity is relatively low. The CPLA-IL-8 siRNA nanoplexes can be readily taken up by prostate cancer cells, resulting in significant IL-8 gene silencing. It is foun...

  2. The Vibrio parahaemolyticus Type III Secretion Systems manipulate host cell MAPK for critical steps in pathogenesis.

    LENUS (Irish Health Repository)

    Matlawska-Wasowska, Ksenia

    2010-12-01

    Vibrio parahaemolyticus is a food-borne pathogen causing inflammation of the gastrointestinal epithelium. Pathogenic strains of this bacterium possess two Type III Secretion Systems (TTSS) that deliver effector proteins into host cells. In order to better understand human host cell responses to V. parahaemolyticus, the modulation of Mitogen Activated Protein Kinase (MAPK) activation in epithelial cells by an O3:K6 clinical isolate, RIMD2210633, was investigated. The importance of MAPK activation for the ability of the bacterium to be cytotoxic and to induce secretion of Interleukin-8 (IL-8) was determined.

  3. The ScpC Protease of Streptococcus pyogenes Affects the Outcome of Sepsis in a Murine Model ▿

    OpenAIRE

    Sjölinder, Hong; Lövkvist, Lena; Plant, Laura; Eriksson, Jens; Aro, Helena; Jones, Allison; Jonsson, Ann-Beth

    2008-01-01

    The ScpC protease of Streptococcus pyogenes degrades interleukin-8 (IL-8), a chemokine that mediates neutrophil transmigration and activation. The ability to degrade IL-8 differs dramatically among clinical isolates of S. pyogenes. Bacteria expressing ScpC overcome immune clearance by preventing the recruitment of neutrophils in soft tissue infection of mice. To study the role of ScpC in streptococcal sepsis, we generated an ScpC mutant that did not degrade IL-8 and thus failed to prevent the...

  4. Predictors of Airway Hyperresponsiveness in Elite Athletes

    DEFF Research Database (Denmark)

    Toennesen, Louise L; Porsbjerg, Celeste; Pedersen, Lars

    2015-01-01

    INTRODUCTION: Elite athletes frequently experience asthma and airway hyperresponsiveness (AHR). We aimed to investigate predictors of airway pathophysiology in a group of unselected elite summer-sport athletes, training for the summer 2008 Olympic Games, including markers of airway inflammation......, systemic inflammation, and training intensity. METHODS: Fifty-seven Danish elite summer-sport athletes with and without asthma symptoms all gave a blood sample for measurements of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF...

  5. Effectiveness of flossing loops in the control of the gingival health

    OpenAIRE

    Azcarate-Vel?zquez, Francisco; Garrido-Serrano, Roberto; Castillo-Dal?, Gabriel; Serrera-Figallo, Mar?a-Angeles; Ga??n-Calvo, Alfonso; Torres-Lagares, Daniel

    2017-01-01

    Background One of the key factor in the good condition of periodontal tissues is their daily hygiene. Oral hygiene techniques such brushing and a good interdental hygiene by correct flossing are very important. The aim of this study is to compare the use of dental floss in a loop vs traditional floss in the control of Loe-Silness Gingival Index (IG), Turesky?s Plaque Index (IPT), Gingival Bleeding Index (IS) and the values of interleukin 6 (IL-6) and interleukin 8 (IL-8). Material and Methods...

  6. Aerosol challenge of calves with Haemophilus somnus and Mycoplasma dispar

    DEFF Research Database (Denmark)

    Tegtmeier, C.; Angen, Øystein; Grell, S.N.

    2000-01-01

    , the ability of H. somnus and M. dispar to act as primary pathogens under these conditions were minimal and inconsistent. However, a transient rise in body temperature, a marked granulocytosis and increased levels of interleukin-8 in peripheral blood after inoculation with H. somnus indicated a clear systemic...... investigated by recording clinical data, cytokine expression of peripheral blood cells and pathology. Twelve calves were included in the study: Three animals were exposed to H. somnus only, and two to M. dispar only, whereas five were challenged to M. dispar followed by exposure to H. somnus 11-14 days later...

  7. Expression of Inflammation-Related Genes Is Altered in Gastric Tissue of Patients with Advanced Stages of NAFLD

    Directory of Open Access Journals (Sweden)

    Rohini Mehta

    2013-01-01

    Full Text Available Obesity is associated with chronic low-grade inflammation perpetuated by visceral adipose. Other organs, particularly stomach and intestine, may also overproduce proinflammatory molecules. We examined the gene expression patterns in gastric tissue of morbidly obese patients with nonalcoholic fatty liver disease (NAFLD and compared the changes in gene expression in different histological forms of NAFLD. Stomach tissue samples from 20 morbidly obese NAFLD patients who were undergoing sleeve gastrectomy were profiled using qPCR for 84 genes encoding inflammatory cytokines, chemokines, their receptors, and other components of inflammatory cascades. Interleukin 8 receptor-beta (IL8RB gene overexpression in gastric tissue was correlated with the presence of hepatic steatosis, hepatic fibrosis, and histologic diagnosis of nonalcoholic steatohepatitis (NASH. Expression levels of soluble interleukin 1 receptor antagonist (IL1RN were correlated with the presence of NASH and hepatic fibrosis. mRNA levels of interleukin 8 (IL8, chemokine (C-C motif ligand 4 (CCL4, and its receptor chemokine (C-C motif receptor type 5 (CCR5 showed a significant increase in patients with advanced hepatic inflammation and were correlated with the severity of the hepatic inflammation. The results of our study suggest that changes in expression patterns for inflammatory molecule encoding genes within gastric tissue may contribute to the pathogenesis of obesity-related NAFLD.

  8. The Effects of Isoflavone Supplementation Plus Combined Exercise on Lipid Levels, and Inflammatory and Oxidative Stress Markers in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Jéssica S. Giolo

    2018-03-01

    Full Text Available This study tested the effect of isoflavone supplementation in addition to combined exercise training on plasma lipid levels, inflammatory markers and oxidative stress in postmenopausal women. Thirty-two healthy and non-obese postmenopausal women without hormone therapy were randomly assigned to exercise + placebo (PLA; n = 15 or exercise + isoflavone supplementation (ISO; n = 17 groups. They performed 30 sessions of combined exercises (aerobic plus resistance over ten weeks and consumed 100 mg of isoflavone supplementation or placebo. Blood samples were collected after an overnight fast to analyze the lipid profile, interleukin-6 (IL-6, interleukin-8 (IL-8, superoxide dismutase (SOD, total antioxidant capacity (FRAP, and thiobarbituric acid reactive substances (TBARS, before and after ten weeks of the intervention. There were no differences in the changes (pre vs. post between groups for any of the inflammatory markers, oxidative stress markers or lipid profile variables. However, interleukin-8 was different between pre- and post-tests (p < 0.001 in both groups (Δ = 7.61 and 5.61 pg/mL as were cholesterol levels (p < 0.05, with no interaction between groups. The combination of isoflavone supplementation and exercise training did not alter oxidative stress markers in postmenopausal women, but exercise training alone may increase IL-8 and decrease total cholesterol levels.

  9. Effect of an intraosseous injection of depo-medrol on pulpal concentrations of PGE2 and IL-8 in untreated irreversible pulpitis.

    Science.gov (United States)

    Isett, James; Reader, Al; Gallatin, Eric; Beck, Mike; Padgett, David

    2003-04-01

    The purpose of this prospective, randomized, double-blind study was to evaluate the pulpal concentrations of prostaglandin E2 (PGE2) and interleukin-8 (IL-8) in untreated teeth with irreversible pulpitis after the administration of an intraosseous injection of Depo-Medrol. Forty emergency patients with a clinical diagnosis of irreversible pulpitis experiencing moderate to severe pain participated. After receiving local anesthesia, patients randomly received, in a double-blind manner, an intraosseous injection of either 1 ml of Depo-Medrol (40 mg) (20 patients) or 1 ml of sterile saline placebo (control) (20 patients). No endodontic treatment was initiated. At 1 or 3 days after the intraosseous injection, the teeth were extracted and the pulpal tissue harvested. Prostaglandin E2 and interleukin-8 concentrations were determined by enzyme immunoassay. Results demonstrated a significantly (p concentration of prostaglandin E2 compared to the saline group at day 1. There were no significant (p > 0.05) differences between the two groups at day 3. The pulpal concentrations of prostaglandin E2 were reduced at 1 day after the intraosseous injection of Depo-Medrol.

  10. Serum cytokine and chemokine profiles in neonates with meconium aspiration syndrome.

    Science.gov (United States)

    Okazaki, Kaoru; Kondo, Masatoshi; Kato, Masahiko; Kakinuma, Ryota; Nishida, Akira; Noda, Masahiro; Taniguchi, Kiyosu; Kimura, Hirokazu

    2008-04-01

    Various inflammatory cytokines and chemokines are thought to be associated with the pathophysiology of meconium aspiration syndrome. To clarify any such association, we compared various serum cytokine and chemokine profiles in patients with and without meconium aspiration syndrome. Using a highly sensitive fluorescence microsphere method, 17 types of cytokines and chemokines in sera were measured in 11 neonatal patients with meconium aspiration syndrome, 16 neonatal patients without meconium aspiration syndrome, and 9 healthy children. The concentrations of 8 types of proinflammatory cytokines and chemokines were significantly higher in the meconium aspiration syndrome group than in healthy controls: interleukin-1beta, interleukin-6, interleukin-8, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interferon-gamma, macrophage inflammatory protein-1beta, and tumor necrosis factor-alpha. Six types of proinflammatory cytokines and chemokines were significantly higher in the meconium aspiration syndrome group than in the nonmeconium aspiration syndrome group: interleukin-6, interleukin-8, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha. Serum concentrations of interleukin-10 (anti-inflammatory cytokine) in the meconium aspiration syndrome group were higher than those in both the nonmeconium aspiration syndrome group and healthy children group (P = .007 and 0.001, respectively). Most types of proinflammatory cytokines and chemokines in sera of neonates with meconium aspiration syndrome were higher than those without meconium aspiration syndrome, giving support to the suggestion that elevated levels are associated with the pathogenesis of meconium aspiration syndrome.

  11. Thalidomide increases human keratinocyte migration and proliferation.

    Science.gov (United States)

    Nasca, M R; O'Toole, E A; Palicharla, P; West, D P; Woodley, D T

    1999-11-01

    Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behçet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 microM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2. 5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.

  12. Effectiveness of flossing loops in the control of the gingival health.

    Science.gov (United States)

    Azcarate-Velázquez, Francisco; Garrido-Serrano, Roberto; Castillo-Dalí, Gabriel; Serrera-Figallo, María-Angeles; Gañán-Calvo, Alfonso; Torres-Lagares, Daniel

    2017-06-01

    One of the key factor in the good condition of periodontal tissues is their daily hygiene. Oral hygiene techniques such brushing and a good interdental hygiene by correct flossing are very important. The aim of this study is to compare the use of dental floss in a loop vs traditional floss in the control of Loe-Silness Gingival Index (IG), Turesky´s Plaque Index (IPT), Gingival Bleeding Index (IS) and the values of interleukin 6 (IL-6) and interleukin 8 (IL-8). A comparative study of 40 patients in which each patient was his own control, using during 45 days each one of the devices (new loop floss and conventional floss) of interdental hygiene analysed. Data for Loe-Silness Gingival Index (IG), Turesky´s Plaque Index (IPT), Gingival Bleeding Index (IS) and the values of interleukin 6 (IL-6) and interleukin 8 (IL-8)were collected and measured in every visit for every type of interdental hygiene device. Our data indicates that the rate of Turesky´s Plaque Index presented statistically significant differences between groups (loop: 1.66 ± 0.8; traditional: 1.12 ± 0.8; p dental floss designs try to make their use easier and more sensitive, and plaque removal more effective. The loop design can facilitate interdental hygiene, reaching similar effectiveness than traditional floss, improving some indicators, such as Turesky´s Plaque Index. Key words: Dental floss, bacterial plaque, loop floss, plaque index, periodontal diseases.

  13. Live Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis activate the inflammatory response trhough Toll-like receptors 2, 4, and 9 in species-specific patterns

    DEFF Research Database (Denmark)

    Mogensen, T.H.; Paludan, Søren Riis; Kilian, Mogens

    2006-01-01

    activation by live bacteria. Here, we demonstrate that live Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis, the three principal causes of bacterial meningitis, use distinct sets of TLRs to trigger the inflammatory response. Using human embryonic kidney 293 cell lines......, each overexpressing one type of TLR, we found that S. pneumoniae triggered activation of the transcription factor nuclear factor-kappaB and expression of interleukin-8, only in cells expressing TLR2 or -9. The same response was evoked by H. influenzae in cells expressing TLR2 or -4 and by N...... and confirmed the essential role of these TLRs and also identified differential functions of TLRs in activation of the inflammatory response. Collectively, we here demonstrate that S. pneumoniae, H. influenzae, and N. meningitidis each activate several TLRs in species-specific patterns and show that infection...

  14. New methods and reagents to improve the ferret model for human influenza infections

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Kirkeby, Svend; Aasted, Bent

    The ferret has been extensively used to study human influenza infections. However, its value as a model has suffered from the limited set of reagents and methods available for this animal. We have recently tested a large number of monoclonal antibodies cross-reacting with ferret CD markers (CD8, CD......9, CD14, CD18, CD25, CD29, CD32, CD44, CD61, CD71, CD79b, CD88, CD104, CD172a and CD3) and cytokines (interferon-gamma, TNF-alpha, interleukine-4 and interleukine-8) for flow cytometry , as well as polyclonal antibodies cross-reacting with ferret immunoglobulins (IgA, IgG and IgM) for ELISA. Further...... improvements of the model will aim at establishing a reliable RT-PCR for ferret cytokines, as well as investigating the location of influenza receptors and viral particles in the upper and lower respiratory tract via immunohistochemistry...

  15. Peripheral blood collection

    DEFF Research Database (Denmark)

    Franken, Carmen; Remy, Sylvie; Lambrechts, Nathalie

    2016-01-01

    - and glucocorticoid-mediated networks, and specifically interleukin-8 (IL-8). These findings suggest that even short bench times affect gene expression, requiring to carry out blood collection in a strictly standardized way. © 2016 Informa UK Limited, trading as Taylor & Francis Group.......A crucial challenge for gene expression analysis in human biomonitoring studies on whole blood samples is rapid sample handling and mRNA stabilization. This study was designed to evaluate the impact of short bench times (less than 30 min) on yield, quality and gene expression of m......RNA in the presence of different stabilization buffers (TempusTM Blood RNA tube and RNAlater® Stabilization Reagent). Microarray analyzes showed significant changes over short periods of time in expression of a considerate part of the transcriptome (2356 genes) with a prominent role for NFкB-, cancer...

  16. Studies on the Biological Effects of Ozone: 10. Release of Factors from Ozonated Human Platelets

    Directory of Open Access Journals (Sweden)

    G. Valacchi

    1999-01-01

    Full Text Available In a previous work we have shown that heparin, in the presence of ozone (O3, promotes a dose-dependent platelet aggregation, while after Ca2+ chelation with citrate, platelet aggregation is almost negligible. These results led us to think that aggregation may enhance the release of platelet components. We have here shown that indeed significantly higher amount of platelet-derived growth factor (PDGF, transforming growth factor β1 (TGF-β1 and interleukin-8(IL-8 are released in a dose-dependent manner after ozonation of heparinised platelet-rich plasma samples. These findings may explain the enhanced healing of torpid ulcers in patients with chronic limbischemia treated with O3 autohaemoteraphy (O3-AHT.

  17. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus

    Science.gov (United States)

    Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

    2014-01-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions. PMID:25317156

  18. [Cytomorphological analysis of remodeling of the bronchial wall in different types of bronchial asthma].

    Science.gov (United States)

    Gereng, E A; Sukhodolo, I V; Pleshko, R I; Ogorodova, L M; Selivanova, P A; Dziuman, A N

    2012-01-01

    The objective of the present work was to search for the tissue and cellular markers of remodeling of bronchial mucosa in the patients with different clinical forms of bronchial asthma (BA). The use of up-to-date morphometric techniques has demonstrated that mild and moderately severe forms of bronchial asthma are accompanied by the development of Th2-immune response associated with increased production of interleukin-4 and marked degranulation of eosinophilic granulocytes resulting in desquamation of epithelium and goblet cell hyperplasia. The severe BA phenotype of "chronic asthma with fixed obstruction" is associated with the development of non-atopic inflammation in the bronchial mucous membrane that manifests itself as the increased concentration of interleukin-8 in bronchial mucosa and its neutrophilic infiltration leading to the development of pronounced subepithelial fibrosis, thickening of the basal membrane, and atrophy of epithelium. Specific structural changes in bronchial mucosa of the patients presenting with BA underlie functional disturbances that cause severe bronchial obstructive syndrome.

  19. Hypoadiponectinemia in overweight children contributes to a negative metabolic risk profile 6 years later

    DEFF Research Database (Denmark)

    Kynde, Iben; Heitmann, Berit L; Bygbjerg, Ib C

    2009-01-01

    -density lipoprotein cholesterol ratio, serum triglycerides, systolic blood pressure, and the reciprocal value of fitness (maximum watts per kilogram). Overweight was defined using international classification of body mass index cutoff points for children. Plasma adiponectin, leptin, interleukin-8, and hepatocyte...... growth factor were assessed using immunochemical assays. Linear relationships were found between metabolic risk score and both plasma adiponectin (inverse, P = .02) and plasma leptin (P overweight but not normal-weight children, plasma...... adiponectin at baseline was inversely associated with metabolic risk score 6 years later (P = .04). In childhood, both hypoadiponectinemia and hyperleptinemia accompany a negative metabolic risk profile. In addition, circulating plasma adiponectin may be a useful biomarker to identify overweight children...

  20. The immune response is affected for at least three weeks after extensive surgery for ovarian cancer

    DEFF Research Database (Denmark)

    Brøchner, Anne Craveiro; Mikkelsen, Søren; Hegelund, Iørn

    2016-01-01

    INTRODUCTION: The treatment of women with ovarian cancer in advanced stages consists of extensive surgery followed by chemotherapy initiated three weeks after surgery. In this study, selected immune parameters were investigated to elucidate when the immune system is normalised following...... the operation. METHODS: Ten women undergoing extensive surgery for ovarian cancer were compared with a control group of ten women undergoing abdominal hysterectomy for a benign diagnosis. Blood samples were collected over a period of 21 days post-operatively. The levels of interleukin-6, interleukin-8...... activity of natural killer-cells did not normalise within 21 days. CONCLUSIONS: The level of the cytokines interleukin-6 and interleukin-10 is increased 21 days after the operation, and the function of natural killer cells is not normalised at 21 days after surgery. FUNDING: The study received funding from...

  1. Isolation and identification of Malassezia species from Chinese and Korean patients with seborrheic dermatitis and in vitro studies on their bioactivity on sebaceous lipids and IL-8 production.

    Science.gov (United States)

    Kim, Soo Young; Kim, Se Hyun; Kim, Su Na; Kim, Ah-Reum; Kim, Yu Ri; Kim, Min Jung; Park, Won-Seok; Lee, John Hwan; Jung, Won Hee; Lee, Yang Won; Choe, Yong Beom; Ahn, Kyu Joong

    2016-05-01

    We investigated the distribution of Malassezia yeast in 120 Chinese (20 patients from each of six cities) and 20 Korean patients with scalp seborrheic dermatitis (SD) and dandruff (SD/D) using ITS1 and ITS2 polymerase chain reaction-restriction fragment length polymorphism. Bioactivity was studied by quantifying sebum lipid production by human primary sebocytes and inflammatory cytokine, interleukin-8 (IL-8) production was studied by exposing HaCaT keratinocytes with extracts of five standard Malassezia strains; M. globosa, M. restricta, M. sympodialis, M. dermatis and M. slooffiae. M. restricta and M. globosa were the most frequently encountered species from both Chinese and Korean patients. These two Malassezia species also promoted neutral lipid synthesis although the result was not statistically significant and induced significant increase in IL-8 production among the five Malassezia species studied. The study suggests a possible role of these organisms in the pathogenesis of SD/D. © 2016 Blackwell Verlag GmbH.

  2. Milk enzyme activities and subclinical mastitis among women in Guinea-Bissau

    DEFF Research Database (Denmark)

    Rasmussen, Lill Brith Wium; Hartvig, Ditte Luise; Kæstel, Pernille

    2008-01-01

    Background: Subclinical mastititis (SCM) is a condition with raised milk concentration of sodium and milk immune factors. The milk enzymes N-acetyl-β-D-glucosaminidase (NAGase), lactate dehydrogenase (LDH), acid phosphatase (AcP), and alkaline phosphatase (AP) have attracted attention in dairy...... research as indicators of SCM, udder health, and milk quality. Study Design: To investigate if milk enzyme activities and the inflammatory interleukin 8 (IL-8) level are increased in women with SCM, we measured sodium, potassium, NAGase, LDH, AcP, AP, and IL-8 in breastmilk samples collected at 2 months...... in univariate linear regression (p enzymes and IL-8). Conclusions: A positive association between the Na/K ratio and the breastmilk enzymes NAGase, LDH, AcP, and AP was found. Breastmilk enzymes have not previously been investigated in relation to SCM in women, and further...

  3. Twelve potential fibrosis markers to differentiate mild liver fibrosis from cirrhosis in patients infected with chronic hepatitis C genotype 1

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Ruhwald, M; Moessner, B

    2011-01-01

    Information about the stage of liver fibrosis is important for managing patients with chronic hepatitis C (CHC). The aim of this study was to evaluate 12 plasma markers for differentiating no/mild liver fibrosis from cirrhosis among patients with CHC genotype 1. Transient elastography was used...... to assess the stage of fibrosis for the patients included in the study. Forty patients were included (21 cirrhotic). Plasma levels of tumor necrosis factor-a (TNF-a), interleukin 8 (IL-8), interferon-¿ inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), soluble urokinase-type plasminogen....... In conclusion, several of the investigated markers showed promise for differentiating cirrhosis from no/mild fibrosis among patients with CHC genotype 1....

  4. [Mechanism behind streptococcus toxic shock-like syndrome onset--immune evasion and bacterial properties].

    Science.gov (United States)

    Ikebe, Tadayoshi; Ato, Manabu; Kobayashi, Kazuo; Watanabe, Haruo

    2009-09-01

    Streptococcal toxic shock-like syndrome (STSS) was firstly reported in 1987 in the United States. Japan's first definitive STSS case was reported in 1992, with over 500 cases since confirmed. Mortality is extremely high at 40%. Pathological findings, bacteria aggregation, and a paucity of polymorphonuclear neutrophils (PMN) in the foci of invasive group A streptococcal (GAS) infection suggest that host defense disturbance plays an important role in invasive infection onset. GAS, clinically isolated from severely invasive, but not from non-invasive, infections, could compromise human PMN functions in at least two independent ways-by inducing necrosis to PMN by enhanced production of pore-forming toxin streptolysin O (SLO) and by PMN migration impairment via digesting interleukin-8, a PMN attracting chemokine, through increased serine protease ScpC production. Expression of these genes was upregulated by a loss of repressive function with the csrS gene mutation of the two-component sensor/regulator system.

  5. The LasB Elastase of Pseudomonas aeruginosa Acts in Concert with Alkaline Protease AprA To Prevent Flagellin-Mediated Immune Recognition.

    Science.gov (United States)

    Casilag, Fiordiligie; Lorenz, Anne; Krueger, Jonas; Klawonn, Frank; Weiss, Siegfried; Häussler, Susanne

    2016-01-01

    The opportunistic pathogen Pseudomonas aeruginosa is capable of establishing severe and persistent infections in various eukaryotic hosts. It encodes a wide array of virulence factors and employs several strategies to evade immune detection. In the present study, we screened the Harvard Medical School transposon mutant library of P. aeruginosa PA14 for bacterial factors that modulate interleukin-8 responses in A549 human airway epithelial cells. We found that in addition to the previously identified alkaline protease AprA, the elastase LasB is capable of degrading exogenous flagellin under calcium-replete conditions and prevents flagellin-mediated immune recognition. Our results indicate that the production of two proteases with anti-flagellin activity provides a failsafe mechanism for P. aeruginosa to ensure the maintenance of protease-dependent immune-modulating functions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Controlled exposure to diesel exhaust and traffic noise - Effects on oxidative stress and activation in mononuclear blood cells

    DEFF Research Database (Denmark)

    Hemmingsen, Jette Gjerke; Møller, Peter; Jantzen, Kim

    2015-01-01

    exhaust (DE) at 276μg/m(3) from a passenger car or filtered air, with co-exposure to traffic noise at 48 or 75dB(A). Gene expression markers of inflammation, (interleukin-8 and tumor necrosis factor), oxidative stress (heme oxygenase (decycling-1)) and DNA repair (8-oxoguanine DNA glycosylase (OGG1)) were...... unaltered in peripheral blood mononuclear cells (PBMCs). No significant differences in DNA damage levels, measured by the comet assay, were observed after DE exposure, whereas exposure to high noise levels was associated with significantly increased levels of hOGG1-sensitive sites in PBMCs. Urinary levels...... of 8-oxo-7,8-dihydro-2'-deoxyguanosine were unaltered. In auxiliary ex vivo experiments whole blood was incubated with particles from the exposure chamber for 3h without effects on DNA damage in PBMCs or intracellular reactive oxygen species production and expression of CD11b and CD62L adhesion...

  7. Prioritization of Susceptibility Genes for Ectopic Pregnancy by Gene Network Analysis

    Science.gov (United States)

    Liu, Ji-Long; Zhao, Miao

    2016-01-01

    Ectopic pregnancy is a very dangerous complication of pregnancy, affecting 1%–2% of all reported pregnancies. Due to ethical constraints on human biopsies and the lack of suitable animal models, there has been little success in identifying functionally important genes in the pathogenesis of ectopic pregnancy. In the present study, we developed a random walk–based computational method named TM-rank to prioritize ectopic pregnancy–related genes based on text mining data and gene network information. Using a defined threshold value, we identified five top-ranked genes: VEGFA (vascular endothelial growth factor A), IL8 (interleukin 8), IL6 (interleukin 6), ESR1 (estrogen receptor 1) and EGFR (epidermal growth factor receptor). These genes are promising candidate genes that can serve as useful diagnostic biomarkers and therapeutic targets. Our approach represents a novel strategy for prioritizing disease susceptibility genes. PMID:26840308

  8. Comparisons of IL-8, ROS and p53 responses in human lung epithelial cells exposed to two extracts of PM2.5 collected from an e-waste recycling area, China

    Science.gov (United States)

    Yang, Fangxing; Jin, Shiwei; Xu, Ying; Lu, Yuanan

    2011-04-01

    To identify the different effects of organic-soluble and water-soluble pollutants adsorbed on PM2.5 (PM: particulate matter) released from e-waste (electrical/electronic waste) on inflammatory response, oxidative stress and DNA damage, interleukin-8 (IL-8), reactive oxygen species (ROS) and p53 protein levels were determined and compared in human lung epithelial A549 cells exposed to extracts of PM2.5 collected from two sampling sites in an e-waste recycling area in China. It is found that both extracts induced increases of IL-8 release, ROS production and p53 protein expression. The differences between the organic-soluble and water-soluble extracts were determined as of significance for ROS production (p e-waste recycling areas could lead to inflammatory response, oxidative stress and DNA damage, and the organic-soluble extracts had higher potential to induce such adverse effects on human health.

  9. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus.

    Science.gov (United States)

    Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

    2014-08-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions.

  10. Two Neisseria meningitidis strains with different ability to stimulate toll-like receptor 4 through the MyD88-independent pathway

    DEFF Research Database (Denmark)

    Mogensen, T.H.; Paludan, Søren Riis; Kilian, Mogens

    2006-01-01

    Neisseria meningitidis causes acute severe diseases, including sepsis and meningitis, and more benign manifestations such as chronic meningococcemia or colonization of the upper respiratory tract. The inflammatory response, which contributes to the pathogenesis of meningococcal disease......, is initiated by pattern recognition receptors, among which Toll-like receptors (TLR)s have been ascribed a particularly important role. We have previously demonstrated that N. meningitidis induce proinflammatory cytokine expression through TLR2 and TLR4. Here we characterize the molecular basis...... for differential activation of the inflammatory response by two N. meningitidis strains. This difference was due to differential ability to activate signal transduction through TLR4, as HEK293 cells expressing TLR4 produced significantly different levels of interleukin-8 in response to these strains. At the level...

  11. Immunological disorders in formation of periodontal diseases at pregnant women

    Directory of Open Access Journals (Sweden)

    A.V. Lepilin

    2010-06-01

    Full Text Available The research goal is to study clinical and immunological features of parodentium and cytokine profile in oral cavity of pregnant women. The condition of parodentium tissues was studied at 200 women with physiological pregnancy and 300 women with pregnancy complicated by gestosis. According to the results of examination 50 women with gestosis and 50 women with physiological pregnancy had inflammatory periodontal diseases. Phenotyping of lymphocytes by immunofluorescence method, investigation of necrosis containing factor of tumour-a, interleukin-8, interleukin-4 and transforming growth factor beta-1 in oral cavity by immunofermental analysis were performed. Frequency and character of inflammatory periodontal diseases at pregnancy were defined. Correlation of gingivitis and periodontitis at pregnancy with extragenital pathology was demonstrated. Immune and cytokine disbalance contributed greatly to pathogenesis of inflammatory periodontal diseases at pregnant women. Thus pathogenesis of oral hygiene, smoking, gestosis, immunosuppression and cytokine disbalance affects inflammatory periodontal diseases at pregnant women

  12. Clinical and experimental studies on inflammatory mediators during AIDS-associated Pneumocystis carinii pneumonia

    DEFF Research Database (Denmark)

    Benfield, Thomas

    2003-01-01

    , National Institutes of Health, Bethesda, Maryland, USA. Pneumocystis carinii pneumonia (PCP) is the most frequent AIDS defining illness over the past 20 years. PCP is associated with considerable morbidity and mortality. An inflammatory reaction to P. carinii is believed to cause respiratory failure...... markers. Bronchoalveolar lavage (BAL) neutrophilia has been associated with disease severity, and an increased risk of death from PCP. Through competitive inhibitory studies, we showed that BAL fluid neutrophil chemotactic activity largely was explained by the presence of interleukin-8 (IL-8). Further, we...... showed a correlation between high levels of BAL fluid IL-8 and mortality. Adjuvant treatment with glucocorticosteroids lowered BAL fluid IL-8 levels. In experimental studies we found that P. carinii Major Surface Antigen (MSG) induced IL-8 and tumor necrosis factor-alpha secretion from human monocytes...

  13. Cytokine levels in the preterm infant with neonatal intestinal injury.

    Science.gov (United States)

    Bhatia, Amina M; Stoll, Barbara J; Cismowski, Mary J; Hamrick, Shannon E

    2014-06-01

    The purpose of this study is to characterize the cytokine response of preterm newborns with surgical necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP) before surgical treatment and to relate these finding to intestinal disease (NEC vs. SIP). The study was a 14-month prospective, cohort study of neonates undergoing surgery or drainage for NEC or SIP or surgical ligation of patent ductus arteriosus (PDA). Multiplex cytokine detection technology was used to analyze six inflammatory markers: interleukin-2, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 β (IL-1β), interferon-gamma, and tumor necrosis factor-α (TNF-α). Patients with NEC had much higher median preoperative levels of IL-6 (NEC: 8,381 pg/mL; SIP: 36 pg/mL; PDA: 25 pg/mL, p neonate. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. A case of pemphigus foliaceus and pustular psoriasis A case of pemphigus foliaceus and pustular psoriasis with a brief review of literature

    Directory of Open Access Journals (Sweden)

    Darjani Abbas

    2017-10-01

    Full Text Available Rarely pemphigus foliaceus could be associated with generalized pustular psoriasis. A 66-year-old woman with diffuse flaccid bullae and erosions of pemphigus foliaceus underwent two sessions of pulse therapy of corticosteroid and oral prednisolone during the interval time. Two weeks after the second session of pulse therapy with improvement of the lesions, during tapered dosage of oral prednisolone, facial annular erythematous lesions appeared and were superimposed by generalized pustular eruptions. Skin biopsy of pustular lesions showed pustular psoriasis so intramuscular methotrexate was added. Two years later, during decreasing dosage of methotrexate and prednisolone, she had eruptive recurrence of pustules and flaccid bullae associated with erythroderma and fever which were controlled with increasing dosage of corticosteroid and starting oral retinoid. These hypotheses may explain co-occurring pemphigus foliaceus and pustular psoriasis: decreasing dosage of corticosteroid, interleukin-8 overproduction in keratinocytes and increased activity of plasminogen activator in skin lesions.

  15. The influence of inflammation and hematocrit on clot strength in canine thromboelastographic hypercoagulability

    DEFF Research Database (Denmark)

    Marschner, Clara B.; Wiinberg, Bo; Tarnow, Inge

    2018-01-01

    count, and hematocrit were measured using CBC, TEG, platelet aggregation on multiplate, platelet activity on flow cytometry, and hemostatic and inflammatory markers on plasma and serum analyses. ANOVA and multilinear regression analyses indicated that especially hematocrit and the inflammatory...... parameters C-reactive protein and interleukin-8 showed best association with overall clot strength in diseased dogs with hypercoagulable TEG tracings. Ratios presumed to reflect platelet contribution to the TEG tracing obtained in TEG analyses with Cyt D were related especially with hematocrit and P......-selectin expression of platelets measured after γ-Thrombin activation on flow cytometry. Conclusion: Overall clot strength in TEG analyses of the hypercoagulable dogs included in the present study appears to be primarily associated with inflammation as well as hematocrit. Furthermore, the ratio between standard TEG...

  16. Dietary administration of microalgae Navicula sp. affects immune status and gene expression of gilthead seabream (Sparus aurata).

    Science.gov (United States)

    Reyes-Becerril, Martha; Guardiola, Francisco; Rojas, Maurilia; Ascencio-Valle, Felipe; Esteban, María Ángeles

    2013-09-01

    Effects of silage microalgae enriched with a probiotic and lyophilized microalgae were evaluated on main immune parameters and different gene expression of gilthead seabream (Sparus aurata L.). A total of 60 seabream were grouped into 3 treatment diets which were a control diet (commercial diet) without microalgae (C), commercial diet supplemented with silage microalgae Navicula sp. plus Lactobacillus sakei 5-4 (10(6) CFU g(-1)) (SM), and commercial diet supplemented with lyophilized microalgae (LM) for 4 weeks. Generally, the results showed a significant increase in the immune parameters, principally in leucocyte peroxidase, phagocytosis and complement activities in fish fed with SM diet compared to control group. About the gene expression in head-kidney, transcript levels (Interleukin-8, Interleukin-1β and β-defensin) were upregulated in fish fed with SM after 4 weeks of treatments. However, the gene expression was upregulated in intestine from fish fed with LM with significant difference in transferrin and cyclooxygenase 2 gene at 2 weeks, and in occludin, transferrin, interleukin-8 and interleukin-1β at 4 weeks. Finally, about the digestive enzymes, LM diet caused an upregulated of α-amylase and alkaline phosphatase genes at 2 weeks; however SM diet caused an upregulated trypsin gene at 4 weeks. SM diet a higher enhancing effect on gilthead seabream immune parameters than that observed when using LM. Furthermore, dietary administration of microalgae Navicula sp. provokes upregulation of several genes in the gut that correlates with slight inflammation. Further studies are needed to know if this diatom could be useful for administering as diet supplement for farmed fish. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Invasive Streptococcus mutans induces inflammatory cytokine production in human aortic endothelial cells via regulation of intracellular toll-like receptor 2 and nucleotide-binding oligomerization domain 2.

    Science.gov (United States)

    Nagata, E; Oho, T

    2017-04-01

    Streptococcus mutans, the primary etiologic agent of dental caries, can gain access to the bloodstream and has been associated with cardiovascular disease. However, the roles of S. mutans in inflammation in cardiovascular disease remain unclear. The aim of this study was to examine cytokine production induced by S. mutans in human aortic endothelial cells (HAECs) and to evaluate the participation of toll-like receptors (TLRs) and cytoplasmic nucleotide-binding oligomerization domain (NOD) -like receptors in HAECs. Cytokine production by HAECs was determined using enzyme-linked immunosorbent assays, and the expression of TLRs and NOD-like receptors was evaluated by real-time polymerase chain reaction, flow cytometry and immunocytochemistry. The involvement of TLR2 and NOD2 in cytokine production by invaded HAECs was examined using RNA interference. The invasion efficiencies of S. mutans strains were evaluated by means of antibiotic protection assays. Five of six strains of S. mutans of various serotypes induced interleukin-6, interleukin-8 and monocyte chemoattractant protein-1 production by HAECs. All S. mutans strains upregulated TLR2 and NOD2 mRNA levels in HAECs. Streptococcus mutans Xc upregulated the intracellular TLR2 and NOD2 protein levels in HAECs. Silencing of the TLR2 and NOD2 genes in HAECs invaded by S. mutans Xc led to a reduction in interleukin-6, interleukin-8 and monocyte chemoattractant protein-1 production. Cytokine production induced by invasive S. mutans via intracellular TLR2 and NOD2 in HAECs may be associated with inflammation in cardiovascular disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Basal level and behaviour of cytokines in a randomized outpatient trial comparing chemotherapy and biochemotherapy in metastatic melanoma.

    Science.gov (United States)

    Guida, Michele; Riccobon, Angela; Biasco, Guido; Ravaioli, Alessandra; Casamassima, Addolorata; Freschi, Andrea; Palma, Maurizio Dalla; Galligioni, Enzo; Nortilli, Rolando; Chiarion-Sileni, Vanna; Picozzo, Jacopo; Romanini, Antonella; Nanni, Oriana; Ridolfi, Ruggero

    2006-08-01

    Cytokines play a crucial role in the host's immune response. In melanoma patients, cytokine profiles seems to be related to the clinical course and their imbalance could be associated to tumour progression. Thus, we studied a panel of baseline cytokines and their behaviour during treatment in order to verify their correlation with clinical outcomes. Interleukin-6, interleukin-8, interleukin-10, interleukin-12 and soluble receptor of interleukin-2 were evaluated in 90 out of 176 metastatic melanoma patients enrolled in a phase III study comparing chemotherapy and biochemotherapy. We divided patients into three different groups according to their own cytokine levels (low, intermediate and high) and then we correlated these groups with some clinical features. We also monitored the cytokines during the treatment in a subgroup of 37 patients. In univariate analysis, higher values of interleukin-6 (P = 0.005), soluble receptor of interleukin-2 (P = 0.001) and interleukin-12 (P = 0.010) were correlated with a worse survival. Conversely, interleukin-8 was unable to discriminate patients with different prognoses, and interleukin-10 was undetectable in the majority of patients. In multivariate analysis, only soluble receptor of interleukin-2 maintained its independent role in survival. The impact of baseline cytokines on response was insignificant. Regarding the behaviours of cytokines during treatment, the most remarkable aspect was a progressive increase of interleukin-12 and soluble receptor of interleukin-2 in patients with a better survival. In our metastatic melanoma patients, higher basal levels of interleukin-6, interleukin-12 and soluble receptor of interleukin-2 were associated with a worse survival. In contrast, a progressive increase of interleukin-12 and soluble receptor of interleukin-2 was observed during treatment in patients with a better survival.

  19. Spontaneous breathing with biphasic positive airway pressure attenuates lung injury in hydrochloric acid-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Xia, Jingen; Zhang, Heng; Sun, Bing; Yang, Rui; He, Hangyong; Zhan, Qingyuan

    2014-06-01

    It has been proved that spontaneous breathing (SB) with biphasic positive airway pressure (BIPAP) can improve lung aeration in acute respiratory distress syndrome compared with controlled mechanical ventilation. The authors hypothesized that SB with BIPAP would attenuate lung injury in acute respiratory distress syndrome compared with pressure-controlled ventilation. Twenty male New Zealand white rabbits with hydrochloric acid aspiration-induced acute respiratory distress syndrome were randomly ventilated using the BIPAP either with SB (BIPAP plus SB group) or without SB (BIPAP minus SB group) for 5 h. Inspiration pressure was adjusted to maintain the tidal volume at 6 ml/kg. Both groups received the same positive end-expiratory pressure level at 5 cm H2O for hemodynamic goals. Eight healthy animals without ventilatory support served as the control group. The BIPAP plus SB group presented a lower ratio of dead space ventilation to tidal volume, a lower respiratory rate, and lower minute ventilation. No significant difference in the protein levels of interleukin-6 and interleukin-8 in plasma, bronchoalveolar lavage fluid, and lung tissue were measured between the two experimental groups. However, SB resulted in lower messenger ribonucleic acid levels of interleukin-6 (mean ± SD; 1.8 ± 0.7 vs. 2.6 ± 0.5; P = 0.008) and interleukin-8 (2.2 ± 0.5 vs. 2.9 ± 0.6; P = 0.014) in lung tissues. In addition, lung histopathology revealed less injury in the BIPAP plus SB group (lung injury score, 13.8 ± 4.6 vs. 21.8 ± 5.7; P hydrochloric acid-induced acute respiratory distress syndrome, SB with BIPAP attenuated lung injury and improved respiratory function compared with controlled ventilation with low tidal volume.

  20. Impact of heavy smoking on the clinical, microbiological and immunological parameters of patients with dental implants: a prospective cross-sectional study.

    Science.gov (United States)

    Ata-Ali, Javier; Flichy-Fernández, Antonio Juan; Alegre-Domingo, Teresa; Ata-Ali, Fadi; Peñarrocha-Diago, Miguel

    2016-11-01

    The aim of the present study was to investigate how heavy smoking influences the clinical, microbiological, and host-response characteristics in peri-implant sulcus fluid of patients with healthy dental implants. A total of 29 individuals with 74 dental implants were included in the present study; 20 implants were in heavy smokers and 54 were in non-smokers. The modified gingival index, modified plaque index, and probing pocket depth were evaluated. Periodontopathogenic bacteria Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis were evaluated, together with the total bacterial load. Peri-implant sulcus fluid samples were analyzed for the quantification of interleukin-8, interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α. No significant differences in the clinical parameters evaluated were found between the groups, although smokers had poorer peri-implant parameters. Among the smokers, subgingival microbiota was composed of a greater number of periodontal pathogens; these differences were not statistically significant. Smokers showed a greater expression of interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α, but interleukin-8 was slightly higher among non-smokers, but not significantly. Although smokers presented deeper probing depths, bleeding on probing, and peri-implant microbiota composed of a greater number of periodontal pathogens than in non-smoking patients, these data did not show significant differences. In the present study, and in relation to the samples analyzed, smoking alone did not influence the immunological and microbiological parameters in dental implants with healthy peri-implant tissues. Further studies with larger samples are required to better evaluate the influence of smoking on dental implants. © 2015 Wiley Publishing Asia Pty Ltd.

  1. Impact of the Levonorgestrel-Releasing Intrauterine System on the Progression of Chlamydia trachomatis Infection to Pelvic Inflammatory Disease in a Baboon Model.

    Science.gov (United States)

    Eastman, Alison J; Bergin, Ingrid L; Chai, Daniel; Bassis, Christine M; LeBar, William; Oluoch, George O; Liechty, Emma R; Nyachieo, Atunga; Young, Vincent B; Aronoff, David M; Patton, Dorothy L; Bell, Jason D

    2018-01-30

    Understanding the relationship between the levonorgestrel (LNG)-releasing intrauterine system (IUS) and sexually transmitted infections (STIs) is increasingly important as use of the LNG-IUS grows to include women at higher risk for STIs. This study assessed the impact of the LNG-IUS on development of Chlamydia trachomatis pelvic inflammatory disease, using a baboon model. Baboons with and those without the LNG-IUS were cervically inoculated with C. trachomatis and monitored daily, and cervical and fallopian tube swab specimens were collected weekly for C. trachomatis quantitation by nucleic acid amplification testing and culture. Vaginal swab specimens were collected for cytokine analysis, and serum samples were obtained for detection of C. trachomatis antibodies. The LNG-IUS resulted in an increased C. trachomatis burden in the cervix, with the bacterial burden in the LNG-IUS group diverging from that in the non-LNG-IUS group by 6 weeks after infection. One of 7 baboons in the non-LNG-IUS group and 2 of 6 in the LNG-IUS group developed pelvic inflammatory disease, while 3 animals in each group met criteria suggestive of pelvic inflammatory disease. LNG-IUS increased baseline interleukin 8 levels but failed to further upregulate interleukin 8 during infection. In LNG-IUS recipients, early perturbations in the interleukin 1β axis corresponded to decreased C. trachomatis clearance and increased T-helper type 2 immune responses. LNG-IUS use results in delayed clearance of C. trachomatis and might alter the reproductive tract immune environment. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  2. Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner.

    Science.gov (United States)

    Doerflinger, Sylvie Y; Throop, Andrea L; Herbst-Kralovetz, Melissa M

    2014-06-15

    Bacterial vaginosis increases the susceptibility to sexually transmitted infections and negatively affects women's reproductive health. To investigate host-vaginal microbiota interactions and the impact on immune barrier function, we colonized 3-dimensional (3-D) human vaginal epithelial cells with 2 predominant species of vaginal microbiota (Lactobacillus iners and Lactobacillus crispatus) or 2 prevalent bacteria associated with bacterial vaginosis (Atopobium vaginae and Prevotella bivia). Colonization of 3-D vaginal epithelial cell aggregates with vaginal microbiota was observed with direct attachment to host cell surface with no cytotoxicity. A. vaginae infection yielded increased expression membrane-associated mucins and evoked a robust proinflammatory, immune response in 3-D vaginal epithelial cells (ie, expression of CCL20, hBD-2, interleukin 1β, interleukin 6, interleukin 8, and tumor necrosis factor α) that can negatively affect barrier function. However, P. bivia and L. crispatus did not significantly upregulate pattern-recognition receptor-signaling, mucin expression, antimicrobial peptides/defensins, or proinflammatory cytokines in 3-D vaginal epithelial cell aggregates. Notably, L. iners induced pattern-recognition receptor-signaling activity, but no change was observed in mucin expression or secretion of interleukin 6 and interleukin 8. We identified unique species-specific immune signatures from vaginal epithelial cells elicited by colonization with commensal and bacterial vaginosis-associated bacteria. A. vaginae elicited a signature that is consistent with significant disruption of immune barrier properties, potentially resulting in enhanced susceptibility to sexually transmitted infections during bacterial vaginosis. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Randomized trial of non-invasive ventilation combined with exercise training in patients with chronic hypercapnic failure due to chronic obstructive pulmonary disease.

    Science.gov (United States)

    Márquez-Martín, Eduardo; Ruiz, Francisco Ortega; Ramos, Pilar Cejudo; López-Campos, Jose Luis; Azcona, Borja Valencia; Cortés, Emilia Barrot

    2014-12-01

    Non-invasive ventilation and exercise training might prove beneficial in the management of COPD patients. to compare the combined use of exercise training and non-invasive ventilation with the two interventions separately in chronic respiratory failure due to chronic obstructive pulmonary disease. As primary objective exercise capacity and secondary objectives gas exchange, peripheral muscle strength, BODE index, quality of life and systemic inflammatory response. Forty-five patients with severe chronic obstructive pulmonary disease were randomized into three groups for an intervention of 12 weeks: exercise training alone, ventilation alone and combined treatment. We assessed exercise capacity, pulmonary function, BODE index, perception of dyspnoea, quality of life and several biomarkers. All exercise capacity parameters improved after training and the combined treatment. In addition, peripheral muscle strength and six-minute walk distance increased after ventilation. We found differences between the combined group and the ventilation group in submaximal effort and in oxygen consumption. Changes in respiratory function were observed in blood gases that improved after ventilation and the combined treatment, with differences between these groups. BODE index, perception of dyspnoea and quality of life improved in all three groups without differences between groups. Levels of interleukin 8 and tumour necrosis factor α decreased after ventilation, and interleukin 8, C-reactive protein and surfactant protein D decreased after training, while all four of these markers fell after the combined treatment. No differences between groups were found. The combination of ventilation and exercise training had greater benefits than the separate treatments: improvements were observed in both blood gases and the levels of more biomarkers decreased. In addition, submaximal exercise capacity increased in all groups. The improvements seen in BODE index, perception of dyspnoea and

  4. Annexin A2 in amniotic fluid: correlation with histological chorioamnionitis, preterm premature rupture of membranes, and subsequent preterm delivery.

    Science.gov (United States)

    Namba, Fumihiko; Ina, Shihomi; Kitajima, Hiroyuki; Yoshio, Hiroyuki; Mimura, Kazuya; Saito, Shigeru; Yanagihara, Itaru

    2012-01-01

    The aim of this study was to determine whether amniotic fluid levels of annexin A2, a phospholipid-binding protein that is abundant in amnion and regulates fibrin homeostasis, are associated with histological chorioamnionitis, preterm premature rupture of the membranes, and subsequent preterm delivery. Amniotic fluid was obtained from 55 pregnant women with preterm labor and/or preterm premature rupture of the membranes before 32weeks of gestation, and amniotic fluid levels of annexin A2 were measured with a sandwich enzyme-linked immunosorbent assay. Amniotic fluid levels of annexin A2 in patients with histological chorioamnionitis was higher than that in the remainder (P=0.053), whereas amniotic fluid levels of annexin A2 in patients with preterm premature rupture of the membranes was significantly higher than that in the remainder (P=0.002). Amniotic levels of annexin A2 was a fair test (area under receiver-operator characteristic curve=0.679), and amniotic fluid levels of annexin A2>878.2ng/mL had a sensitivity of 68.8%, a specificity of 65.2%, a positive predictive value of 73.3%, and a negative predictive value of 60.0% for predicting delivery within 2weeks after amniotic fluid sampling. Furthermore, the combined use of amniotic fluid cut-off levels of 878.2ng/mL for annexin A2 and 13.3ng/mL for interleukin-8 improved the specificity (91.3%) and the positive predictive value (89.5%). We identified amniotic fluid levels of annexin A2, especially in combination with amniotic fluid levels of interleukin-8, as a novel predictive marker for preterm delivery. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

  5. Prophylactic peritoneal dialysis following cardiopulmonary bypass in children is associated with decreased inflammation and improved clinical outcomes.

    Science.gov (United States)

    Sasser, William C; Dabal, Robert J; Askenazi, David J; Borasino, Santiago; Moellinger, Ashley B; Kirklin, James K; Alten, Jeffrey A

    2014-01-01

    To investigate impact of prophylactic peritoneal dialysis (PD) on clinical outcomes and inflammatory cytokines in children following cardiac surgery with cardiopulmonary bypass. Prospective before-and-after nonrandomized cohort study. Pediatric cardiovascular intensive care unit in tertiary hospital. Fifty-two consecutive neonates and infants at high risk for postoperative fluid overload following cardiopulmonary bypass. All had PD catheters placed during primary cardiac surgery. Initial 27 patients were managed with passive peritoneal drainage and diuretics (controls). Following 25 patients were started on prophylactic PD in immediate postoperative period and managed per PD protocol (+PD). Cumulative fluid balance, indices of disease severity, and clinical outcomes were prospectively collected. Plasma interleukin-6 and interleukin-8 were measured immediately before-and-after cardiopulmonary bypass and at 24 and 48 hours post-cardiopulmonary bypass. Demographics, diagnoses, and intraoperative variables were similar. Median net fluid balance was more negative in +PD at 24 hours, -24 mL/kg (interquartile range: -62, 11) vs. +18 mL/kg (interquartile range: -26, 11), P = .003, and 48 hours, -88 mL/kg (interquartile range: -132, -54) vs. -46 mL/kg (interquartile range: -84, -12), P = .004. +PD had median 55 mL/kg less fluid intake at 24 hours, P = .058. Peritoneal drain, urine, and chest tube output were comparable over first 24 hours. Mean inotrope score was lower in +PD at 24 hours. +PD had earlier sternal closure--24 hours (interquartile range: 20, 40) vs. 63 hours (interquartile range: 44, 72), P interquartile range: 49, 135) vs. 125 hours (interquartile range: 70, 195), P = .10. +PD experienced lower serum concentrations of interleukin-6 and interleukin-8 at 24 hours. Prophylactic PD is associated with greater net negative fluid balance, decreased inotrope requirements, and lower serum concentrations of inflammatory cytokines in the early postoperative

  6. The effect of metal ions released from different dental implant-abutment couples on osteoblast function and secretion of bone resorbing mediators.

    Science.gov (United States)

    Alrabeah, Ghada O; Brett, Peter; Knowles, Jonathan C; Petridis, Haralampos

    2017-11-01

    The etiology of the reduced marginal bone loss observed around platform-switched implant-abutment connections is not clear but could be related to the release of variable amounts of corrosion products. The present study evaluated the effect of different concentrations of metal ions released from different implant abutment couples on osteoblastic cell viability, apoptosis and expression of genes related to bone resorption. Osteoblastic cells were exposed to five conditions of culture media prepared containing metal ions (titanium, aluminum, vanadium, cobalt, chromium and molybdenum) in different concentrations representing the amounts released from platform-matched and platform-switched implant-abutment couples as a result of an earlier accelerated corrosion experiment. Cell viability was evaluated over 21days using the Alamar Blue assay. Induction of apoptosis was measured after 24h of exposure using flow cytometry. Expression of interleukin-6, interleukin-8, cyclooxygenase-2, caspase-8, osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (RANKL) by osteoblastic cells were analysed after exposure for 1, 3 and 21days using real-time quantitative polymerase chain reaction assay RESULTS: Metal ions in concentrations representing the platform-matched groups led to a reduction in cell viability (PMetal ions up-regulated the expression of interleukin-6, interleukin-8, cyclooxygenase-2 and RANKL in a dose dependent manner after 1day of exposure (Pmetal ions. The change in cytokine levels expressed was directly proportional to the metal ion concentration. The observed biological responses to decreased amounts of metal ions released from platform-switched implant-abutment couples compared to platform-matched couples may partly explain the positive radiographic findings in respect to crestal bone level when utilising the "platform-switching" concept, which highlights the possible role of corrosion products in the mediation of crestal bone loss around

  7. Cholecystokinin-stimulated monocytes produce inflammatory cytokines and eicosanoids.

    Science.gov (United States)

    Cunningham, M E; Shaw-Stiffel, T A; Bernstein, L H; Tinghitella, T J; Claus, R E; Brogan, D A; McMillen, M A

    1995-04-01

    Plasma cholecystokinin increases with enteral feeding. Cholecystokinin increases intracellular calcium in lymphocytes/monocytes and is a lymphocyte co-mitogen. We hypothesize that decreased cholecystokinin production with "bowel rest" and parenteral nutrition may be beneficial in inflammatory bowel disease by down-regulating gut immune/inflammatory mechanisms. The majority of cells observed in mucosa of inflammatory bowel disease are monocytes and neutrophils. Cholecystokinin effect was therefore measured on monocyte production of proinflammatory mediators (tumor necrosis factor alpha, interleukin-1 beta, interleukin-6) and neutrophil chemotaxins/activators (interleukin-8, granulocyte-macrophage colony stimulating factor, and leukotriene B4). Peripheral blood monocytes (0.5 x 10(6)) from healthy donors in 1 mL of RPMI 1640 plus 5% fetal calf serum were cultured for 24 h in 5% CO2 at 37 degrees C with 5 micrograms/mL endotoxin, 1 x 10(-7) M cholecystokinin, or no agonist. Supernatants were analyzed by ELISA for cytokines and leukotriene B4. Endotoxin-stimulated monocytes produced 1130 pg/mL tumor necrosis factor versus 81 pg/mL for cholecystokinin, 612 pg/mL interleukin-1 versus 10 pg/mL, 694 pg/mL interleukin-6 versus 30 pg/mL, 4531 pg/mL of interleukin-8 versus 3848 pg/mL, 21 pg/mL granulocyte-macrophage colony stimulating factor versus 9 pg/mL, and 21 pg/mL leukotriene B4 versus 12 pg/mL. Controls produced no cytokines/eicosanoids (N = 8, p alimentation may decrease inflammatory mediator production.

  8. Fermented whey-based product improves the quality of life of males with moderate lower urinary tract symptoms: A randomized double-blind study.

    Science.gov (United States)

    Ausmees, Kristo; Ehrlich-Peets, Kersti; Vallas, Mirjam; Veskioja, Andre; Rammul, Kadi; Rehema, Aune; Zilmer, Mihkel; Songisepp, Epp; Kullisaar, Tiiu

    2018-01-01

    The purpose of this research was to evaluate the effect of a specific fermented whey product on lower urinary tract symptoms, main prostate related indices and oxidative stress/inflammatory markers in urine and seminal plasma in men with moderate dysuric symptoms. An additional purpose was to clarify associations between different parameters with special emphasis on pain. This was a prospective randomized double-blind 4-weeks study on men with moderate lower urinary tract symptoms who underwent the evaluation for quality of life at the baseline and at the end of the study. The symptoms were characterized by International Prostate Symptom Score (I-PSS) and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-PSI), the maximum urinary flow and the main prostate-related indices. In order to obtain more comprehensive information about the effects of fermented whey product on systemic oxidative stress marker 8-EPI and seminal plasma inflammatory markers (interleukin-6 and interleukin-8) were also measured. After 4 weeks consumption of fermented whey product there was a statistically significant decrease of prostate-specific antigen level in serum and systemic stress marker 8-EPI in urine compared to control group. Maximum urinary flow and NIH-PSI all studied scores and sub-scores had also significant improvement. In addition, seminal plasma interleukin-8 level substantially decreased. The consumption of special fermented whey product improved urinary function, reduced lower urinary tract symptoms, systemic oxidative stress marker and seminal plasma inflammatory status. Thus it contributed to an improvement of the quality of life in men with moderate lower urinary tract symptoms.

  9. Phytochemical and anti-inflammatory activities of aqueous leaf extract of Indian borage (oregano) on rats induced with inflammation.

    Science.gov (United States)

    Akinbo, David Bolaji; Onyeaghala, Augustine A; Emomidue, Jennifer Ochuko; Ogbhemhe, Stephanie Okhuriafe; Okpoli, Henry Chijindu

    2018-03-30

    The Indian borage (Plectranthus amboinicus) also called Oregano contains many effective antioxidants, which includes caffeic acid, rosmarinic acid and flavonoids. It has been employed in traditional medicine for its several health benefits including the prevention and cure of many debilitating diseases. Anti-inflammatory properties of Plectranthus amboinicus grown within this environment have not been adequately explored. The protective and therapeutic effects of Oregano against endotoxaemia and inflammation were evaluated using lipopolysaccharide (LPS)-induced rat models. A total of 30 Wistar rats were randomly selected for this study and divided into six groups, with each group having 5 rats. Inflammation was induced on appropriate animal groups using LPS injection at a concentration of 4 mg/kg. Aqueous leaf extract of Indian borage was administered orally in four doses (100 mg/kg, 200 mg/kg, 400 mg/kg post-LPS exposure and 150 mg/kg pre-LPS exposure) to respective treatment rat groups. Haematological profile, toxicity profile of liver and kidney and levels of biomarkers of inflammation were assayed using standard methods. Rats injected with LPS showed severe anaemia and marked leucopoenia with significant decrease in monocytes compared to the control group (p< 0.05). There was increased expression of interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) (p< 0.05) in the peripheral circulation of rats exposed to LPS. Treatment with Indian borage significantly (p< 0.05) reduced the toxic effects in the LPS-treated animals and attenuated the increase in the expression of circulating proinflammatory cytokines; tumor necrosis factor alpha (TN-Fα) and interleukin-8 (IL-8) caused by LPS. Indian borage pretreatment also significantly (p< 0.05) counteracted the associated haematological dyscrasias caused by exposure to LPS. The extract elicited a significant protective effect on the kidney and liver as evidenced by the decreased renal markers and hepatic enzyme

  10. Inflammatory and Oxidative Responses Induced by Exposure to Commonly Used e-Cigarette Flavoring Chemicals and Flavored e-Liquids without Nicotine

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    Thivanka Muthumalage

    2018-01-01

    Full Text Available Background: The respiratory health effects of inhalation exposure to e-cigarette flavoring chemicals are not well understood. We focused our study on the immuno-toxicological and the oxidative stress effects by these e-cigarette flavoring chemicals on two types of human monocytic cell lines, Mono Mac 6 (MM6 and U937. The potential to cause oxidative stress by these flavoring chemicals was assessed by measuring the production of reactive oxygen species (ROS. We hypothesized that the flavoring chemicals used in e-juices/e-liquids induce an inflammatory response, cellular toxicity, and ROS production.Methods: Two monocytic cell types, MM6 and U937 were exposed to commonly used e-cigarette flavoring chemicals; diacetyl, cinnamaldehyde, acetoin, pentanedione, o-vanillin, maltol and coumarin at different doses between 10 and 1,000 μM. Cell viability and the concentrations of the secreted inflammatory cytokine interleukin 8 (IL-8 were measured in the conditioned media. Cell-free ROS produced by these commonly used flavoring chemicals were also measured using a 2′,7′dichlorofluorescein diacetate probe. These DCF fluorescence data were expressed as hydrogen peroxide (H2O2 equivalents. Cytotoxicity due to the exposure to selected e-liquids was assessed by cell viability and the IL-8 inflammatory cytokine response in the conditioned media.Results: Treatment of the cells with flavoring chemicals and flavored e-liquid without nicotine caused cytotoxicity dose-dependently. The exposed monocytic cells secreted interleukin 8 (IL-8 chemokine in a dose-dependent manner compared to the unexposed cell groups depicting a biologically significant inflammatory response. The measurement of cell-free ROS by the flavoring chemicals and e-liquids showed significantly increased levels of H2O2 equivalents in a dose-dependent manner compared to the control reagents. Mixing a variety of flavors resulted in greater cytotoxicity and cell-free ROS levels compared to the

  11. Combination of new multifunctional molecules for erythematotelangiectatic rosacea disorder

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    Chajra H

    2015-10-01

    Full Text Available Hanane Chajra,1 Mahdi Nadim,2 Daniel Auriol,3 Kuno Schweikert,1 Fabrice Lefevre1 1Induchem AG, Volkestwil, Switzerland; 2CBM-CNRS, Orléans Cedex, 3Libragen SA, Toulouse, France Background: Rosacea, a common chronic skin disorder, is currently managed by patient education, pharmacological drugs, medical devices (laser and light therapies, and use of proper skin cares. Unfortunately, none of these actual treatments used alone or in combination is curative, and so we proposed a dermocosmetic active ingredient to mitigate some aspects of the rosacea and particularly for erythematotelangiectatic rosacea. Methods: Dermocosmetic active ingredient is composed of three glucosylated derivatives of natural plants hydroxybenzoic acid and hydroxycinnamic acids (rosmarinic acid, gallic acid, and caffeic acid. Anti-inflammatory, anti-angiogenesis, and anti-degranulation studies were done on cellular models (keratinocytes, mast cells, and endothelial cells. Efficiency of the active ingredient in comparison to placebo was assessed clinically on human volunteers having erythematotelangiectatic rosacea. The active and placebo were applied topically twice a day for 28 days. Biometrical analyses were done using a siascope tool. Results: We found that the active ingredient decreases inflammation (inhibition of interleukin-8 and tumor necrosis factor release, decreases degranulation of mast cells (inhibition of histamine release, and controls angiogenesis mechanism (inhibition of the production of vascular endothelial growth factor and neovessel formation on cellular models. Study on human volunteers confirmed macroscopically the efficiency of this active ingredient, as we observed no neovessel formation and less visible vessels. Conclusion: Although rosacea is a skin condition disorder that is difficult to heal, the studies have shown that this active ingredient could be a dermocosmetic support, especially for erythematotelangiectatic rosacea armamentarium. The

  12. Milnacipran treatment and potential biomarkers in depressed patients following an initial SSRI treatment failure: a prospective, open-label, 24-week study

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    Hashimoto T

    2015-12-01

    Full Text Available Tasuku Hashimoto,1,2 Daiji Sakurai,1 Yasunori Oda,1 Tadashi Hasegawa,3 Nobuhisa Kanahara,4 Tsuyoshi Sasaki,3 Hideki Komatsu,3,5 Junpei Takahashi,1,5 Takahiro Oiwa,6 Yoshimoto Sekine,4,5 Hiroyuki Watanabe,1 Masaomi Iyo1,3 1Department of Psychiatry, Chiba University Graduate School of Medicine, 2Sodegaura Satsukidai Hospital, 3Department of Psychiatry, Chiba University Hospital, 4Division of Medical Treatment and Rehabilitation, Centre for Forensic Mental Health, Chiba University, 5Choshi Kokoro Clinic, 6Mobara Shinkeika Hospital, Chiba, Japan Background: We assessed the effect of switching patients with major depressive disorder to milnacipran following an initial selective serotonin reuptake inhibitor treatment failure, and explored potential biomarkers in their blood.Methods: We conducted a prospective, open-label, 24-week trial. Depression was assessed with the 17-item Hamilton Depression Rating Scale. Patients showing a ≥50% reduction in Hamilton Depression Rating Scale scores from baseline to final visit were considered responders. Regarding adverse effects (AEs, moderate-to-severe AEs were specifically identified as effects that required any medical treatment or that induced treatment withdrawals. We also measured blood levels of various molecules including inflammatory cytokines.Results: Of the 30 participants who enrolled, 17 completed this study. The responder rate was 30% (n=10. Baseline serum levels of interleukin-6 (Z=-2.155; P=0.031 and interleukin-8 (Z=-2.616; P=0.009 were significantly higher when moderate-to-severe AEs were present (n=13 patients with moderate-to-severe AEs. Serum levels of macrophage inflammatory protein-1β showed a significant continuous decrease from the baseline level (Friedman’s test: χ2=23.9, df=4, P<0.001 only in non-responders.Conclusion: These results demonstrate that serum levels of interleukin-6, interleukin-8, and macrophage inflammatory protein-1β as potential blood biomarkers could be utilized

  13. Biodegradable cationic polymeric nanocapsules for overcoming multidrug resistance and enabling drug-gene co-delivery to cancer cells

    Science.gov (United States)

    Chen, Chih-Kuang; Law, Wing-Cheung; Aalinkeel, Ravikumar; Yu, Yun; Nair, Bindukumar; Wu, Jincheng; Mahajan, Supriya; Reynolds, Jessica L.; Li, Yukun; Lai, Cheng Kee; Tzanakakis, Emmanuel S.; Schwartz, Stanley A.; Prasad, Paras N.; Cheng, Chong

    2014-01-01

    Having unique architectural features, cationic polymeric nanocapsules (NCs) with well-defined covalently stabilized biodegradable structures were generated as potentially universal and safe therapeutic nanocarriers. These NCs were synthesized from allyl-functionalized cationic polylactide (CPLA) by highly efficient UV-induced thiol-ene interfacial cross-linking in transparent miniemulsions. With tunable nanoscopic sizes, negligible cytotoxicity and remarkable degradability, they are able to encapsulate doxorubicin (Dox) with inner cavities and bind interleukin-8 (IL-8) small interfering RNA (siRNA) with cationic shells. The Dox-encapsulated NCs can effectively bypass the P-glycoprotein (Pgp)-mediated multidrug resistance of MCF7/ADR cancer cells, thereby resulting in increased intracellular drug concentration and reduced cell viability. In vitro studies also showed that the NCs loaded with Dox, IL-8 siRNA and both agents can be readily taken up by PC3 prostate cancer cells, resulting in a significant chemotherapeutic effect and/or IL-8 gene silencing.Having unique architectural features, cationic polymeric nanocapsules (NCs) with well-defined covalently stabilized biodegradable structures were generated as potentially universal and safe therapeutic nanocarriers. These NCs were synthesized from allyl-functionalized cationic polylactide (CPLA) by highly efficient UV-induced thiol-ene interfacial cross-linking in transparent miniemulsions. With tunable nanoscopic sizes, negligible cytotoxicity and remarkable degradability, they are able to encapsulate doxorubicin (Dox) with inner cavities and bind interleukin-8 (IL-8) small interfering RNA (siRNA) with cationic shells. The Dox-encapsulated NCs can effectively bypass the P-glycoprotein (Pgp)-mediated multidrug resistance of MCF7/ADR cancer cells, thereby resulting in increased intracellular drug concentration and reduced cell viability. In vitro studies also showed that the NCs loaded with Dox, IL-8 siRNA and both

  14. Expression of blood serum proteins and lymphocyte differentiation clusters after chronic occupational exposure to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rybkina, Valentina L.; Azizova, Tamara V.; Adamova, Galina V.; Teplyakova, Olga V.; Osovets, Sergey V.; Bannikova, Maria V. [Southern Urals Biophysics Institute, Ozyorsk, Chelyabinsk Region (Russian Federation); Scherthan, Harry; Meineke, Viktor; Doerr, Harald [University of Ulm, Bundeswehr Institute of Radiobiology, Munich (Germany); Zurochka, Alexander V. [Immunology Institute, Yekaterinburg (Russian Federation)

    2014-11-15

    This study aimed to assess effects of chronic occupational exposure on immune status in Mayak workers chronically exposed to ionizing radiation (IR). The study cohort consists of 77 workers occupationally exposed to external gamma-rays at total dose from 0.5 to 3.0 Gy (14 individuals) and workers with combined exposure (external gamma-rays at total dose range 0.7-5.1 Gy and internal alpha-radiation from incorporated plutonium with a body burden of 0.3-16.4 kBq). The control group consists of 43 age- and sex-matched individuals who never were exposed to IR, never involved in any cleanup operations following radiation accidents and never resided at contaminated areas. Enzyme-linked immunoassay and flow cytometry were used to determine the relative concentration of lymphocytes and proteins. The concentrations of T-lymphocytes, interleukin-8 and immunoglobulins G were decreased in external gamma-exposed workers relative to control. Relative concentrations of NKT-lymphocytes, concentrations of transforming growth factor-β, interferon gamma, immunoglobulins A, immunoglobulins M and matrix proteinase-9 were higher in this group as compared with control. Relative concentrations of T-lymphocytes and concentration of interleukin-8 were decreased, while both the relative and absolute concentration of natural killers, concentration of immunoglobulins A and M and matrix proteinase-9 were increased in workers with combined exposure as compared to control. An inverse linear relation was revealed between absolute concentration of T-lymphocytes, relative and absolute concentration of T-helpers cells, concentration of interferon gamma and total absorbed dose from external gamma-rays in exposed workers. For workers with incorporated plutonium, there was an inverse linear relation of absolute concentration of T-helpers as well as direct linear relation of relative concentration of NKT-lymphocytes to total absorbed red bone marrow dose from internal alpha-radiation. In all, chronic

  15. Expression of blood serum proteins and lymphocyte differentiation clusters after chronic occupational exposure to ionizing radiation

    International Nuclear Information System (INIS)

    Rybkina, Valentina L.; Azizova, Tamara V.; Adamova, Galina V.; Teplyakova, Olga V.; Osovets, Sergey V.; Bannikova, Maria V.; Scherthan, Harry; Meineke, Viktor; Doerr, Harald; Zurochka, Alexander V.

    2014-01-01

    This study aimed to assess effects of chronic occupational exposure on immune status in Mayak workers chronically exposed to ionizing radiation (IR). The study cohort consists of 77 workers occupationally exposed to external gamma-rays at total dose from 0.5 to 3.0 Gy (14 individuals) and workers with combined exposure (external gamma-rays at total dose range 0.7-5.1 Gy and internal alpha-radiation from incorporated plutonium with a body burden of 0.3-16.4 kBq). The control group consists of 43 age- and sex-matched individuals who never were exposed to IR, never involved in any cleanup operations following radiation accidents and never resided at contaminated areas. Enzyme-linked immunoassay and flow cytometry were used to determine the relative concentration of lymphocytes and proteins. The concentrations of T-lymphocytes, interleukin-8 and immunoglobulins G were decreased in external gamma-exposed workers relative to control. Relative concentrations of NKT-lymphocytes, concentrations of transforming growth factor-β, interferon gamma, immunoglobulins A, immunoglobulins M and matrix proteinase-9 were higher in this group as compared with control. Relative concentrations of T-lymphocytes and concentration of interleukin-8 were decreased, while both the relative and absolute concentration of natural killers, concentration of immunoglobulins A and M and matrix proteinase-9 were increased in workers with combined exposure as compared to control. An inverse linear relation was revealed between absolute concentration of T-lymphocytes, relative and absolute concentration of T-helpers cells, concentration of interferon gamma and total absorbed dose from external gamma-rays in exposed workers. For workers with incorporated plutonium, there was an inverse linear relation of absolute concentration of T-helpers as well as direct linear relation of relative concentration of NKT-lymphocytes to total absorbed red bone marrow dose from internal alpha-radiation. In all, chronic

  16. Cervical cerclage placement decreases local levels of proinflammatory cytokines in patients with cervical insufficiency.

    Science.gov (United States)

    Monsanto, Stephany P; Daher, Silvia; Ono, Erika; Pendeloski, Karen Priscilla Tezotto; Trainá, Évelyn; Mattar, Rosiane; Tayade, Chandrakant

    2017-10-01

    Cervical insufficiency is characterized by premature, progressive dilation and shortening of the cervix during pregnancy. If left unattended, this can lead to the prolapse and rupture of the amniotic membrane, which usually results in midtrimester pregnancy loss or preterm birth. Previous studies have shown that proinflammatory cytokines such as interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor alpha are up-regulated in normal parturition but are also associated with preterm birth. Studies evaluating such markers in patients with cervical insufficiency have evaluated only their diagnostic potential. Even fewer studies have studied them within the context of cerclage surgery. The objective of the study was to evaluate the impact of local and systemic inflammatory markers on the pathogenesis of cervical insufficiency and the effect of cerclage surgery on the local immune microenvironment of women with cervical insufficiency. We recruited 28 pregnant women (12-20 weeks' gestation) diagnosed with insufficiency and referred for cerclage surgery and 19 gestational age-matched normal pregnant women as controls. Serum and cervicovaginal fluid samples were collected before and after cerclage surgery and during a routine checkup for normal women and analyzed using a targeted 13-plex proinflammatory cytokine assay. Before surgery, patients with cervical insufficiency had higher levels of interleukin-1β, interleukin-6, interleukin-12, monocyte chemoattractant protein-1 and tumor necrosis factor alpha in cervicovaginal fluid compared to controls, but after surgery, these differences disappeared. No differences were found in serum of insufficiency versus control women. In patients with insufficiency, the levels of interleukin-1β, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and interferon gamma in cervicovaginal fluid declined significantly after cerclage compared with before intervention, but these changes were not detected in serum

  17. Longitudinal Relationship of Low Leisure Satisfaction but not Depressive Symptoms With Systemic Low-Grade Inflammation in Dementia Caregivers

    Science.gov (United States)

    2014-01-01

    Objectives. This study aimed to further elucidate the biobehavioral mechanisms linking dementia caregiving with an increased cardiovascular disease risk. We hypothesized that both elevated depressive symptoms and a behavioral correlate of depression, low leisure satisfaction, are associated with systemic inflammation. Method. We studied 121 elderly Alzheimer’s disease caregivers who underwent 4 annual assessments for depressive symptoms, leisure satisfaction, and circulating levels of inflammatory markers. We used mixed-regression analyses controlling for sociodemographic and health-relevant covariates to examine longitudinal relationships between constructs of interest. Results. There were inverse relationships between total leisure satisfaction and tumor necrosis factor-α (TNF-α; p = .047), interleukin-8 (IL-8; p leisure activities was related to higher levels of TNF-α (p = .045), IL-8 (p leisure activities was related only to higher IL-8 levels (p = .023). Depressive symptoms were not associated with any inflammatory marker (all p values > .17). Depressive symptoms did not mediate the relationship between leisure satisfaction and inflammation. Discussion. Lower satisfaction with leisure activities is related to higher low-grade systemic inflammation. This knowledge may provide a promising way of improving cardiovascular health in dementia caregivers through behavioral activation treatments targeting low leisure satisfaction. PMID:23650246

  18. Possible role of central interleukins on the anorexigenic effect of lipopolysaccharide in chicks.

    Science.gov (United States)

    Tachibana, T; Kodama, T; Yamane, S; Makino, R; Khan, S I; Cline, M A

    2017-06-01

    1. The purpose of the present study was to determine if central interleukin-1β (IL1β), interleukin-6 (IL6) and interleukin-8 (IL8) affect feeding behaviour in chicks (Gallus gallus) and examine if central interleukins are related to the lipopolysaccharide (LPS)-induced anorexia. 2. Intra-abdominal (IA) injection of LPS significantly suppressed feeding behaviour and significantly increased mRNA expression of IL1β and IL8 in the diencephalon when compared to the control group, while IL6 tended to be increased. 3. Intracerebroventricular (ICV) injection of 200 ng IL1β significantly decreased food intake at 60 min after the injection while IL6 and IL8 had no effect. 4. IA injection of these ILs (200 ng) had no effect on food intake in chicks. 5. ICV injection of 200 ng IL1β did not affect water intake and plasma corticosterone concentration, suggesting that central IL1β might not be related to the regulation of drinking behaviour and the hypothalamus-pituitary-adrenal axis. 6. The present study demonstrated that central IL1β but not IL6 and IL8 might be related to the inhibition of feeding in chicks.

  19. Phytochemical Composition and Anti-Inflammatory Activity of Extracts from the Whole-Meal Flour of Italian Durum Wheat Cultivars

    Directory of Open Access Journals (Sweden)

    Barbara Laddomada

    2015-02-01

    Full Text Available In this study, the quali-quantitative composition of hydrophilic (phenolic acids and lipophilic (isoprenoids extracts from whole-meal flour of five elite Italian durum wheat cultivars was determined. Significant differences in the content of bioactive compounds were observed among the wheat extracts, in particular concerning the content of bound phenolic acids, lutein and β-tocotrienols. The cultivars Duilio and Svevo showed the highest amount of phenolic acids and isoprenoids, respectively. Extracts were evaluated for their anti-inflammatory activity on HT-29 human colon cells by measuring the levels of interleukin 8 (IL-8 and transforming growth factor β1 (TGF-β1. Durum wheat extracts significantly inhibited the secretion of the pro-inflammatory IL-8 mediator at 66 µg/mL of phenolic acids and at 0.2 µg/mL of isoprenoids. Conversely, the secretion of the anti-inflammatory mediator TGF-β1 was not modified by neither hydrophilic nor lipophilic extracts. These results provide further insight into the potential of durum wheat on human health suggesting the significance of varieties with elevated contents of bioactive components.

  20. The Kampo medicine Rokumigan possesses antibiofilm, anti-inflammatory, and wound healing properties.

    Science.gov (United States)

    Liao, James; Azelmat, Jabrane; Zhao, Lei; Yoshioka, Masami; Hinode, Daisuke; Grenier, Daniel

    2014-01-01

    Periodontal diseases, which are inflammatory diseases of bacterial origin affecting the tooth-supporting tissues, are characterized by inflammation and destruction of gingival connective tissue and alveolar bone, and may lead to tooth loss. The aim of the study was to investigate Rokumigan, a Kampo Japanese traditional medicine made of six different plants, for its capacity to prevent biofilm formation by Fusobacterium nucleatum, to inhibit interleukin-6 (IL-6) and interleukin-8 (IL-8) secretion by mucosal cells, and to promote wound healing in a fibroblast model. Using a microplate colorimetric assay, Rokumigan prevented biofilm formation by F. nucleatum, while it had no effect on bacterial growth. Rokumigan inhibited IL-6 secretion in both epithelial cells and fibroblasts stimulated with lipopolysaccharide. However, it caused no significant inhibition of IL-8 secretion by both cell types. Rokumigan significantly increased proliferation and migration of gingival fibroblasts in a wound healing assay. In conclusion, the Kampo formulation Rokumigan, through suppression of biofilm formation by F. nucleatum, inhibition of IL-6 secretion by gingival epithelial cells and fibroblasts, and promotion of wound healing in a fibroblast model, may have potential application for periodontal diseases.

  1. Canine pyometra: a model for the analysis of serum CXCL8 in inflammation.

    Science.gov (United States)

    Haas, Melanie; Kaup, Franz-Josef; Neumann, Stephan

    2016-03-01

    Interleukin-8 (IL-8 or CXCL8) is a highly selective pro-inflammatory chemokine, that is elevated in sera of humans and animals with various inflammatory diseases. CXCL8 is possibly involved in uncontrolled inflammation and the development of a systemic inflammatory response syndrome (SIRS) and sepsis. Nevertheless, its behavior and precise properties in the course of inflammation are not fully understood. Thus, we used naturally occurring canine pyometra as a model of inflammation, in order to examine the behavior of serum CXCL8 in relation to the disease intensity and commonly analyzed inflammatory mediators. Using a commercially available canine ELISA kit, a significant increase of CXCL8 was determined in the serum of 23 dogs with pyometra compared with 35 healthy dogs. Interestingly, serum CXCL8 did not increase in severely diseased patients and behaved contrary to white blood cells (WBC), neutrophils and C-reactive protein (CRP). The measurement of serum CXCL8 may provide valuable information about the extent of ongoing lesions and could be a useful complement for existing laboratory tests.

  2. Harnessing functional food strategies for the health challenges of space travel—Fermented soy for astronaut nutrition

    Science.gov (United States)

    Buckley, Nicole D.; Champagne, Claude P.; Masotti, Adriana I.; Wagar, Lisa E.; Tompkins, Thomas A.; Green-Johnson, Julia M.

    2011-04-01

    Astronauts face numerous health challenges during long-duration space missions, including diminished immunity, bone loss and increased risk of radiation-induced carcinogenesis. Changes in the intestinal flora of astronauts may contribute to these problems. Soy-based fermented food products could provide a nutritional strategy to help alleviate these challenges by incorporating beneficial lactic acid bacteria, while reaping the benefits of soy isoflavones. We carried out strain selection for the development of soy ferments, selecting strains of lactic acid bacteria showing the most effective growth and fermentation ability in soy milk ( Streptococcus thermophilus ST5, Bifidobacterium longum R0175 and Lactobacillus helveticus R0052). Immunomodulatory bioactivity of selected ferments was assessed using an in vitro challenge system with human intestinal epithelial and macrophage cell lines, and selected ferments show the ability to down-regulate production of the pro-inflammatory cytokine interleukin-8 following challenge with tumour necrosis factor-alpha. The impact of fermentation on vitamin B1 and B6 levels and on isoflavone biotransformation to agluconic forms was also assessed, with strain variation-dependent biotransformation ability detected. Overall this suggests that probiotic bacteria can be successfully utilized to develop soy-based fermented products targeted against health problems associated with long-term space travel.

  3. Antibiofilm and Anti-Inflammatory Activities of Houttuynia cordata Decoction for Oral Care

    Directory of Open Access Journals (Sweden)

    Yasuko Sekita

    2017-01-01

    Full Text Available Dental biofilms that form in the oral cavity play a critical role in the pathogenesis of several infectious oral diseases, including dental caries, periodontal disease, and oral candidiasis. Houttuynia cordata (HC, Saururaceae is a widely used traditional medicine, for both internal and external application. A decoction of dried HC leaves (dHC has long been consumed as a health-promoting herbal tea in Japan. We have recently reported that a water solution of HC poultice ethanol extract (wHCP exerts antimicrobial and antibiofilm effects against several important oral pathogens. It also exhibits anti-inflammatory effects on human keratinocytes. In our current study, we examined the effects of dHC on infectious oral pathogens and inflammation. Our results demonstrated that dHC exerts moderate antimicrobial effects against methicillin-resistant Staphylococcus aureus (MRSA and other oral microorganisms. dHC also exhibited antibiofilm effects against MRSA, Fusobacterium nucleatum (involved in dental plaque formation, and Candida albicans and inhibitory effects on interleukin-8, CCL20, IP-10, and GROα productions by human oral keratinocytes stimulated by Porphyromonas gingivalis lipopolysaccharide (a cause of periodontal disease, without cytotoxic effects. This suggests that dHC exhibits multiple activities in microorganisms and host cells. dHC can be easily prepared and may be effective in preventing infectious oral diseases.

  4. Effect of trans-chalcone on hepatic IL-8 through the regulation of miR-451 in male rats

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    Karimi-Sales Elham

    2018-01-01

    Full Text Available Objective. Trans-chalcone is a chalcone with hepatoprotective and anti-inflammatory effects. However, the mechanism of these positive effects, especially on miR-451 as an inflammatory regulator, is poorly understood. In this regard, this microRNA (miRNA acts by inhibition of hepatic interleukin-8 (IL-8 production in the liver which is one of the main proinflammatory cytokines. Th is study for the first time examined the effect of trans-chalcone on miR-451/IL-8 pathway. Methods. In present study, 21 male rats were randomly divided into 3 groups (n=7 per each group: control which received solvent (NS, groups 2 (N2T and 3 (N6T, which received transchalcone for 2 and 6 weeks, respectively. Hepatic level of miR-451 was measured by qRT-PCR. Serum levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST as well as hepatic level of IL-8 protein were measured. Results. Trans-chalcone decreased hepatic level of IL-8 protein and serum level of ALT aft er 2 weeks of treatment without significant change in hepatic miR-451. Moreover, it increased hepatic level of miR-451 and reduced hepatic IL-8 as well as AST and ALT aft er 6 weeks. Conclusion. Based on the results of present study, miR-451/IL-8 pathway is a possible mechanism for hepatoprotective action of trans-chalcone in long-term.

  5. Effect of cyclosporin A on inflammatory cytokine production by U937 monocyte-like cells

    Directory of Open Access Journals (Sweden)

    Juan E. Losa Garcia

    2000-01-01

    Full Text Available Cyclosporin A (CsA is an immunosuppresor drug that has been used in the treatment of several types of inflammatory diseases. In some of them the inhibition of T-lymphocyte activation does not suitably account for the observed beneficial effect, suggesting that CsA could act on other types of cells. The present study was undertaken to determine the effect of CsA on inflammatory cytokine secretion by U937 monocyte cells. Undifferentiated and dimethylsulfoxide (DMSO differentiated U937 cells were incubated with different concentrations of CsA (200, 20 and 2 ng/mL in the presence or absence of phorbol-myristateacetate (PMA. Interleukin-1g (IL-1β, tumor necrosis factor-α (TNF-α, IL-6 and IL-8 levels were measured in supernatants using specific enzyme-linked immunosorbent assays. At the highest concentration used (200 ng/mL CsA decreased the basal and stimulated secretion of all the inflammatory cytokines studied in both undifferentiated and differentiated cells, with the only exception of PMA-stim ulated IL-1 secretion by undifferentiated cells. However, only basal secretion of interleukin-8 in both undifferentiated and DMSO-differentiated U937 cells was significantly reduced by CsA at the highest concentration (200 ng/ mL. At therapeutic concentrations in vivo, CsA exerts a predominant effect on IL-8 secretion by human mononuclear phagocytes.

  6. Advances in Understanding How Heavy Metal Pollution Triggers Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Wenzhen Yuan

    2016-01-01

    Full Text Available With the development of industrialization and urbanization, heavy metals contamination has become a major environmental problem. Numerous investigations have revealed an association between heavy metal exposure and the incidence and mortality of gastric cancer. The mechanisms of heavy metals (lead, cadmium, mercury, chromium, and arsenic contamination leading to gastric cancer are concluded in this review. There are four main potential mechanisms: (1 Heavy metals disrupt the gastric mucosal barrier by decreasing mucosal thickness, mucus content, and basal acid output, thereby affecting the function of E-cadherin and inducing reactive oxygen species (ROS damage. (2 Heavy metals directly or indirectly induce ROS generation and cause gastric mucosal and DNA lesions, which subsequently alter gene regulation, signal transduction, and cell growth, ultimately leading to carcinogenesis. Exposure to heavy metals also enhances gastric cancer cell invasion and metastasis. (3 Heavy metals inhibit DNA damage repair or cause inefficient lesion repair. (4 Heavy metals may induce other gene abnormalities. In addition, heavy metals can induce the expression of proinflammatory chemokine interleukin-8 (IL-8 and microRNAs, which promotes tumorigenesis. The present review is an effort to underline the human health problem caused by heavy metal with recent development in order to garner a broader perspective.

  7. Advances in Understanding How Heavy Metal Pollution Triggers Gastric Cancer.

    Science.gov (United States)

    Yuan, Wenzhen; Yang, Ning; Li, Xiangkai

    2016-01-01

    With the development of industrialization and urbanization, heavy metals contamination has become a major environmental problem. Numerous investigations have revealed an association between heavy metal exposure and the incidence and mortality of gastric cancer. The mechanisms of heavy metals (lead, cadmium, mercury, chromium, and arsenic) contamination leading to gastric cancer are concluded in this review. There are four main potential mechanisms: (1) Heavy metals disrupt the gastric mucosal barrier by decreasing mucosal thickness, mucus content, and basal acid output, thereby affecting the function of E-cadherin and inducing reactive oxygen species (ROS) damage. (2) Heavy metals directly or indirectly induce ROS generation and cause gastric mucosal and DNA lesions, which subsequently alter gene regulation, signal transduction, and cell growth, ultimately leading to carcinogenesis. Exposure to heavy metals also enhances gastric cancer cell invasion and metastasis. (3) Heavy metals inhibit DNA damage repair or cause inefficient lesion repair. (4) Heavy metals may induce other gene abnormalities. In addition, heavy metals can induce the expression of proinflammatory chemokine interleukin-8 (IL-8) and microRNAs, which promotes tumorigenesis. The present review is an effort to underline the human health problem caused by heavy metal with recent development in order to garner a broader perspective.

  8. Structurally Distinct Bacterial TBC-like GAPs Link Arf GTPase to Rab1 Inactivation to Counteract Host Defenses

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Na; Zhu, Yongqun; Lu, Qiuhe; Hu, Liyan; Zheng, Yuqing; Shao, Feng (NIBS-China); (Zhejiang)

    2012-10-10

    Rab GTPases are frequent targets of vacuole-living bacterial pathogens for appropriate trafficking of the vacuole. Here we discover that bacterial effectors including VirA from nonvacuole Shigella flexneri and EspG from extracellular Enteropathogenic Escherichia coli (EPEC) harbor TBC-like dual-finger motifs and exhibits potent RabGAP activities. Specific inactivation of Rab1 by VirA/EspG disrupts ER-to-Golgi trafficking. S. flexneri intracellular persistence requires VirA TBC-like GAP activity that mediates bacterial escape from autophagy-mediated host defense. Rab1 inactivation by EspG severely blocks host secretory pathway, resulting in inhibited interleukin-8 secretion from infected cells. Crystal structures of VirA/EspG-Rab1-GDP-aluminum fluoride complexes highlight TBC-like catalytic role for the arginine and glutamine finger residues and reveal a 3D architecture distinct from that of the TBC domain. Structure of Arf6-EspG-Rab1 ternary complex illustrates a pathogenic signaling complex that rewires host Arf signaling to Rab1 inactivation. Structural distinctions of VirA/EspG further predict a possible extensive presence of TBC-like RabGAP effectors in counteracting various host defenses.

  9. Mediadores inflamatórios, citograma em lavado nasal e tomografia computadorizada de seios paranasais em crianças atópicas Inflammatory mediators, cell counts in nasal lavage and computed tomography of the paranasal sinuses in atopic children

    Directory of Open Access Journals (Sweden)

    Loreni C.S. Kovalhuk

    2001-08-01

    mucosa paranasal está associado à eosinofilia periférica e do lavado nasal e à ativação celular. A infiltração e a ativação de neutrófilos não estavam relacionadas com a maior extensão de lesão da mucosa paranasal.OBJECTIVE: The aims of this study were to evaluate inflammatory cells, the profile of inflammatory mediators in nasal lavage (NL, and the involvement of the paranasal mucosa in atopic infants with no symptoms of sinusitis. METHODS: 48 atopic patients with allergic rhinitis (AR, and 33/48 patients with asthma were studied; the control group consisted of 13 nonatopic children. Those individuals with acute, chronic or recurrent sinusitis were excluded. The involvement of the paranasal mucosa was assessed by coronal computed tomography (CT and graded by a standard protocol (0-30. A CT score greater than or equal to 12 indicated extensive involvement. Nasal lavage was used to quantify total and differential nasal cell counts. An aliquot of the supernatant was used for determining inflammatory mediators: interleukin-8 (IL-8, myeloperoxidase (MPO, and eosinophil cationic protein (ECP. Albumin was used as a marker for increased vascular permeability. These measurements were performed on all of the atopic patients and in 6/13 patients in the control group. The three groups were submitted to spirometry and complete blood cell count. RESULTS: Extensive involvement of the paranasal mucosa was observed in 7/33 (21% of asthmatic patients (Group I and 2/15 (13% of those with allergic rhinitis (Group II. The highest CT score in the control group (Group III was 7. Total cell and eosinophil count/ml and albumin concentration in nasal fluid were higher in asthmatic patients whose CT score was greater than 12. Interleukin-8 concentration, number of neutrophils and epithelial cells/ml in nasal fluid were similar in the three groups. A positive correlation between CT score, peripheral blood eosinophilia, number of eosinophils/ml and eosinophil cationic protein

  10. Purine-Metabolizing Ectoenzymes Control IL-8 Production in Human Colon HT-29 Cells

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    Fariborz Bahrami

    2014-01-01

    Full Text Available Interleukin-8 (IL-8 plays key roles in both chronic inflammatory diseases and tumor modulation. We previously observed that IL-8 secretion and function can be modulated by nucleotide (P2 receptors. Here we investigated whether IL-8 release by intestinal epithelial HT-29 cells, a cancer cell line, is modulated by extracellular nucleotide metabolism. We first identified that HT-29 cells regulated adenosine and adenine nucleotide concentration at their surface by the expression of the ectoenzymes NTPDase2, ecto-5′-nucleotidase, and adenylate kinase. The expression of the ectoenzymes was evaluated by RT-PCR, qPCR, and immunoblotting, and their activity was analyzed by RP-HPLC of the products and by detection of Pi produced from the hydrolysis of ATP, ADP, and AMP. In response to poly (I:C, with or without ATP and/or ADP, HT-29 cells released IL-8 and this secretion was modulated by the presence of NTPDase2 and adenylate kinase. Taken together, these results demonstrate the presence of 3 ectoenzymes at the surface of HT-29 cells that control nucleotide levels and adenosine production (NTPDase2, ecto-5′-nucleotidase and adenylate kinase and that P2 receptor-mediated signaling controls IL-8 release in HT-29 cells which is modulated by the presence of NTPDase2 and adenylate kinase.

  11. In vitro toxicity of zinc oxide nanoparticles: a review

    Energy Technology Data Exchange (ETDEWEB)

    Pandurangan, Muthuraman; Kim, Doo Hwan, E-mail: frenzram1980@gmail.com [Konkuk University, Department of Bioresources and Food Sciences (Korea, Republic of)

    2015-03-15

    The toxic effect of ZnO nanoparticles is due to their solubility. ZnO nanoparticles dissolve in the extracellular region, which in turn increases the intracellular [Zn{sup 2+}] level. The mechanism for increased intracellular [Zn{sup 2+}] level and ZnO nanoparticles dissolution in the medium is still unclear. Cytotoxicity, increased oxidative stress, increased intracellular [Ca{sup 2+}] level, decreased mitochondrial membrane potential, and interleukin-8 productions occur in the BEAS-2B bronchial epithelial cells and A549 alveolar adenocarcinoma cells following the exposure of ZnO nanoparticles. Confluent C2C12 cells are more resistant to ZnO nanoparticles compared to the sparse monolayer. Loss of 3T3-L1 cell viability, membrane leakage, and morphological changes occurs due to exposure of ZnO nanoparticles. ZnO nanoparticle induces cytotoxicity and mitochondrial dysfunction in RKO colon carcinoma cells. The occurrence of apoptosis, increased ROS level, reduced mitochondrial activity and formation of tubular intracellular structures are reported following exposure of ZnO nanoparticles in skin cells. Macrophages, monocytes, and dendritic cells are affected by ZnO nanoparticles. In addition, genotoxicity is also induced. The present review summarizes the literature on in vitro toxicity of ZnO nanoparticles (10–100 nm) on various cell lines.

  12. Endostatin improves radioresponse and blocks tumor revascularization after radiation therapy for A431 xenografts in mice

    International Nuclear Information System (INIS)

    Itasaka, Satoshi; Komaki, Ritsuko; Herbst, Roy S.; Shibuya, Keiko; Shintani, Tomoaki D.D.S.; Hunter, Nancy R. M.S.; Onn, Amir; Bucana, Corazon D.; Milas, Luka; Ang, K. Kian; O'Reilly, Michael S.

    2007-01-01

    Purpose: Clinical trials of antiangiogenic agents used alone for advanced malignancy have been disappointing but preclinical studies suggest that the addition of radiation therapy could improve antitumor efficacy. To test the hypothesis that antiangiogenic therapy combined with radiation therapy can overcome the limitations of antiangiogenic monotherapy, we studied the effects of endostatin combined with radiation on the growth and vascularization of A431 human epidermoid carcinomas growing intramuscularly in the legs of mice. Methods and Materials: Mice with established A431 human epidermoid leg tumors were treated with radiation, endostatin, both radiation and endostatin, or vehicle control. The experiment was repeated and mice from each group were killed at 2, 7, and 10 days after irradiation so that tumor tissue could be obtained to further analyze the kinetics of the antitumor, antivascular, and antiangiogenic response to therapy. Results: Endostatin enhanced the antitumor effects of radiation, and prolonged disease-free survival was observed in the combined treatment group. Endothelial cell proliferation was increased in tumors after irradiation but was blocked by the concurrent administration of endostatin, and the combination of endostatin with radiation enhanced endothelial cell apoptosis within 48 h after irradiation. Expression of vascular endothelial growth factor, interleukin-8, and matrix metalloproteinase-2 were increased in tumors after irradiation, and this increase was blocked by concurrent administration of endostatin. Conclusion: These data indicate that endostatin can block tumor revascularization after radiation therapy and thereby augment radioresponse

  13. An investigation of the relationship between the anti-inflammatory activity, polyphenolic content, and antioxidant activities of cooked and in vitro digested culinary herbs.

    Science.gov (United States)

    Chohan, Magali; Naughton, Declan P; Jones, Lucy; Opara, Elizabeth I

    2012-01-01

    There is little research on how cooking and digestion affect the anti-inflammatory activity of culinary herbs. Thus, the aim of this paper was to investigate this activity following cooking and in vitro digestion of the common culinary herbs, rosemary, sage, and thyme, and the relationship between their anti-inflammatory activity, polyphenol content, and antioxidant capacity. The anti-inflammatory activity of uncooked (U), cooked (C), cooked and in vitro digested (C&D), and standardised (STD, 30 mg/mL) culinary herbs was assessed by measuring their effect on interleukin 8 (IL-8) release from stimulated human peripheral blood lymphocytes (PBLs) and Caco-2 cells. The trolox equivalent capacity (TEAC) and estimated total phenolic content of the herbs were also determined. There was a significant decrease in IL-8 release from PBLs stimulated with H(2)O(2) incubated with (U), (C), (C&D), and (STD) herbs and from Caco-2 cells stimulated with TNFα incubated with (C&D) and (STD) herbs. PBLs pre-incubated with (C&D) herbs prior to stimulation (H(2)O(2) or TNFα) caused a significant inhibition in IL-8 release. The significant correlations between TEAC and estimated phenolic content and the anti-inflammatory activity suggest a possible contributory role of polyphenols to the anti-inflammatory activity of the culinary herbs investigated.

  14. Oral keratinocyte immune responses in HIV-associated candidiasis.

    Science.gov (United States)

    Eversole, L R; Reichart, P A; Ficarra, G; Schmidt-Westhausen, A; Romagnoli, P; Pimpinelli, N

    1997-10-01

    Candidiasis is the most commonly encountered opportunistic infection among HIV-positive subjects. The purpose of this study was to assess specific keratinocyte immune parameters in the pseudomembranous and erythematous forms of HIV-associated oral candidiasis. This collaborative study from three centers analyzed 25 HIV-positive and 10 HIV-negative subjects with either pseudomembranous or erythematous candidiasis. Oral biopsy specimens from lesional tissues were procured, and histopathologic features were correlated with immunohistochemical and in situ hybridization investigations for the expression of interleukin 1 alpha, interleukin 8, antimicrobial calprotectin, lymphocyte populations, and Candida antigen. Both pseudomembranous and erythematous candidiasis among HIV-infected subjects showed a mild interface lymphocytic mucositis with the presence of neutrophilic subcorneal abscesses in the latter. Erythematous candidiasis cases that failed to show surface mycelia, did yield positive results for Candida antigens in the parakeratinized layer. The expression of inflammatory chemokines were positive in all groups and calprotectin appeared to serve as a keratinocyte barrier to hyphal penetration. The erythematous form of candidiasis is often devoid of hyphae yet the presence of Candida antigens in the surface epithelium implicates an immune or allergic process. The intactness of chemokines and antimicrobial calprotectin in keratinocytes may explain why disseminated candidiasis is rarely encountered in HIV-infected patients.

  15. Rat inhalation test with particles from biomass combustion and biomass co-firing exhaust

    International Nuclear Information System (INIS)

    Bellmann, B; Creutzenberg, O; Ernst, H; Muhle, H

    2009-01-01

    The health effects of 6 different fly ash samples from biomass combustion plants (bark, wood chips, waste wood, and straw), and co-firing plants (coal, co-firing of coal and sawdust) were investigated in a 28-day nose-only inhalation study with Wistar WU rats. Respirable fractions of carbon black (Printex 90) and of titanium dioxide (Bayertitan T) were used as reference materials for positive and negative controls. The exposure was done 6 hours per day, 5 days per week at an aerosol concentration of 16 mg/m 3 . The MMAD of all fly ash samples and reference materials in the inhalation unit were in the range from 1.5 to 3 μm. The investigations focused predominantly on the analysis of inflammatory effects in the lungs of rats using bronchoalveolar lavage (BAL) and histopathology. Different parameters (percentage of polymorphonuclear neutrophils (PMN), interleukin-8 and interstitial inflammatory cell infiltration in the lung tissue) indicating inflammatory effects in the lung, showed a statistically significant increase in the groups exposed to carbon black (positive control), C1 (coal) and C1+BM4 (co-firing of coal and sawdust) fly ashes. Additionally, for the same groups a statistically significant increase of cell proliferation in the lung epithelium was detected. No significant effects were detected in the animal groups exposed to BM1 (bark), BM2 (wood chips), BM3 (waste wood), BM6 (straw) or titanium dioxide.

  16. Molecular mechanisms of Porphyromonas gingivalis-host cell interaction on periodontal diseases

    Directory of Open Access Journals (Sweden)

    Masaaki Nakayama

    2017-11-01

    Full Text Available Porphyromonas gingivalis (P. gingivalis is a major oral pathogen and associated with periodontal diseases including periodontitis and alveolar bone loss. In this review, we indicate that two virulence factors, which are hemoglobin receptor protein (HbR and cysteine proteases “gingipains”, expressed by P. gingivalis have novel functions on the pathogenicity of P. gingivalis. P. gingivalis produces three types of gingipains and concomitantly several adhesin domains. Among the adhesin domains, hemoglobin receptor protein (HbR, also called HGP15, has the function of induction of interleukin-8 (IL-8 expression in human gingival epithelial cells, indicating the possibility that HbR is associated with P. gingivalis-induced periodontal inflammation. On bacteria-host cells contact, P. gingivalis induces cellular signaling alteration in host cells. Phosphatidylinositol 3-kinase (PI3K and Akt are well known to play a pivotal role in various cellular physiological functions including cell survival and glucose metabolism in mammalian cells. Recently, we demonstrated that gingipains attenuate the activity of PI3K and Akt, which might have a causal influence on periodontal diseases by chronic infection to the host cells from the speculation of molecular analysis. In this review, we discuss new molecular and biological characterization of the virulence factors from P. gingivalis.

  17. Reactive oxygen species in periodontitis

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    Parveen Dahiya

    2013-01-01

    Full Text Available Recent epidemiological studies reveal that more than two-third of the world′s population suffers from one of the chronic forms of periodontal disease. The primary etiological agent of this inflammatory disease is a polymicrobial complex, predominantly Gram negative anaerobic or facultative bacteria within the sub-gingival biofilm. These bacterial species initiate the production of various cytokines such as interleukin-8 and TNF-α, further causing an increase in number and activity of polymorphonucleocytes (PMN along with these cytokines, PMNs also produce reactive oxygen species (ROS superoxide via the respiratory burst mechanism as the part of the defence response to infection. ROS just like the interleukins have deleterious effects on tissue cells when produced in excess. To counter the harmful effects of ROS, human body has its own defence mechanisms to eliminate them as soon as they are formed. The aim of this review is to focus on the role of different free radicals, ROS, and antioxidants in the pathophysiology of periodontal tissue destruction.

  18. Stromal Interaction Molecule 1 (STIM1) and Orai1 Mediate Histamine-evoked Calcium Entry and Nuclear Factor of Activated T-cells (NFAT) Signaling in Human Umbilical Vein Endothelial Cells*

    Science.gov (United States)

    Zhou, Meng-Hua; Zheng, Hongying; Si, Hongjiang; Jin, Yixin; Peng, Jasmine M.; He, Lian; Zhou, Yubin; Muñoz-Garay, Carlos; Zawieja, David C.; Kuo, Lih; Peng, Xu; Zhang, Shenyuan L.

    2014-01-01

    Histamine is an important immunomodulator involved in allergic reactions and inflammatory responses. In endothelial cells, histamine induces Ca2+ mobilization by releasing Ca2+ from the endoplasmic reticulum and eliciting Ca2+ entry across the plasma membrane. Herein, we show that histamine-evoked Ca2+ entry in human umbilical vein endothelial cells (HUVECs) is sensitive to blockers of Ca2+ release-activated Ca2+ (CRAC) channels. RNA interference against STIM1 or Orai1, the activating subunit and the pore-forming subunit of CRAC channels, respectively, abolishes this histamine-evoked Ca2+ entry. Furthermore, overexpression of dominant-negative CRAC channel subunits inhibits while co-expression of both STIM1 and Orai1 enhances histamine-induced Ca2+ influx. Interestingly, gene silencing of STIM1 or Orai1 also interrupts the activation of calcineurin/nuclear factor of activated T-cells (NFAT) pathway and the production of interleukin 8 triggered by histamine in HUVECs. Collectively, these results suggest a central role of STIM1 and Orai1 in mediating Ca2+ mobilization linked to inflammatory signaling of endothelial cells upon histamine stimulation. PMID:25190815

  19. Development of an in Vitro Potency Assay for Anti-anthrax Lethal Toxin Neutralizing Antibodies

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    Sjoerd Rijpkema

    2012-01-01

    Full Text Available Lethal toxin (LT of Bacillus anthracis reduces the production of a number of inflammatory mediators, including transcription factors, chemokines and cytokines in various human cell lines, leading to down-regulation of the host inflammatory response. Previously we showed that the reduction of interleukin-8 (IL-8 is a sensitive marker of LT-mediated intoxication in human neutrophil-like NB-4 cells and that IL-8 levels are restored to normality when therapeutic monoclonal antibodies (mAb with toxin-neutralising (TN activity are added. We used this information to develop cell-based assays that examine the effects of TN therapeutic mAbs designed to treat LT intoxication and here we extend these findings. We present an in vitro assay based on human endothelial cell line HUVEC jr2, which measures the TN activity of therapeutic anti-LT mAbs using IL-8 as a marker for intoxication. HUVEC jr2 cells have the advantage over NB-4 cells that they are adherent, do not require a differentiation step and can be used in a microtitre plate format and therefore can facilitate high throughput analysis. This human cell-based assay provides a valid alternative to the mouse macrophage assay as it is a more biologically relevant model of the effects of toxin-neutralising antibodies in human infection.

  20. Angiogenic/lymphangiogenic factors and adaptation to extreme altitudes during an expedition to Mount Everest.

    Science.gov (United States)

    Patitucci, M; Lugrin, D; Pagès, G

    2009-06-01

    To analyse the correlation between production of angiogenic [vascular endothelial growth factor A (VEGF-A) and interleukin 8 (IL-8)] and lymphangiogenic factors (VEGF-C and D) and adaptation to high altitude (>8000 m). Erythropoietin (EPO) served as a positive control. We analysed the percentage of oxygen saturation and the plasmatic contents of VEGF-A, C, D, IL-8 and EPO in seven mountaineers and four Sherpas during an expedition to Mount Everest. Acute mountain sickness was also evaluated using the Lake Louise score. Whereas VEGF-A, IL-8, VEGF-C and EPO were transiently up-regulated at 5000 m and decreased at the highest altitudes, VEGF-D remained elevated throughout the ascent. Sherpas had increased basal levels of VEGF-A, C, IL-8 and EPO and up-regulation of all the tested factors when they passed the altitude at which they lived. Our data suggest that expression of angiogenic and lymphangiogenic factors is up-regulated directly or indirectly by altitude-dependent hypoxia. Both factors could be involved in a mechanism of adaptation to high altitudes.

  1. Inflammation-Induced Downregulation of Butyrate Uptake and Oxidation Is Not Caused by a Reduced Gene Expression.

    Science.gov (United States)

    Boesmans, Leen; Ramakers, Meine; Arijs, Ingrid; Windey, Karen; Vanhove, Wiebe; Schuit, Frans; Rutgeerts, Paul; Verbeke, Kristin; De Preter, Vicky

    2015-02-01

    In ulcerative colitis (UC) the butyrate metabolism is impaired, leading to energy-deficiency in the colonic cells. The effect of inflammation on the butyrate metabolism was investigated. HT-29 cells were incubated with pro-inflammatory cytokines (TNF-α and/or IFN-γ) for 1 and 24 h. Cells were additionally stimulated with butyrate to investigate its anti-inflammatory potential. Butyrate uptake and oxidation were measured using (14)C-labeled butyrate. Gene expression of the butyrate metabolism enzymes, interleukin 8 (IL-8; inflammatory marker) and villin-1 (VIL-1; epithelial cell damage marker) was measured via quantitative RT-PCR. Significantly increased IL-8 expression and decreased VIL-1 expression after 24 h incubation with TNF-α and/or IFN-γ confirmed the presence of inflammation. These conditions induced a decrease of both butyrate uptake and oxidation, whereas the gene expression was not reduced. Simultaneous incubation with butyrate counteracted the reduced butyrate oxidation. In contrast, 1 h incubation with TNF-α induced a significant increased IL-8 expression and decreased butyrate uptake. Incubation with TNF-α and/or IFN-γ for 1 h did not induce cell damage nor influence butyrate oxidation. The inflammation-induced downregulation of the butyrate metabolism was not caused by a reduced gene expression, but appeared consequential to a decreased butyrate uptake. Increasing the luminal butyrate levels might have therapeutic potential in UC. © 2014 Wiley Periodicals, Inc.

  2. Properties and inflammatory effects of various size fractions of ambient particulate matter from Beijing on A549 and J774A.1 cells.

    Science.gov (United States)

    Wang, Bin; Li, Kexin; Jin, Wenjie; Lu, Yan; Zhang, Yuzhong; Shen, Guofeng; Wang, Rong; Shen, Huizhong; Li, Wei; Huang, Ye; Zhang, Yanyan; Wang, Xilong; Li, Xiqing; Liu, Wenxin; Cao, Hongying; Tao, Shu

    2013-09-17

    Particulate matter (PM) is a major ambient air pollutant causing millions of premature deaths each year in China. The toxicity of PM is property and size dependent. In this study, ambient PM samples collected in Beijing were divided into five size fractions with nominal aerodynamic ranges of properties including particle size distribution, specific surface area, zeta potential, dithiothreitol (DTT)-based redox ability, and contents of water-soluble organic carbon (WSOC), polycyclic aromatic hydrocarbons (PAHs), selected metals, and endotoxin. Human adenocarcinomic alveolar epithelial cell line A549 and small mouse monocyte-macrophage cell line J774A.1 were tested for their relative viabilities and inflammatory effects (interleukine-8 for A549 and tumor necrosis factor-α for J774A.1) after exposure to PM of various sizes. It was found that PM specific area was positively correlated with WSOC, high molecular weight PAHs, DTT-based redox ability, negatively correlated with surface zeta potential and lithophile metals. Several trace metals from combustion sources were enriched in intermediate size fractions. For both endotoxin concentrations of the PM and PM induced inflammatory cytokine expressions by the two cell lines, there were general increasing trends as PM size increased with an exception of the finest fraction, which induced the highest inflammatory effects. It seems that the size dependence of cytokine expression was associated with a number of properties including endotoxin content, zeta potential, settling velocity, metal content, and DTT-based redox ability.

  3. Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Yang, Lei; Jiao, Xingai; Wu, Jinxiang; Zhao, Jiping; Liu, Tian; Xu, Jianfeng; Ma, Xiaohui; Cao, Liuzao; Liu, Lin; Liu, Yahui; Chi, Jingyu; Zou, Minfang; Li, Shuo; Xu, Jiawei; Dong, Liang

    2018-03-01

    Cordyceps sinensis is a traditional Chinese herbal medicine that has been used for centuries in Asia as a tonic to soothe the lung for the treatment of respiratory diseases. The aim of the present study was to determine the effects of C. sinensi s on airway remodeling in chronic obstructive pulmonary disease (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were orally administered C. sinensis at low, moderate or high doses (2.5, 5 or 7.5 g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung inflammation and airway remodeling were evaluated. C. sinensis treatment significantly ameliorated airway wall thickening, involving collagen deposition, airway wall fibrosis, smooth muscle hypertrophy and epithelial hyperplasia in model rats with COPD. Additionally, C. sinensis administration in rats with COPD reduced inflammatory cell accumulation and decreased inflammatory cytokine production, including tumor necrosis factor-α, interleukin-8 and transforming growth factor (TGF)-β1 in bronchoalveolar lavage fluid. Meanwhile, the increased levels of α-smooth muscle actin and collagen I in the COPD group were also markedly decreased by C. sinensis treatment. Furthermore, compared with untreated rats with COPD, C. sinensis reduced the expression level of phosphorylated (p)-Smad2, p-Smad3, TGF-β1 and its receptors, with the concomitant increased expression of Smad7 in the lungs of rats with COPD. These results indicated that treatment with C. sinensis may be a useful approach for COPD therapy.

  4. The impact of intermittent and repetitive cold stress exposure on endoplasmic reticulum stress and instability of atherosclerotic plaques.

    Science.gov (United States)

    Dai, Ming-Xiang; Zheng, Xiao-Hui; Yu, Jin; Yin, Tao; Ma, Mei-Juan; Zhang, Le; Liu, Min; Ma, Ying; Liu, Li-Wen; Gao, Xue; Li, Yan; Song, Li-Qiang; Wang, Hai-Chang

    2014-01-01

    The incidence of acute coronary syndrome caused by the rupture of atherosclerotic plaque and subsequent arterial thrombosis increases as the weather gets colder. However, the association between cold stress and atherosclerotic plaque rupture is currently unknown. An atherosclerotic plaque model was established in rabbits by balloon injury and a high-fat diet with or without cold stress (4 °C, 1 hour per day, 20 weeks) at the onset of modeling. Additionally, oxidized low-density lipoprotein (ox-LDL) was applied to induce the formation of macrophage foam cells in vitro. Serum lipid profiles and inflammatory cytokines (ox-LDL, high-sensitivity C-reactive protein, and interleukin-8) were significantly higher in cold stress-exposed rabbits than in controls (Pinstability of atherosclerotic plaques through activating ERS and enhancing cell apoptosis. Up-regulated CHOP levels mediated by PERK and ATF6 and the activated IRE1-XBP1-JNK pathway contributed to the apoptosis of foam cells. © 2014 S. Karger AG, Basel.

  5. The Impact of Intermittent and Repetitive Cold Stress Exposure on Endoplasmic Reticulum Stress and Instability of Atherosclerotic Plaques

    Directory of Open Access Journals (Sweden)

    Ming-Xiang Dai

    2014-07-01

    Full Text Available Background: The incidence of acute coronary syndrome caused by the rupture of atherosclerotic plaque and subsequent arterial thrombosis increases as the weather gets colder. However, the association between cold stress and atherosclerotic plaque rupture is currently unknown. Methods: An atherosclerotic plaque model was established in rabbits by balloon injury and a high-fat diet with or without cold stress (4°C, 1 hour per day, 20 weeks at the onset of modeling. Additionally, oxidized low-density lipoprotein (ox-LDL was applied to induce the formation of macrophage foam cells in vitro. Results: Serum lipid profiles and inflammatory cytokines (ox-LDL, high-sensitivity C-reactive protein, and interleukin-8 were significantly higher in cold stress-exposed rabbits than in controls (PConclusions: Cold stress may enhance the instability of atherosclerotic plaques through activating ERS and enhancing cell apoptosis. Up-regulated CHOP levels mediated by PERK and ATF6 and the activated IRE1-XBP1-JNK pathway contributed to the apoptosis of foam cells.

  6. The physiological role of hormones in saliva.

    Science.gov (United States)

    Gröschl, Michael

    2009-08-01

    The assessment of hormones in saliva has gained wide acceptance in clinical endocrinology. To date, there is no hypothesis as to why some hormones can be found in saliva, while others cannot, and whether there is a physiological consequence of this fact. A number of carefully performed studies give examples of important physiological hormonal activity in saliva. Steroids, such as androgens, act as pheromones in olfactory communication of various mammalian species, such as facilitating mating behavior in swine or serving as odor cues for rodent nestlings. Salivary peptide hormones, such as epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha), and amines such as melatonin, are involved in the regulation of inflammatory processes and in the promotion of cell proliferation, and contribute to a rapid wound healing in the oropharyngeal epithelia. Current data provide evidence of the involvement of salivary cytokines, such as interleukin-8 and leptin, in tumorgenesis in the oral cavity and the salivary glands. The tumor tissues express and release significantly more of these cytokines than healthy glands. Consequently, the assessment of salivary hormone profiles may provide promising targets for diagnostic tumor markers.

  7. Possible role for interleukins as biomarkers for mortality and recurrence in oral cancer.

    Science.gov (United States)

    Arduino, Paolo G; Menegatti, Elisa; Cappello, Nazario; Martina, Eugenio; Gardino, Nicolò; Tanteri, Carlotta; Cavallo, Franco; Scully, Crispian; Broccoletti, Roberto

    2015-05-26

    Salivary and serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have previously been studied in oral cancer with conflicting results. We designed a controlled study to assess the correlation between pretreatment salivary and serum levels of IL-6 and IL-8, and all-cause survival and cancer recurrence in oral cancer patients. Fifty-two oral cancer patients and 52 healthy control cases were selected. In univariate analysis, salivary IL-6 and IL-8 seemed to be more expressed in cases (p<0.001 and p = 0.010, respectively). Multivariate analysis showed that higher pretreatment saliva IL-6 levels were significantly associated with better survival (hazard ratio [HR] = 8.62; 95% confidence interval [95% CI], 1.21-62.50; p = 0.031). To date, this is the largest prospective controlled study that has analyzed the pretreatment salivary and serum levels of IL-6 and IL-8 in oral cancer patients, suggesting salivary IL-6 as a possible prognostic biomarker. But further validation in a larger sample is still necessary.

  8. Microinflammation Factors in the Common Diseases of the Heart and Kidneys

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    Danijela Tasic

    2015-01-01

    Full Text Available Aim. To determine levels of interleukin-8 (IL-8 and plasminogen activator inhibitor-1 (PAI-1 in different cardiorenal syndrome (CRS modalities and to compare findings to some already investigated direct and indirect parameters of inflammation and atherosclerosis. Materials and Methods. Testing involved 114 examinees, divided into control and clinical groups suffering from different modalities and were formed according to the basis of a valid classification for CRS. Results. C-reactive protein (CRP was significantly higher in all CRSs in comparison to the control group P<0.05. PAI-1 in CRSs was statistically higher than in the control group. IL-8 was increased in all CRSs, and especially in CRS-5, where no significance was found. PAI-1 correlated with IL-8 in all CRSs, with significant value in CRS-2 and CRS-5. Correlation for PAI-1 and high-density lipoproteins (HDL was found in CRS-4, while IL-8 was found to be related to CRP level in all CRSs, with significance only in CRS-1 P<0.001. Conclusions. C-reactive protein, IL-8, and PAI-1 could be useful for clinical differentiation of chronic modalities of CRSs. Inflammation was the most pronounced in CRS-4. Lipid status parameters could be useful for differentiation of CRSs. Furthermore, HDL in chronic primary kidney diseases and triglycerides and total cholesterol in CRS-5 could be valuable.

  9. Kefir-isolated bacteria and yeasts inhibit Shigella flexneri invasion and modulate pro-inflammatory response on intestinal epithelial cells.

    Science.gov (United States)

    Bolla, P A; Abraham, A G; Pérez, P F; de Los Angeles Serradell, M

    2016-02-01

    The aim of this work was to evaluate the ability of a kefir-isolated microbial mixture containing three bacterial and two yeast strains (MM) to protect intestinal epithelial cells against Shigella flexneri invasion, as well as to analyse the effect on pro-inflammatory response elicited by this pathogen. A significant decrease in S. flexneri strain 72 invasion was observed on both HT-29 and Caco-2 cells pre-incubated with MM. Pre-incubation with the individual strains Saccharomyces cerevisiae CIDCA 8112 or Lactococcus lactis subsp. lactis CIDCA 8221 also reduced the internalisation of S. flexneri into HT-29 cells although in a lesser extent than MM. Interestingly, Lactobacillus plantarum CIDCA 83114 exerted a protective effect on the invasion of Caco-2 and HT-29 cells by S. flexneri. Regarding the pro-inflammatory response on HT-29 cells, S. flexneri infection induced a significant activation of the expression of interleukin 8 (IL-8), chemokine (C-C motif) ligand 20 (CCL20) and tumour necrosis factor alpha (TNF-α) encoding genes (Pkefir, resulted in inhibition of S. flexneri internalisation into human intestinal epithelial cells, along with the inhibition of the signalling via NF-κB that in turn led to the attenuation of the inflammatory response.

  10. Analysis of chemokines and reactive oxygen species formation by rat and human neutrophils induced by microcystin-LA, -YR and -LR.

    Science.gov (United States)

    Kujbida, Paula; Hatanaka, Elaine; Campa, Ana; Curi, Rui; Poliselli Farsky, Sandra Helena; Pinto, Ernani

    2008-06-01

    Microcystins (MC), a family of heptapeptide toxins produced by some genera of Cyanobacteria, have potent hepatotoxicity and tumor-promoting activity. Leukocyte infiltration in the liver was observed in MC-induced acute intoxication. Although the mechanisms of hepatotoxicity are still unclear, neutrophil infiltration in the liver may play an important role in triggering toxic injury and tumor development. The present study reports the effects of MC-LA, MC-YR and MC-LR (1 and 1000 nM) on human and rat neutrophils functions in vitro. Cell viability, DNA fragmentation, mitochondrial membrane depolarization and intracellular reactive oxygen species (ROS) levels were measured by flow cytometry. Extracellular ROS content was measured by lucigenin-amplified chemiluminescence, and cytokines were determined by ELISA. We found that these MC increased interleukin-8 (IL-8), cytokine-induced neutrophil chemoattractant-2alphabeta (CINC-2alphabeta) and extracellular ROS levels in human and rat neutrophils. Apart from neutrophil presence during the inflammatory process of MC-induced injury, our results suggest that hepatic neutrophil accumulation is further increased by MC-induced neutrophil-derived chemokine.

  11. Cytotoxic and Inflammatory Responses Induced by Outer Membrane Vesicle-Associated Biologically Active Proteases from Vibrio cholerae

    Science.gov (United States)

    Mondal, Ayan; Tapader, Rima; Chatterjee, Nabendu Sekhar; Ghosh, Amit; Sinha, Ritam; Koley, Hemanta; Saha, Dhira Rani; Chakrabarti, Manoj K.; Wai, Sun Nyunt

    2016-01-01

    Proteases in Vibrio cholerae have been shown to play a role in its pathogenesis. V. cholerae secretes Zn-dependent hemagglutinin protease (HAP) and calcium-dependent trypsin-like serine protease (VesC) by using the type II secretion system (TIISS). Our present studies demonstrated that these proteases are also secreted in association with outer membrane vesicles (OMVs) and transported to human intestinal epithelial cells in an active form. OMV-associated HAP induces dose-dependent apoptosis in Int407 cells and an enterotoxic response in the mouse ileal loop (MIL) assay, whereas OMV-associated VesC showed a hemorrhagic fluid response in the MIL assay, necrosis in Int407 cells, and an increased interleukin-8 (IL-8) response in T84 cells, which were significantly reduced in OMVs from VesC mutant strain. Our results also showed that serine protease VesC plays a role in intestinal colonization of V. cholerae strains in adult mice. In conclusion, our study shows that V. cholerae OMVs secrete biologically active proteases which may play a role in cytotoxic and inflammatory responses. PMID:26930702

  12. In which preterm labor-patients is intravenous maintenance tocolysis effective?

    Science.gov (United States)

    Yoneda, Satoshi; Yoneda, Noriko; Fukuta, Kaori; Shima, Tomoko; Nakashima, Akitoshi; Shiozaki, Arihiro; Yoshino, Osamu; Kigawa, Mika; Yoshida, Taketoshi; Saito, Shigeru

    2018-03-01

    We evaluated whether maintenance tocolysis (intravenous ritodrine hydrochloride and/or magnesium sulfate) was effective in cases of spontaneous preterm labor with intact membranes. One hundred and thirty preterm labor patients who reached 36 weeks of gestation by maintenance tocolysis were selected. Immediate delivery (ID) after ceasing maintenance tocolysis was defined as an 'effective case'. The correlated factors between ID and no immediate delivery (NID) were statistically analyzed. Thirty-six patients delivered maintenance tocolysis (27.7%) and were defined as effective cases. Multiple logistic regression analysis revealed that amniotic fluid interleukin-8 at admission (≥ 2.3 ng/mL; odds ratio [OR] 5.6, 95% confidence interval [CI] 2.1-17.6; P Maintenance tocolysis may be effective in limited cases with mild intra-amniotic inflammation, in lean women and in cerclage cases. Maintenance tocolysis should be ceased in cases without these clinical factors when clinical symptoms disappear. © 2017 Japan Society of Obstetrics and Gynecology.

  13. Comparisons of IL-8, ROS and p53 responses in human lung epithelial cells exposed to two extracts of PM2.5 collected from an e-waste recycling area, China

    Energy Technology Data Exchange (ETDEWEB)

    Yang Fangxing [College of Environmental and Resource Sciences, Zhejiang University, Hangzhou (China); Jin Shiwei [Key Laboratory for Green Chemical Process of Ministry of Education, Wuhan Institute of Technology, Wuhan (China); Xu Ying; Lu Yuanan, E-mail: fxyang@ihb.ac.cn, E-mail: ylu@hawaii.edu [Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan (China)

    2011-04-15

    To identify the different effects of organic-soluble and water-soluble pollutants adsorbed on PM2.5 (PM: particulate matter) released from e-waste (electrical/electronic waste) on inflammatory response, oxidative stress and DNA damage, interleukin-8 (IL-8), reactive oxygen species (ROS) and p53 protein levels were determined and compared in human lung epithelial A549 cells exposed to extracts of PM2.5 collected from two sampling sites in an e-waste recycling area in China. It is found that both extracts induced increases of IL-8 release, ROS production and p53 protein expression. The differences between the organic-soluble and water-soluble extracts were determined as of significance for ROS production (p < 0.05) and p53 protein expression (p < 0.01). The ROS production and p53 protein expression induced by the organic-soluble extracts were found to be greater than those induced by the water-soluble extracts, for both sampling sites. The results indicated that PM2.5 collected from the e-waste recycling areas could lead to inflammatory response, oxidative stress and DNA damage, and the organic-soluble extracts had higher potential to induce such adverse effects on human health.

  14. A novel canine model of immune thrombocytopenia: Has ITP gone to the dogs?

    Science.gov (United States)

    LeVine, Dana N; Birkenheuer, Adam J; Brooks, Marjory B; Nordone, Shila K; Bellinger, Dwight A; Jones, Sam L; Fischer, Thomas H; Oglesbee, Stephen E; Frey, Kahlina; Brinson, Nicole S; Peters, Allison Pazandak; Marr, Henry S; Motsinger-Reif, Alison; Gudbrandsdottir, Sif; Bussel, James B; Key, Nigel S

    2014-01-01

    Summary Canine immune thrombocytopenia (ITP) is analogous to human ITP, with similar platelet counts and heterogeneity in bleeding phenotype among affected individuals. With a goal of ultimately investigating this bleeding heterogeneity, a canine model of antibody-mediated ITP was developed. Infusion of healthy dogs with 2F9, a murine IgG2a monoclonal antibody to the canine platelet glycoprotein GPIIb (a common target of autoantibodies in ITP) resulted in profound, dose-dependent thrombocytopenia. Model dogs developed variable bleeding phenotypes, e.g. petechiae and haematuria, despite similar degrees of thrombocytopenia. 2F9 infusion was not associated with systemic inflammation, consumptive coagulopathy, or impairment of platelet function. Unexpectedly however, evaluation of cytokine profiles led to the identification of platelets as a potential source of serum interleukin-8 (IL8) in dogs. This finding was confirmed in humans with ITP, suggesting that platelet IL8 may be a previously unrecognized modulator of platelet-neutrophil crosstalk. The utility of this model will allow future study of bleeding phenotypic heterogeneity including the role of neutrophils and endothelial cells in ITP. PMID:25039744

  15. Biological response of zebrafish embryos after short-term exposure to thifluzamide

    Science.gov (United States)

    Yang, Yang; Liu, Wenxian; Mu, Xiyan; Qi, Suzhen; Fu, Bin; Wang, Chengju

    2016-12-01

    Thifluzamide is a new amide fungicide, and its extensive application may have toxic effects on zebrafish. To better understand the underlying mechanism, we investigated in detail the potential toxic effects of thifluzamide on zebrafish embryos. In the present study, embryos were exposed to 0, 0.19, 1.90, and 2.85 mg/L thifluzamide for 4 days. Obvious pathological changes were found upon a histological exam, and negative changes in mitochondrial structure were observed under Transmission Electron Microscopy (TEM), which qualitatively noted the toxic effects of thifluzamide on embryos. Moreover, we quantitatively evaluated the enzyme activities [succinate dehydrogenase (SDH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), caspases], the contents of malonaldehyde (MDA) and interleukin-8 (IL-8) and the expression levels of the related genes. This study suggests that the negative changes in mitochondrial structure and SDH activity might be responsible for oxidative damage, cell apoptosis and inflammation, which would facilitate the action of these factors in cell death and might play a crucial role during toxic events. In addition to providing the first description of the mechanism of the toxic effects of thifluzamide on embryos, this study also represents a step towards using embryos to assess mitochondrial metabolism and disease.

  16. Dietary intake, lung function and airway inflammation in Mexico City school children exposed to air pollutants

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    Díaz-Sánchez David

    2009-12-01

    Full Text Available Abstract Introduction Air pollutant exposure has been associated with an increase in inflammatory markers and a decline in lung function in asthmatic children. Several studies suggest that dietary intake of fruits and vegetables might modify the adverse effect of air pollutants. Methods A total of 158 asthmatic children recruited at the Children's Hospital of Mexico and 50 non-asthmatic children were followed for 22 weeks. Pulmonary function was measured and nasal lavage collected and analyzed every 2 weeks. Dietary intake was evaluated using a 108-item food frequency questionnaire and a fruit and vegetable index (FVI and a Mediterranean diet index (MDI were constructed. The impact of these indices on lung function and interleukin-8 (IL-8 and their interaction with air pollutants were determined using mixed regression models with random intercept and random slope. Results FVI was inversely related to IL-8 levels in nasal lavage (p 1 (test for trend p 1 and FVC as was with MDI and ozone for FVC. No effect of diet was observed among healthy children. Conclusion Our results suggest that fruit and vegetable intake and close adherence to the Mediterranean diet have a beneficial effect on inflammatory response and lung function in asthmatic children living in Mexico City.

  17. Multiple pregnancy, short cervix, part-time worker, steroid use, low educational level and male fetus are risk factors for preterm birth in Japan: a multicenter, prospective study.

    Science.gov (United States)

    Shiozaki, Arihiro; Yoneda, Satoshi; Nakabayashi, Masao; Takeda, Yoshiharu; Takeda, Satoru; Sugimura, Motoi; Yoshida, Koyo; Tajima, Atsushi; Manabe, Mami; Akagi, Kozo; Nakagawa, Shoko; Tada, Katsuhiko; Imafuku, Noriaki; Ogawa, Masanobu; Mizunoe, Tomoya; Kanayama, Naohiro; Itoh, Hiroaki; Minoura, Shigeki; Ogino, Mitsuharu; Saito, Shigeru

    2014-01-01

    To examine the relationship between preterm birth and socioeconomic factors, past history, cervical length, cervical interleukin-8, bacterial vaginosis, underlying diseases, use of medication, employment status, sex of the fetus and multiple pregnancy. In a multicenter, prospective, observational study, 1810 Japanese women registering their future delivery were enrolled at 8⁺⁰ to 12⁺⁶ weeks of gestation. Data on cervical length and delivery were obtained from 1365 pregnant women. Multivariate logistic regression analysis was performed. Short cervical length, steroid use, multiple pregnancy and male fetus were risk factors for preterm birth before 34 weeks of gestation. Multiple pregnancy, low educational level, short cervical length and part-timer were risk factors for preterm birth before 37 weeks of gestation. Multiple pregnancy and cervical shortening at 20-24 weeks of gestation was a stronger risk factor for preterm birth. Any pregnant woman being part-time employee or low educational level, having a male fetus and requiring steroid treatment should be watched for the development of preterm birth. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  18. Campylobacter jejuni induces an anti-inflammatory response in human intestinal epithelial cells through activation of phosphatidylinositol 3-kinase/Akt pathway

    DEFF Research Database (Denmark)

    Li, Yiping; Vegge, Christina S.; Brøndsted, Lone

    2011-01-01

    to activate phosphatidylinositol 3-kinase (PI3K)/Akt pathway and induce pro-inflammatory interleukin-8(IL-8) as well as anti-inflammatory cytokine IL-10 in human intestinal epithelial cell line Colo 205. The signalling pathways PI3K/Akt and mitogen-activated protein (MAP)kinases ERK and p38 were involved in C....... jejuni-induced IL-8 and IL-10 expression. Inhibition of PI3K resulted in augmentation of C. jejuni-induced IL-8 production, concomitant with down-regulation of IL-10 mRNA, indicating an anti-inflammatory response was activated and associated with the activation of P13K/Akt. Similar effect was observed...... for cytolethal distending toxin (CDT) deficient mutants. Moreover, we demonstrated that heat-killed bacteria were able to induce IL-8 and IL-10 expression to a lower level than live bacteria. We therefore conclude that C. jejuni activate a PI3K/Akt-dependent anti-inflammatory pathway in human intestinal...

  19. β-Glucan induces reactive oxygen species production in human neutrophils to improve the killing of Candida albicans and Candida glabrata isolates from vulvovaginal candidiasis.

    Directory of Open Access Journals (Sweden)

    Patricia de Souza Bonfim-Mendonça

    Full Text Available Vulvovaginal candidiasis (VVC is among the most prevalent vaginal diseases. Candida albicans is still the most prevalent species associated with this pathology, however, the prevalence of other Candida species, such as C. glabrata, is increasing. The pathogenesis of these infections has been intensely studied, nevertheless, no consensus has been reached on the pathogenicity of VVC. In addition, inappropriate treatment or the presence of resistant strains can lead to RVVC (vulvovaginal candidiasis recurrent. Immunomodulation therapy studies have become increasingly promising, including with the β-glucans. Thus, in the present study, we evaluated microbicidal activity, phagocytosis, intracellular oxidant species production, oxygen consumption, myeloperoxidase (MPO activity, and the release of tumor necrosis factor α (TNF-α, interleukin-8 (IL-8, IL-1β, and IL-1Ra in neutrophils previously treated or not with β-glucan. In all of the assays, human neutrophils were challenged with C. albicans and C. glabrata isolated from vulvovaginal candidiasis. β-glucan significantly increased oxidant species production, suggesting that β-glucan may be an efficient immunomodulator that triggers an increase in the microbicidal response of neutrophils for both of the species isolated from vulvovaginal candidiasis. The effects of β-glucan appeared to be mainly related to the activation of reactive oxygen species and modulation of cytokine release.

  20. Long-term changes of serum chemokine levels in vaccinated military personnel

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    Brichacek Beda

    2006-09-01

    Full Text Available Abstract Background Members of the United States Armed Forces receive a series of vaccinations during their course of service. To investigate the influence of multiple vaccinations on innate immunity, we measured concentrations of a panel of immunomodulatory and pro-inflammatory cytokines in serum samples from a group of such individuals. Results Significantly increased levels of macrophage inflammatory protein 1α (MIP-1α, MIP-1β and interleukin 8 (IL-8 were detected. Since these cytokines are known to have anti-human immunodeficiency virus (HIV activity, we tested the effect of serum from these individuals on HIV-1 infectivity and susceptibility of their peripheral blood mononuclear cells (PBMCs to HIV-1 infection in vitro. Sera from vaccinated military personnel inhibited, and their PBMCs were partially resistant to, infection by HIV-1 strains tropic to CCR5 (R5, but not to CXCR4 (X4, chemokine receptor. Conclusion These findings demonstrate that increased anti-HIV chemokines can be detected in vaccine recipients up to 68 weeks following immunization.

  1. An Immunosuppressant Peptide from the Hard Tick Amblyomma variegatum

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    Yufeng Tian

    2016-05-01

    Full Text Available Ixodid ticks are well known for spreading transmitted tick-borne pathogens while being attached to their hosts for almost 1–2 weeks to obtain blood meals. Thus, they must secrete many immunosuppressant factors to combat the hosts’ immune system. In the present work, we investigated an immunosuppressant peptide of the hard tick Amblyomma variegatum. This peptide, named amregulin, is composed of 40 residues with an amino acid sequence of HLHMHGNGATQVFKPRLVLKCPNAAQLIQPGKLQRQLLLQ. A cDNA of the precursor peptide was obtained from the National Center for Biotechnology Information (NCBI, Bethesda, MD, USA. In rat splenocytes, amregulin exerts significant anti-inflammatory effects by inhibiting the secretion of inflammatory factors in vitro, such as tumor necrosis factor-alpha (TNF-α, interleukin-1 (IL-1, interleukin-8 (IL-8 and interferon-gamma (IFN-γ. In rat splenocytes, treated with amregulin, compared to lipopolysaccharide (LPS alone, the inhibition of the above inflammatory factors was significant at all tested concentrations (2, 4 and 8 µg/mL. Amregulin shows strong free radical scavenging and antioxidant activities (5, 10 and 20 µg/mL in vitro. Amregulin also significantly inhibits adjuvant-induced paw inflammation in mouse models in vivo. This peptide may facilitate the ticks’ successful blood feeding and may lead to host immunotolerance of the tick. These findings have important implications for the understanding of tick-host interactions and the co-evolution between ticks and the viruses that they bear.

  2. Eicosanoids in asthma.

    Science.gov (United States)

    Wan, Kong-Sang; Wu, Wei-Fong

    2007-01-01

    Eicosanoids belong to a diverse family of bioactive fatty acids that play important roles in regulating airway inflammation and reactivity. They are the key mediators of the pathobiology of asthma. Among the eicosanoids, lipoxins (LXs) were the first agents to be identified and recognized as potential anti-inflammatory endogenous lipid mediators. Lipoxins are biosynthesized in vivo at inflammation sites. They result mainly from the interaction between 5 and 15-lipoxygenases (LOs), which are distinct from leukotrienes (LTs) and prostaglandins (PGs) in structure and function. Leukotrienes are potent proinflammatory mediators and directly and indirectly stimulate fibroblast chemotaxis, proliferation, and collagen synthesis. Prostaglandins have both bronchoconstrictive and bronchoprotective effects and the bronchoconstriction mediated by PGD2 and PGF2alpha is only occurred in asthmatic patients but not in healthy subjects. Lipoxins counter-regulate the proinflammatory actions of LTs and activate resolution of the inflammatory response. At least two classes of receptors, CysLT1 receptors and Asprin-triggered lipoxin A4 (ALX) receptors, can interact with lipoxin A4 (LXA4) and LXA4 analogs to mediate their biologic actions. Allergen challenge initiates airway biosynthesis of LXA4 and increases expression of its receptor. In addition, LXA4 affects the release of interleukin-8 by blood mononuclear cells, and ALX affects calcium influx into epithelial cells. Therefore, the pivotal role of LXs is mediating airway homeostasis, and LXs may be part of a novel, multipronged approach for treating human asthma.

  3. Kidney injury and alterations of inflammatory cytokine expressions in mice following long-term exposure to cerium chloride.

    Science.gov (United States)

    Sang, Xuezi; Ze, Xiao; Gui, Suxin; Wang, Xiaochun; Hong, Jie; Ze, Yuguan; Zhao, Xiaoyang; Sheng, Lei; Sun, Qingqing; Yu, Xiaohong; Wang, Ling; Hong, Fashui

    2014-12-01

    It has been demonstrated that the organic damages of animals can be caused by exposure to lanthanide oxides or compounds. However, the molecular mechanism of CeCl3 -induced kidney injury remains unclear. In this study, the mechanism of nephric damage in mice induced by an intragastric administration of CeCl3 was investigated. The results showed that Ce(3+) was accumulated in the kidney, which in turn led to oxidative stress, severe nephric inflammation, and dysfunction in mice. Furthermore, CeCl3 activated nucleic factor κB, which in turn increased the expression levels of tumor necrosis factor α, macrophage migration inhibitory factor, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-18, interleukin-1β, cross-reaction protein, transforming growth factor-β, interferon-γ, and CYP1A1, while suppressed heat shock protein 70 expression. These findings implied that Ce(3+) -induced kidney injury of mice might be associated with oxidative stress, alteration of inflammatory cytokine expression, and reduction of detoxification of CeCl3 . © 2013 Wiley Periodicals, Inc.

  4. Solute removal capacity of high cut-off membrane plasma separators.

    Science.gov (United States)

    Ohkubo, Atsushi; Kurashima, Naoki; Nakamura, Ayako; Miyamoto, Satoko; Iimori, Soichiro; Rai, Tatemitsu

    2013-10-01

    In vitro blood filtration was performed by a closed circuit using high cut-off membrane plasma separators, EVACURE EC-2A10 (EC-2A) and EVACURE EC-4A10 (EC-4A). Samples were obtained from sampling sites before the plasma separator, after each plasma separator, and from the ultrafiltrate of each separator. The sieving coefficient (S.C.) of total protein (TP), albumin (Alb), IgG, interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), fibrinogen (Fib), antithrombin III (AT-III), and coagulation factor XIII (FXIII) were calculated. The S.C. of each solute using EC-2A and EC-A4 were as follows; TP: 0.25 and 0.56, Alb: 0.32 and 0.73, IgG: 0.16 and 0.50, IL-6:0.73 and 0.95, IL-8:0.85 and 0.82, TNF-α: 1.07 and 0.99, Fib: 0 and 0, FXIII: 0.07 and 0.17, respectively. When compared with the conventional type of membrane plasma separators, EVACURE could efficiently remove cytokines while retaining coagulation factors such as fibrinogen. Moreover, EC-2A prevented protein loss, whereas EC-4A could remove approximately 50% of IgG. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

  5. Serratia marcescens is injurious to intestinal epithelial cells.

    Science.gov (United States)

    Ochieng, John B; Boisen, Nadia; Lindsay, Brianna; Santiago, Araceli; Ouma, Collins; Ombok, Maurice; Fields, Barry; Stine, O Colin; Nataro, James P

    2014-01-01

    Diarrhea causes substantial morbidity and mortality in children in low-income countries. Although numerous pathogens cause diarrhea, the etiology of many episodes remains unknown. Serratia marcescens is incriminated in hospital-associated infections, and HIV/AIDS associated diarrhea. We have recently found that Serratia spp. may be found more commonly in the stools of patients with diarrhea than in asymptomatic control children. We therefore investigated the possible enteric pathogenicity of S. marcescens in vitro employing a polarized human colonic epithelial cell (T84) monolayer. Infected monolayers were assayed for bacterial invasion, transepithelial electrical resistance (TEER), cytotoxicity, interleukin-8 (IL-8) release and morphological changes by scanning electron microscopy. We observed significantly greater epithelial cell invasion by S. marcescens compared to Escherichia coli strain HS (p = 0.0038 respectively). Cell invasion was accompanied by reduction in TEER and secretion of IL-8. Lactate dehydrogenase (LDH) extracellular concentration rapidly increased within a few hours of exposure of the monolayer to S. marcescens. Scanning electron microscopy of S. marcescens-infected monolayers demonstrated destruction of microvilli and vacuolization. Our results suggest that S. marcescens interacts with intestinal epithelial cells in culture and induces dramatic alterations similar to those produced by known enteric pathogens.

  6. Why dapsone stops seizures and may stop neutrophils' delivery of VEGF to glioblastoma.

    Science.gov (United States)

    Kast, R E; Lefranc, F; Karpel-Massler, G; Halatsch, M-E

    2012-12-01

    Lopez-Gomez et al. recently published remarkable but mechanistically unexplained empirical evidence that the old antibiotic dapsone has antiepileptic activity. We addressed the question "Why should a sulfone antibiotic reduce seizures?". We report here our conclusions based on data from past studies that seizures are associated with elevated interleukin-8 (IL-8) and that dapsone inhibits IL-8 release and function in several different clinical and experimental contexts. Diverse CNS insults cause an increase in CNS IL-8. Thus, the pro-inflammatory environment generated by increase IL-8 leads to a lower seizure threshold. Together this evidence indicates dapsone exerts anti-seizure activity by diminishing IL-8 signalling. Since IL-8 is clearly upregulated in glioblastoma and contributes to the florid angiogenesis of that disease, and since interference with IL-8 function has been shown to inhibit glioblastoma invasion and growth in several experimental models, and dapsone has been repeatedly been shown to clinically inhibit IL-8 function when used to treat human neutrophilic dermatoses, we believe that dapsone thereby reduces seizures by countering IL-8 function and may similarly retard glioblastoma growth by such anti-IL-8 function.

  7. High-Throughput Screening Platform for the Discovery of New Immunomodulator Molecules from Natural Product Extract Libraries.

    Science.gov (United States)

    Pérez Del Palacio, José; Díaz, Caridad; de la Cruz, Mercedes; Annang, Frederick; Martín, Jesús; Pérez-Victoria, Ignacio; González-Menéndez, Víctor; de Pedro, Nuria; Tormo, José R; Algieri, Francesca; Rodriguez-Nogales, Alba; Rodríguez-Cabezas, M Elena; Reyes, Fernando; Genilloud, Olga; Vicente, Francisca; Gálvez, Julio

    2016-07-01

    It is widely accepted that central nervous system inflammation and systemic inflammation play a significant role in the progression of chronic neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, neurotropic viral infections, stroke, paraneoplastic disorders, traumatic brain injury, and multiple sclerosis. Therefore, it seems reasonable to propose that the use of anti-inflammatory drugs might diminish the cumulative effects of inflammation. Indeed, some epidemiological studies suggest that sustained use of anti-inflammatory drugs may prevent or slow down the progression of neurodegenerative diseases. However, the anti-inflammatory drugs and biologics used clinically have the disadvantage of causing side effects and a high cost of treatment. Alternatively, natural products offer great potential for the identification and development of bioactive lead compounds into drugs for treating inflammatory diseases with an improved safety profile. In this work, we present a validated high-throughput screening approach in 96-well plate format for the discovery of new molecules with anti-inflammatory/immunomodulatory activity. The in vitro models are based on the quantitation of nitrite levels in RAW264.7 murine macrophages and interleukin-8 in Caco-2 cells. We have used this platform in a pilot project to screen a subset of 5976 noncytotoxic crude microbial extracts from the MEDINA microbial natural product collection. To our knowledge, this is the first report on an high-throughput screening of microbial natural product extracts for the discovery of immunomodulators. © 2016 Society for Laboratory Automation and Screening.

  8. Calreticulin Release at an Early Stage of Death Modulates the Clearance by Macrophages of Apoptotic Cells

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    Rim Osman

    2017-08-01

    Full Text Available Calreticulin (CRT is a well-known “eat-me” signal harbored by dying cells participating in their recognition by phagocytes. CRT is also recognized to deeply impact the immune response to altered self-cells. In this study, we focus on the role of the newly exposed CRT following cell death induction. We show that if CRT increases at the outer face of the plasma membrane and is well recognized by C1q even when phosphatidylserine is not yet detected, CRT is also released in the surrounding milieu and is able to interact with phagocytes. We observed that exogenous CRT is endocytosed by THP1 macrophages through macropinocytosis and that internalization is associated with a particular phenotype characterized by an increase of cell spreading and migration, an upregulation of CD14, an increase of interleukin-8 release, and a decrease of early apoptotic cell uptake. Importantly, CRT-induced pro-inflammatory phenotype was confirmed on human monocytes-derived macrophages by the overexpression of CD40 and CD274, and we found that monocyte-derived macrophages exposed to CRT display a peculiar polarization notably associated with a downregulation of the histocompatibility complex of class II molecules hampering its description through the classical M1/M2 dichotomy. Altogether our results highlight the role of soluble CRT with strong possible consequences on the macrophage-mediated immune response to dying cell.

  9. Calreticulin Release at an Early Stage of Death Modulates the Clearance by Macrophages of Apoptotic Cells

    Science.gov (United States)

    Osman, Rim; Tacnet-Delorme, Pascale; Kleman, Jean-Philippe; Millet, Arnaud; Frachet, Philippe

    2017-01-01

    Calreticulin (CRT) is a well-known “eat-me” signal harbored by dying cells participating in their recognition by phagocytes. CRT is also recognized to deeply impact the immune response to altered self-cells. In this study, we focus on the role of the newly exposed CRT following cell death induction. We show that if CRT increases at the outer face of the plasma membrane and is well recognized by C1q even when phosphatidylserine is not yet detected, CRT is also released in the surrounding milieu and is able to interact with phagocytes. We observed that exogenous CRT is endocytosed by THP1 macrophages through macropinocytosis and that internalization is associated with a particular phenotype characterized by an increase of cell spreading and migration, an upregulation of CD14, an increase of interleukin-8 release, and a decrease of early apoptotic cell uptake. Importantly, CRT-induced pro-inflammatory phenotype was confirmed on human monocytes-derived macrophages by the overexpression of CD40 and CD274, and we found that monocyte-derived macrophages exposed to CRT display a peculiar polarization notably associated with a downregulation of the histocompatibility complex of class II molecules hampering its description through the classical M1/M2 dichotomy. Altogether our results highlight the role of soluble CRT with strong possible consequences on the macrophage-mediated immune response to dying cell. PMID:28878781

  10. Sulfur mustard vapor effects on differentiated human lung cells

    Science.gov (United States)

    Seagrave, JeanClare; Weber, Waylon M.; Grotendorst, Gary R.

    2011-01-01

    Context sulfur mustard (SM) causes skin blistering and long-term pulmonary dysfunction. Its adverse effects have been studied in battlefield-exposed humans, but lack of knowledge regarding confounding factors makes interpretation challenging. Animal studies are critical to understanding mechanisms, but differences between animals and humans must be addressed. Studies of cultured human cells can bridge animal studies and humans. Objective Evaluate effects of SM vapor on airway cells. Materials and methods We examined responses of differentiated human tracheal/bronchial epithelial cells, cultured at an air-liquid interface, to SM vapors. SM effects on metabolic activity (Water Soluble Tetrazolium (WST) assay), cytokine and metalloproteinase secretion, and cellular heme oxygenase 1 (HO-1), an oxidative stress indicator, were measured after 24 h. Results At noncytotoxic levels of exposure, interleukin 8 and matrix metalloproteinase-13 were significantly increased in these cultures, but HO-1 was not significantly affected. Discussion and conclusion Exposure of differentiated airway epithelial cells to sub-cytotoxic levels of SM vapor induced inflammatory and degradative responses that could contribute to the adverse health effects of inhaled SM. PMID:20569120

  11. Respiratory epithelial cells require Toll-like receptor 4 for induction of Human β-defensin 2 by Lipopolysaccharide

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    McElvaney Noel

    2005-10-01

    Full Text Available Abstract Background The respiratory epithelium is a major portal of entry for pathogens and employs innate defense mechanisms to prevent colonization and infection. Induced expression of human β-defensin 2 (HBD2 represents a direct response by the epithelium to potential infection. Here we provide evidence for the critical role of Toll-like receptor 4 (TLR4 in lipopolysaccharide (LPS-induced HBD2 expression by human A549 epithelial cells. Methods Using RTPCR, fluorescence microscopy, ELISA and luciferase reporter gene assays we quantified interleukin-8, TLR4 and HBD2 expression in unstimulated or agonist-treated A549 and/or HEK293 cells. We also assessed the effect of over expressing wild type and/or mutant TLR4, MyD88 and/or Mal transgenes on LPS-induced HBD2 expression in these cells. Results We demonstrate that A549 cells express TLR4 on their surface and respond directly to Pseudomonas LPS with increased HBD2 gene and protein expression. These effects are blocked by a TLR4 neutralizing antibody or functionally inactive TLR4, MyD88 and/or Mal transgenes. We further implicate TLR4 in LPS-induced HBD2 production by demonstrating HBD2 expression in LPS non-responsive HEK293 cells transfected with a TLR4 expression plasmid. Conclusion This data defines an additional role for TLR4 in the host defense in the lung.

  12. Balneotherapy of Psoriasis

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    Golušin Zoran

    2014-09-01

    Full Text Available Application of different kinds of mineral waters and peloids on the skin exerts mechanical, thermal and chemical effects. Significant reduction of inflammation and increased differentiation of keratinocytes may explain why balneotherapy has positive clinical effects in psoriatic patients. In vitro models have shown that thermal water stimulates interleukin-2 production after cell stimulation by staphylococcal enterotoxin B, and reduces interleukin-4 secretion. After balneotherapy, a significant decrease in Psoriasis Area Severity Index (PASI, associated with a significant reduction of interleukin-8, Staphylococcus aureus colonization and enterotoxin N, have been reported in patients with psoriasis. Mineral water was found to have inhibitory in vitro effects on substance P, TNF-α release and antigen-induced cell degranulation. Immunomodulatory effects of water depend on its content. Sulfur waters have beneficial anti-inflammatory, keratolytic, and antipruriginous effects and also possess antibacterial and antifungal properties. The effectiveness of balneotherapy in the treatment of psoriasis has been reported in many studies conducted all over the world. The majority of studies were conducted at the Dead Sea coast. Investigations showed that balneotherapy factors are important therapeutic factors in the treatment of psoriatic patients. The first and only comparable study of this kind in Serbia, was conducted in Prolom Spa with satisfactory therapeutic results.

  13. The role of adipose-derived stem cells in a self-organizing 3D model with regard to human soft tissue healing.

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    Oberringer, Martin; Bubel, Monika; Jennewein, Martina; Guthörl, Silke; Morsch, Tamara; Bachmann, Sophie; Metzger, Wolfgang; Pohlemann, Tim

    2018-01-05

    The clinical phenomenon of inadequate soft tissue healing still remains an important issue. The occurrence of chronic wounds is correlated to the life span, which is still increasing in western countries. Tissue engineering products containing adipose-derived stem cells are discussed as a promising therapeutic approach. Several studies confirmed the value of these cells for soft tissue healing improvement, suggesting a paracrine as well as a direct effect on vessel repair and angiogenesis. In an attempt to figure out specific effects of adipose-derived stem cells on dermal microvascular endothelial cells with respect to the different phases of soft tissue healing, we designed a 3D in vitro model on the basis of spheroids. Basic parameters like spheroid volume, cell numbers, and rate of apoptotic cells were determined in dependence on culture time, on different oxygen conditions and using mono- as well as co-cultures of both cell types. Furthermore we focused on gene expression and protein levels of interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor, which are discussed against the background of therapies for chronic wounds. The visualization of α-smooth muscle actin allowed the estimation of the function of adipose-derived stem cells as stabilizer for dermal microvascular endothelial cells. The results of the present 3D model underscore a paracrine effect of adipose-derived stem cells on microvessel repair during early hypoxic conditions, whereas a stabilizing effect occurs during a later phase of soft tissue healing, simultaneously to reoxygenation.

  14. ROLE OF THE KNOWN MUCOLYTICS IN MUCOVISCIDOSIS THERAPY

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    O. I. Simonova

    2014-01-01

    Full Text Available The primary objective in the mucoviscidosis therapy is to ensure normal rheology of respiratory secretion for effective evacuationthereof from the bronchial tree and nasal sinuses. Enzyme drug dornase alfa features the best evidence base for effectiveness and safety of use to treat mucoviscidosis among mucolytics; it rapidly transforms thick viscous sputum into liquid secretion. Along with that, numerous studies have confirmed anti-inflammatory and antibacterial effects thereof: the enzyme breaks down biofilm of the mucoid Pseudomonas aeruginosa, thus reducing volume of the destructive component in pulmonary tissue in the event of an inflammation; it is capable of decreasing concentration of neutrophil elastase and interleukin 8 in sputum, as well as of matrix metal proteinases in bronchoalveolar lavage. Continuous intake of this drug in combination with kinesitherapy and other baseline drugs ensures the patient’s well-being, lower rate of bronchopulmonary process exacerbations, reduction in the hospital admission rate and significant improvement of the quality of life. 

  15. Soluble Fibre Meal Challenge Reduces Airway Inflammation and Expression of GPR43 and GPR41 in Asthma

    Directory of Open Access Journals (Sweden)

    Isabel Halnes

    2017-01-01

    Full Text Available Short chain fatty acids (SCFAs are produced following the fermentation of soluble fibre by gut bacteria. In animal models, both dietary fibre and SCFAs have demonstrated anti-inflammatory effects via the activation of free fatty acid receptors, such as G protein-coupled receptor 41 and 43 (GPR41 and GPR43. This pilot study examined the acute effect of a single dose of soluble fibre on airway inflammation—including changes in gene expression of free fatty acid receptors—in asthma. Adults with stable asthma consumed a soluble fibre meal (n = 17 containing 3.5 g inulin and probiotics, or a control meal (n = 12 of simple carbohydrates. Exhaled nitric oxide (eNO was measured and induced sputum was collected at 0 and 4 h for differential cell counts, measurement of interleukin-8 (IL-8 protein concentration, and GPR41 and GPR43 gene expression. At 4 h after meal consumption, airway inflammation biomarkers, including sputum total cell count, neutrophils, macrophages, lymphocytes, sputum IL-8, and eNO significantly decreased compared to baseline in the soluble fibre group only. This corresponded with upregulated GPR41 and GPR43 sputum gene expression and improved lung function in the soluble fibre group alone. Soluble fibre has acute anti-inflammatory effects in asthmatic airways. Long-term effects of soluble fibre as an anti-inflammatory therapy in asthma warrants further investigation.

  16. The changes and significance of serum inflammatory factors and hemodynamics in patients with acute cerebral infarction

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    Xiao-Wei Lu

    2016-01-01

    Full Text Available Objective: To investigate the changes of serum inflammatory factors and hemodynamics in patients with acute cerebral infarction and its clinical significance. Methods: A total of 55 cases of acute cerebral infarction (ACI patients as observation group, and cases of healthy physical examination were selected as the observation group, and 55 healthy persons as control group. ELISA method was used to detect inflammatory cytokines interleukin-6 (IL-6, interleukin-8 (IL-8, C-reactive protein (CRP and tumor necrosis factor (TNF-α level, WA- 880 heart and brain integrated digital hemodynamic monitor to detect bilateral carotid artery blood flow velocity, blood flow and peripheral resistance. Results: The serum levels of IL-8, CRP, IL-6 and TNF-α were higher in the observation group than in the control group, the difference was statistically significant (P<0.05. The blood flow velocity and blood flow velocity in the observation group were significantly lower than those in the control group. The difference was statistically significant (IL-8. With the increase of infarct size, serum IL-6, CRP, P<0.05 and TNF-α increased significantly (P<0.05. Conclusions: The changes of serum inflammatory factors and hemodynamic indexes can be used to judge the early cerebral infarction and the size of the infarct size of the index, the clinical dynamic monitoring of its changes in patients with acute cerebral infarction and the severity of the prognosis and the prognosis of the important significance of the judgment.

  17. Determinants of the postpericardiotomy syndrome: a systematic review.

    Science.gov (United States)

    van Osch, Dirk; Nathoe, Hendrik M; Jacob, Kirolos A; Doevendans, Pieter A; van Dijk, Diederik; Suyker, Willem J; Dieleman, Jan M

    2017-06-01

    Postpericardiotomy syndrome (PPS) is a common complication following cardiac surgery; however, the exact pathogenesis remains uncertain. Identifying risk factors of PPS might help to better understand the syndrome. The aim of this study was to provide an overview of existing literature around determinants of PPS in adult cardiac surgery patients. Two independent investigators performed a systematic search in MEDLINE, EMBASE and the Cochrane Central Register. The search aimed to identify studies published between January 1950 and December 2015, in which determinants of PPS were reported. A total of 19 studies met the selection criteria. In these studies, 14 different definitions of PPS were used. The median incidence of PPS was 16%. After quality assessment, seven studies were considered eligible for this review. Lower preoperative interleukin-8 levels and higher postoperative complement conversion products were associated with a higher risk of PPS. Among other clinical factors, a lower age, transfusion of red blood cells and lower preoperative platelet and haemoglobin levels were associated with a higher risk of PPS. Colchicine use decreased the risk of PPS. We found that both the inflammatory response and perioperative bleeding and coagulation may play a role in the development of PPS, suggesting a multifactorial aetiology of the syndrome. Due to a lack of a uniform definition of PPS in the past, study comparability was poor across the studies. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  18. Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations

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    Ludovica Ciuffreda

    2009-08-01

    Full Text Available The Raf/MEK/ERK pathway is an importantmediator of tumor cell proliferation and angiogenesis. Here, weinvestigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC50 in the nanomolar range even in the least responsive models. Growth inhibition was observed both in vitro and in vivo in xenograft models, regardless of BRAF mutation status, and was due to G1-phase cell cycle arrest and subsequent induction of apoptosis. Cell cycle (cyclin D1, c-Myc, and p27KIP1 and apoptosis (Bcl-2 and survivin regulators were modulated by PD0325901 at the protein level. Gene expression profiling revealed profound modulation of several genes involved in the negative control of MAPK signaling and melanoma cell differentiation, suggesting alternative, potentially relevant mechanisms of action. Finally, PD0325901 inhibited the production of the proangiogenic factors vascular endothelial growth factor and interleukin 8 at a transcriptional level. In conclusion, PD0325901 exerts potent growth-inhibitory, proapoptotic, and antiangiogenic activity in melanoma lines, regardless of their BRAF mutation status. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective treatment strategies for patients experiencing malignant melanoma.

  19. Phenolic-rich extract from the Costa Rican guava (Psidium friedrichsthalianum) pulp with antioxidant and anti-inflammatory activity. Potential for COPD therapy.

    Science.gov (United States)

    Flores, Gema; Dastmalchi, Keyvan; Wu, Shi-Biao; Whalen, Kathleen; Dabo, Abdoulaye J; Reynertson, Kurt A; Foronjy, Robert F; D Armiento, Jeanine M; Kennelly, Edward J

    2013-11-15

    The potential therapeutic effects of Costa Rican guava (Psidium friedrichsthalianum) extracts for chronic obstructive pulmonary disease were examined. The ethyl acetate fraction displayed the highest antioxidant activity, as compared to the hexane, chloroform, and n-butanol fractions, as well as the crude extract. This fraction was evaluated for its anti-inflammatory activity response relationship against interleukin-8 (IL-8) and inhibition of matrix metalloproteinase-1 (MMP-1) expression before and after treatment with cigarette smoke. The ethyl acetate fraction exhibited inhibitory activity against IL-8 production and MMP-1 expression, showing the most potent inhibitory activities in both assays at 100μg/mL, and nine compounds (1-9) were found. Phenolic compounds 1-O-trans-cinnamoyl-β-d-glucopyranose (2), ellagic acid (3), myricetin (4), quercitrin (7), and quercetin (9) were identified using standard compounds or literature reports from related species. Compounds 1, 5, 6, and 8 were tentatively identified as 1,5-dimethyl citrate (1), sinapic aldehyde 4-O-β-d-glucopyranose (5), 3,3',4-tri-O-methylellagic acid-4'-O-d-glucopyranoside (6), and 1,3-O-diferuloylglycerol (8), All nine compounds are reported for the first time in Costa Rican guava. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Immunomodulatory properties of fermented soy and dairy milks prepared with lactic acid bacteria.

    Science.gov (United States)

    Wagar, L E; Champagne, C P; Buckley, N D; Raymond, Y; Green-Johnson, J M

    2009-10-01

    Fermented soy and dairy milk preparations provide a means for delivering lactic acid bacteria and their fermentation products into the diet. Our aims were to test immunomodulatory bioactivity of fermented soy beverage (SB) and dairy milk blend (MB) preparations on human intestinal epithelial cells (IEC) and to determine the impact of freezing medium on culture survival prior to bioactivity analyses. Fermented SB and MB were prepared using pure or mixed cultures of Streptococcus thermophilus ST5, Bifidobacterium longum R0175, and Lactobacillus helveticus R0052. Immunomodulatory bioactivity was assessed by testing selected SB and MB ferments on tumor necrosis factor alpha (TNFalpha)-treated IEC and measuring effects on Interleukin-8 (IL-8) production. Impact of timing of ferment administration relative to this pro-inflammatory challenge was investigated. The most pronounced reductions in IEC IL-8 production were observed when IEC were treated with either SB or MB ferment preparations prior to TNFalpha challenge. These results indicate that freezing-stable MB and SB ferments prepared with selected strains can modulate IEC IL-8 production in vitro, and suggest that yogurt-like fermented soy formulations could provide a functional food alternative to milk-based fermented products.

  1. Benefits of whole body vibration training in patients hospitalised for COPD exacerbations - a randomized clinical trial.

    Science.gov (United States)

    Greulich, Timm; Nell, Christoph; Koepke, Janine; Fechtel, Juliane; Franke, Maja; Schmeck, Bernd; Haid, Daniel; Apelt, Sandra; Filipovic, Silke; Kenn, Klaus; Janciauskiene, Sabina; Vogelmeier, Claus; Koczulla, Andreas Rembert

    2014-04-11

    Patients with stable COPD show improvements in exercise capacity and muscular function after the application of whole body vibration. We aimed to evaluate whether this modality added to conventional physiotherapy in exacerbated hospitalised COPD patients would be safe and would improve exercise capacity and quality of life. 49 hospitalised exacerbated COPD patients were randomized (1:1) to undergo physiotherapy alone or physiotherapy with the addition of whole body vibration. The primary endpoint was the between-group difference of the 6-minute walking test (day of discharge - day of admission). Secondary assessments included chair rising test, quality of life, and serum marker analysis. Whole body vibration did not cause procedure-related adverse events. Compared to physiotherapy alone, it led to significantly stronger improvements in 6-minute walking test (95.55 ± 76.29 m vs. 6.13 ± 81.65 m; p = 0.007) and St. Georges Respiratory Questionnaire (-6.43 ± 14.25 vs. 5.59 ± 19.15, p = 0.049). Whole body vibration increased the expression of the transcription factor peroxisome proliferator receptor gamma coactivator-1-α and serum levels of irisin, while it decreased serum interleukin-8. Whole body vibration during hospitalised exacerbations did not cause procedure-related adverse events and induced clinically significant benefits regarding exercise capacity and health-related quality of life that were associated with increased serum levels of irisin, a marker of muscle activity. German Clinical Trials Register DRKS00005979. Registered 17 March 2014.

  2. Subversion of autophagy in adherent invasive Escherichia coli-infected neutrophils induces inflammation and cell death.

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    Abderrahman Chargui

    Full Text Available Invading bacteria are recognized, captured and killed by a specialized form of autophagy, called xenophagy. Recently, defects in xenophagy in Crohn's disease (CD have been implicated in the pathogenesis of human chronic inflammatory diseases of uncertain etiology of the gastrointestinal tract. We show here that pathogenic adherent-invasive Escherichia coli (AIEC isolated from CD patients are able to adhere and invade neutrophils, which represent the first line of defense against bacteria. Of particular interest, AIEC infection of neutrophil-like PLB-985 cells blocked autophagy at the autolysosomal step, which allowed intracellular survival of bacteria and exacerbated interleukin-8 (IL-8 production. Interestingly, this block in autophagy correlated with the induction of autophagic cell death. Likewise, stimulation of autophagy by nutrient starvation or rapamycin treatment reduced intracellular AIEC survival and IL-8 production. Finally, treatment with an inhibitor of autophagy decreased cell death of AIEC-infected neutrophil-like PLB-985 cells. In conclusion, excessive autophagy in AIEC infection triggered cell death of neutrophils.

  3. Reverse pharmacognosy: application of selnergy, a new tool for lead discovery. The example of epsilon-viniferin.

    Science.gov (United States)

    Do, Quoc-Tuan; Renimel, Isabelle; Andre, Patrice; Lugnier, Claire; Muller, Christian D; Bernard, Philippe

    2005-09-01

    The aim of reverse pharmacognosy is to find new biological targets for natural compounds by virtual or real screening and identify natural resources that contain the active molecules. To demonstrate the applicability of this concept, we report here a study on epsilon-viniferin, an active ingredient for cosmetic development. Nevertheless, this natural substance is weakly defined in terms of biological properties. SELNERGY, an inverse docking computer software, was used to identify putative binding biological targets for epsilon-viniferin. Among the 400 screened proteins two targets were retained. For cosmetic application, cyclic nucleotide phosphodiesterase 4 (PDE4) was the most interesting candidate. Moreover, other PDE subtypes (1, 2, 3, 5 and 6) were not retained, indicating a selectivity for PDE4. The experimental binding tests on the 6 subtypes of PDE revealed a significant selectivity of epsilon-viniferin for the PDE4 subtype. This selectivity was confirmed by evaluation of epsilon-viniferin on the secretion of TNF-alpha and Interleukin-8. Our data demonstrated that epsilon-viniferin possesses anti-inflammatory properties by inhibiting PDE4 subtype. In conclusion, reverse pharmacognosy and its inverse docking component cannot only be integrated into a program for new lead discovery but is also a useful approach to find new applications for identified compounds.

  4. Endometriosis Leads to an Increased Trefoil Factor 3 Concentration in the Peritoneal Cavity but Does Not Alter Systemic Levels.

    Science.gov (United States)

    Henze, Diana; Doecke, Wolf-Dietrich; Hornung, Daniela; Agueusop, Inoncent; von Ahsen, Oliver; Machens, Kathrin; Schmitz, Arndt A; Gashaw, Isabella

    2017-02-01

    This study analyzed whether trefoil factor 3 (TFF3) is locally elevated and correlated with common biomarkers and inflammatory processes in endometriosis. Peritoneal fluid (PF) was obtained from 50 women and serum from 124 women with or without endometriosis. Experimental endometriosis was induced in female C57BL/6 mice by syngeneic transplantation of uterine tissue to the abdominal wall. Levels of TFF3 in PF of women with endometriosis were significantly increased ( P endometriosis: cancer antigen (CA) 125, CA-19-9, interleukin 8, monocyte chemotactic protein 1, and matrix metalloproteinase 7. Serum levels of TFF3 in women were significantly influenced by the menstrual cycle but were independent from disease state. In mice, local TFF3 levels were significantly elevated in early endometriosis (up to 4 weeks after transplantation, P peritoneal cavity in endometriosis and might play a role in disease pathogenesis and its associated inflammatory processes. Furthermore, the results show that TFF3 is regulated through the menstrual cycle. With respect to animal models, syngeneic mouse model does reflect local TFF3 upregulation in the peritoneal cavity affected by endometriosis.

  5. Dietary intake, lung function and airway inflammation in Mexico City school children exposed to air pollutants.

    Science.gov (United States)

    Romieu, Isabelle; Barraza-Villarreal, Albino; Escamilla-Núñez, Consuelo; Texcalac-Sangrador, Jose L; Hernandez-Cadena, Leticia; Díaz-Sánchez, David; De Batlle, Jordi; Del Rio-Navarro, Blanca E

    2009-12-10

    Air pollutant exposure has been associated with an increase in inflammatory markers and a decline in lung function in asthmatic children. Several studies suggest that dietary intake of fruits and vegetables might modify the adverse effect of air pollutants. A total of 158 asthmatic children recruited at the Children's Hospital of Mexico and 50 non-asthmatic children were followed for 22 weeks. Pulmonary function was measured and nasal lavage collected and analyzed every 2 weeks. Dietary intake was evaluated using a 108-item food frequency questionnaire and a fruit and vegetable index (FVI) and a Mediterranean diet index (MDI) were constructed. The impact of these indices on lung function and interleukin-8 (IL-8) and their interaction with air pollutants were determined using mixed regression models with random intercept and random slope. FVI was inversely related to IL-8 levels in nasal lavage (p diet was observed among healthy children. Our results suggest that fruit and vegetable intake and close adherence to the Mediterranean diet have a beneficial effect on inflammatory response and lung function in asthmatic children living in Mexico City.

  6. Sequencing and phylogenetic analysis of partial CXCR2 gene of Murrah buffalo

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    S. A. Wani

    2014-05-01

    Full Text Available Aim: Present study was carried out to sequence and phylogenetic analysis of CXCR2 gene of Murrah buffalo. Materials and Methods: For the present investigation, from a group of forty eight Murrah buffaloes (Bubalus bubalis, blood samples were collected randomly from eight animals, out of which four were healthy and four were mastitic. Results: The amplification of Interleukin-8B (IL-8B receptor gene target sequence was carried out using the primer pair in an optimized polymerase chain reaction. Partial sequencing of IL-8B receptor gene of Bubalus bubalis (Murrah has been done successfully. The sequences of IL-8B receptor gene showed 99% homology to that of Bos indicus × Bos taurus, 98% to that of Bos taurus, 97% to that of Ovis aries, 93% to that of Sus scrofa, 92% to that of Equus caballus and 90% to that of Felis catus. Conclusion: From the present study it can be concluded that the PCR amplification procedure for target region of IL-8B receptor gene yielding 459 bp products has been standardized, which yielded consistent and specific amplification. Amplification of partial IL-8B receptor gene (exon 2- 459 bp using self designed primers specific for cattle ortholog sequence signifies that the locus is conserved in cattle and buffaloes. In phylogenetic tree, the target sequence of IL-8B receptor gene of Bubalus bubalis were found to be more closely related to Bos indicus × Bos Taurus and Bos taurus than to Ovis aries and Sus scrofa.

  7. Antibacterial activity of the human host defence peptide LL-37 and selected synthetic cationic lipids against bacteria associated with oral and upper respiratory tract infections.

    Science.gov (United States)

    Leszczynska, Katarzyna; Namiot, Dorota; Byfield, Fitzroy J; Cruz, Katrina; Zendzian-Piotrowska, Malgorzata; Fein, David E; Savage, Paul B; Diamond, Scott; McCulloch, Christopher A; Janmey, Paul A; Bucki, Robert

    2013-03-01

    We aim to develop antibacterial peptide mimics resistant to protease degradation, with broad-spectrum activity at sites of infection. The bactericidal activities of LL-37, ceragenins CSA-13, CSA-90 and CSA-92 and the spermine-conjugated dexamethasone derivative D2S were evaluated using MIC and MBC measurements. Gingival fibroblast counting, interleukin-8 (IL-8) and lactate dehydrogenase (LDH) release from keratinocytes (HaCat) were used to determine effects on cell growth, pro-inflammatory response and toxicity. All tested cationic lipids showed stronger bactericidal activity than LL-37. Incubation of Staphylococcus aureus with half the MIC of LL-37 led to the appearance of bacteria resistant to its bactericidal effects, but identical incubations with CSA-13 or D2S did not produce resistant bacteria. Cathelicidin LL-37 significantly increased the total number of gingival fibroblasts, but ceragenins and D2S did not alter gingival fibroblast growth. Cationic lipids showed no toxicity to HaCat cells at concentrations resulting in bacterial killing. These data suggest that cationic lipids such as ceragenins warrant further testing as potential novel antibacterial agents.

  8. Soluble Fibre Meal Challenge Reduces Airway Inflammation and Expression of GPR43 and GPR41 in Asthma

    Science.gov (United States)

    Halnes, Isabel; Baines, Katherine J.; Berthon, Bronwyn S.; MacDonald-Wicks, Lesley K.; Gibson, Peter G.; Wood, Lisa G.

    2017-01-01

    Short chain fatty acids (SCFAs) are produced following the fermentation of soluble fibre by gut bacteria. In animal models, both dietary fibre and SCFAs have demonstrated anti-inflammatory effects via the activation of free fatty acid receptors, such as G protein-coupled receptor 41 and 43 (GPR41 and GPR43). This pilot study examined the acute effect of a single dose of soluble fibre on airway inflammation—including changes in gene expression of free fatty acid receptors—in asthma. Adults with stable asthma consumed a soluble fibre meal (n = 17) containing 3.5 g inulin and probiotics, or a control meal (n = 12) of simple carbohydrates. Exhaled nitric oxide (eNO) was measured and induced sputum was collected at 0 and 4 h for differential cell counts, measurement of interleukin-8 (IL-8) protein concentration, and GPR41 and GPR43 gene expression. At 4 h after meal consumption, airway inflammation biomarkers, including sputum total cell count, neutrophils, macrophages, lymphocytes, sputum IL-8, and eNO significantly decreased compared to baseline in the soluble fibre group only. This corresponded with upregulated GPR41 and GPR43 sputum gene expression and improved lung function in the soluble fibre group alone. Soluble fibre has acute anti-inflammatory effects in asthmatic airways. Long-term effects of soluble fibre as an anti-inflammatory therapy in asthma warrants further investigation. PMID:28075383

  9. Saussurea lappa alleviates inflammatory chemokine production in HaCaT cells and house dust mite-induced atopic-like dermatitis in Nc/Nga mice.

    Science.gov (United States)

    Lim, Hye-Sun; Ha, Hyekyung; Lee, Mee-Young; Jin, Seong-Eun; Jeong, Soo-Jin; Jeon, Woo-Young; Shin, Na-Ra; Sok, Dai-Eun; Shin, Hyeun-Kyoo

    2014-01-01

    Saussurea lappa is a traditional herbal medicine used for to treat various inflammatory diseases. In this study, we investigated the protective effects of S. lappa against atopic dermatitis using human keratinocyte HaCaT cells, murine mast cell line MC/9 cells, and a house dust mite-induced atopic dermatitis model of Nc/Nga mice. Treatment with the S. lappa caused a significant reduction in the mRNA levels and production of inflammatory chemokines and cytokine, including thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), regulated on activation, normal T-cell expressed and secreted (RANTES), and interleukin-8 (IL-8) in tumor necrosis factor-α/interferone-γ-stimulated HaCaT cells. S. lappa exhibited the significant reduction in histamine production in MC/9 cells. In the atopic dermatitis model, S. lappa significantly reduced the dermatitis score and serum IgE and TARC levels. In addition, the back skin and ears of S. lappa-treated Nc/Nga mice exhibited reduced histological manifestations of atopic skin lesions such as erosion, hyperplasia of the epidermis and dermis, and inflammatory cell infiltration. In conclusion, an extract of S. lappa effectively suppressed the development of atopic dermatitis, which was closely related to the reduction of chemokines and cytokine. Our study suggests that S. lappa may be a potential treatment for atopic dermatitis. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  10. Health Benefits of an Innovative Exercise Program for Mitochondrial Disorders.

    Science.gov (United States)

    Fiuza-Luces, Carmen; Díez-Bermejo, Jorge; Fernández-de la Torre, Miguel; Rodríguez-Romo, Gabriel; Sanz-Ayán, Paz; Delmiro, Aitor; Munguía-Izquierdo, Diego; Rodríguez-Gómez, Irene; Ara, Ignacio; Domínguez-González, Cristina; Arenas, Joaquín; Martín, Miguel A; Lucia, Alejandro; Morán, María

    2018-01-08

    We determined the effects of an innovative 8-week exercise intervention (aerobic, resistance and inspiratory muscle training) for patients with mitochondrial disease (MD). Several endpoints were assessed in 12 patients (19-59 years, 4 female) at pre-training, post-training and after 4-week detraining: aerobic power, muscle strength/power and maximal inspiratory pressure (main endpoints), ability to perform activities of daily living (ADL), body composition, quality of life and blood myokines (secondary endpoints). The program was safe with patients' adherence being 94±5%. A significant time-effect was found for virtually all main endpoints (P≤0.004), indicating a training improvement. Similar findings (P≤0.003) were found for ADL tests, total/trunk/leg lean mass, total fat mass, femoral fracture risk and general health perception. No differences were found for blood myokines, except for an acute exertional increase in interleukin-8 at post-training/detraining (P=0.002) and in fatty acid binding protein 3 at detraining (P=0.002). An intervention including novel exercises for MD patients (e.g., inspiratory muscle training) produced benefits in numerous indicators of physical capacity, and induced a previously unreported shift towards a healthier body composition phenotype.

  11. Autocrine signaling is a key regulatory element during osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Paul Kopesky

    2014-07-01

    Full Text Available Osteoclasts are responsible for bone destruction in degenerative, inflammatory and metastatic bone disorders. Although osteoclastogenesis has been well-characterized in mouse models, many questions remain regarding the regulation of osteoclast formation in human diseases. We examined the regulation of human precursors induced to differentiate and fuse into multinucleated osteoclasts by receptor activator of nuclear factor kappa-B ligand (RANKL. High-content single cell microscopy enabled the time-resolved quantification of both the population of monocytic precursors and the emerging osteoclasts. We observed that prior to induction of osteoclast fusion, RANKL stimulated precursor proliferation, acting in part through an autocrine mediator. Cytokines secreted during osteoclastogenesis were resolved using multiplexed quantification combined with a Partial Least Squares Regression model to identify the relative importance of specific cytokines for the osteoclastogenesis outcome. Interleukin 8 (IL-8 was identified as one of RANKL-induced cytokines and validated for its role in osteoclast formation using inhibitors of the IL-8 cognate receptors CXCR1 and CXCR2 or an IL-8 blocking antibody. These insights demonstrate that autocrine signaling induced by RANKL represents a key regulatory component of human osteoclastogenesis.

  12. How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound Repair

    Directory of Open Access Journals (Sweden)

    Peter Gál

    2017-10-01

    Full Text Available It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive scar formation. In the present review paper, we define key signaling molecules (growth factors, cytokines, chemokines, and galectins involved in the formation of the tumor microenvironment that decrease overall survival and increase drug resistance in cancer suffering patients. Additional attention will also be given to show whether targeted modulation of these regulators promote tissue regeneration and wound management. Whole-genome transcriptome profiling, in vitro and animal experiments revealed that interleukin 6, interleukin 8, chemokine (C-X-C motif ligand 1, galectin-1, and selected proteins of the extracellular matrix (e.g., fibronectin do have similar regulation during wound healing and tumor growth. Published data demonstrate remarkable similarities between the tumor and wound microenvironments. Therefore, tailor made manipulation of cancer stroma can have important therapeutic consequences. Moreover, better understanding of cancer cell-stroma interaction can help to improve wound healing by supporting granulation tissue formation and process of reepithelization of extensive and chronic wounds as well as prevention of hypertrophic scars and formation of keloids.

  13. The IL-8 protease SpyCEP/ScpC of group A Streptococcus promotes resistance to neutrophil killing.

    Science.gov (United States)

    Zinkernagel, Annelies S; Timmer, Anjuli M; Pence, Morgan A; Locke, Jeffrey B; Buchanan, John T; Turner, Claire E; Mishalian, Inbal; Sriskandan, Shiranee; Hanski, Emanuel; Nizet, Victor

    2008-08-14

    Interleukin-8 (IL-8) promotes neutrophil-mediated host defense through its chemoattractant and immunostimulatory activities. The Group A Streptococcus (GAS) protease SpyCEP (also called ScpC) cleaves IL-8, and SpyCEP expression is strongly upregulated in vivo in the M1T1 GAS strains associated with life-threatening systemic disease including necrotizing fasciitis. Coupling allelic replacement with heterologous gene expression, we show that SpyCEP is necessary and sufficient for IL-8 degradation. SpyCEP decreased IL-8-dependent neutrophil endothelial transmigration and bacterial killing, the latter by reducing neutrophil extracellular trap formation. The knockout mutant lacking SpyCEP was attenuated for virulence in murine infection models, and SpyCEP expression conferred protection to coinfecting bacteria. We also show that the zoonotic pathogen Streptococcus iniae possesses a functional homolog of SpyCEP (CepI) that cleaves IL-8, promotes neutrophil resistance, and contributes to virulence. By inactivating the multifunctional host defense peptide IL-8, the SpyCEP protease impairs neutrophil clearance mechanisms, contributing to the pathogenesis of invasive streptococcal infection.

  14. The CXC Chemokine-degrading Protease SpyCep of Streptococcus pyogenes Promotes Its Uptake into Endothelial Cells*

    Science.gov (United States)

    Kaur, Simran Jeet; Nerlich, Andreas; Bergmann, Simone; Rohde, Manfred; Fulde, Marcus; Zähner, Dorothea; Hanski, Emanuel; Zinkernagel, Annelies; Nizet, Victor; Chhatwal, Gursharan S.; Talay, Susanne R.

    2010-01-01

    Streptococcus pyogenes expresses the LPXTG motif-containing cell envelope serine protease SpyCep (also called ScpC, PrtS) that degrades and inactivates the major chemoattractant interleukin 8 (IL-8), thereby impairing host neutrophil recruitment. In this study, we identified a novel function of SpyCep: the ability to mediate uptake into primary human endothelial cells. SpyCep triggered its uptake into endothelial cells but not into human epithelial cells originating from pharynx or lung, indicating an endothelial cell-specific uptake mechanism. SpyCep mediated cellular invasion by an endosomal/lysosomal pathway distinct from the caveolae-mediated invasion pathway of S. pyogenes. Recombinant expression and purification of proteolytically active SpyCep and a series of subfragments allowed functional dissection of the domains responsible for endothelial cell invasion and IL-8 degradation. The N-terminal PR domain was sufficient to mediate endothelial cell invasion, whereas for IL-8-degrading activity, the protease domain and the flanking A domain were required. A polyclonal rabbit serum raised against the recombinant protease efficiently blocked the invasion-mediating activity of SpyCep but not its proteolytic function, further indicating that SpyCep-mediated internalization is independent from its enzymatic activity. SpyCep may thus specifically mediate its own uptake as secreted protein into human endothelial cells. PMID:20562101

  15. The ScpC Protease of Streptococcus pyogenes Affects the Outcome of Sepsis in a Murine Model ▿

    Science.gov (United States)

    Sjölinder, Hong; Lövkvist, Lena; Plant, Laura; Eriksson, Jens; Aro, Helena; Jones, Allison; Jonsson, Ann-Beth

    2008-01-01

    The ScpC protease of Streptococcus pyogenes degrades interleukin-8 (IL-8), a chemokine that mediates neutrophil transmigration and activation. The ability to degrade IL-8 differs dramatically among clinical isolates of S. pyogenes. Bacteria expressing ScpC overcome immune clearance by preventing the recruitment of neutrophils in soft tissue infection of mice. To study the role of ScpC in streptococcal sepsis, we generated an ScpC mutant that did not degrade IL-8 and thus failed to prevent the recruitment of immune cells as well as to cause disease after soft tissue infection. In a murine model of sepsis, challenge with the ScpC mutant resulted in more severe systemic disease with higher bacteremia levels and mortality than did challenge with the wild-type strain. As expected, the blood level of KC, the murine IL-8 homologue, increased in mice infected with the ScpC mutant. However, the elevated KC levels did not influence neutrophil numbers in blood, as it did in soft tissue, indicating that additional factors contributed to neutrophil transmigration in blood. In addition, the absence of ScpC increased tumor necrosis factor, IL-6, and C5a levels in blood, which contributed to disease severity. Thus, the ScpC mutant triggers high neutrophil infiltration but not lethal outcome after soft tissue infection, whereas intravenous infection leads to highly aggressive systemic disease. PMID:18573900

  16. The CXC chemokine-degrading protease SpyCep of Streptococcus pyogenes promotes its uptake into endothelial cells.

    Science.gov (United States)

    Kaur, Simran Jeet; Nerlich, Andreas; Bergmann, Simone; Rohde, Manfred; Fulde, Marcus; Zähner, Dorothea; Hanski, Emanuel; Zinkernagel, Annelies; Nizet, Victor; Chhatwal, Gursharan S; Talay, Susanne R

    2010-09-03

    Streptococcus pyogenes expresses the LPXTG motif-containing cell envelope serine protease SpyCep (also called ScpC, PrtS) that degrades and inactivates the major chemoattractant interleukin 8 (IL-8), thereby impairing host neutrophil recruitment. In this study, we identified a novel function of SpyCep: the ability to mediate uptake into primary human endothelial cells. SpyCep triggered its uptake into endothelial cells but not into human epithelial cells originating from pharynx or lung, indicating an endothelial cell-specific uptake mechanism. SpyCep mediated cellular invasion by an endosomal/lysosomal pathway distinct from the caveolae-mediated invasion pathway of S. pyogenes. Recombinant expression and purification of proteolytically active SpyCep and a series of subfragments allowed functional dissection of the domains responsible for endothelial cell invasion and IL-8 degradation. The N-terminal PR domain was sufficient to mediate endothelial cell invasion, whereas for IL-8-degrading activity, the protease domain and the flanking A domain were required. A polyclonal rabbit serum raised against the recombinant protease efficiently blocked the invasion-mediating activity of SpyCep but not its proteolytic function, further indicating that SpyCep-mediated internalization is independent from its enzymatic activity. SpyCep may thus specifically mediate its own uptake as secreted protein into human endothelial cells.

  17. The ScpC protease of Streptococcus pyogenes affects the outcome of sepsis in a murine model.

    Science.gov (United States)

    Sjölinder, Hong; Lövkvist, Lena; Plant, Laura; Eriksson, Jens; Aro, Helena; Jones, Allison; Jonsson, Ann-Beth

    2008-09-01

    The ScpC protease of Streptococcus pyogenes degrades interleukin-8 (IL-8), a chemokine that mediates neutrophil transmigration and activation. The ability to degrade IL-8 differs dramatically among clinical isolates of S. pyogenes. Bacteria expressing ScpC overcome immune clearance by preventing the recruitment of neutrophils in soft tissue infection of mice. To study the role of ScpC in streptococcal sepsis, we generated an ScpC mutant that did not degrade IL-8 and thus failed to prevent the recruitment of immune cells as well as to cause disease after soft tissue infection. In a murine model of sepsis, challenge with the ScpC mutant resulted in more severe systemic disease with higher bacteremia levels and mortality than did challenge with the wild-type strain. As expected, the blood level of KC, the murine IL-8 homologue, increased in mice infected with the ScpC mutant. However, the elevated KC levels did not influence neutrophil numbers in blood, as it did in soft tissue, indicating that additional factors contributed to neutrophil transmigration in blood. In addition, the absence of ScpC increased tumor necrosis factor, IL-6, and C5a levels in blood, which contributed to disease severity. Thus, the ScpC mutant triggers high neutrophil infiltration but not lethal outcome after soft tissue infection, whereas intravenous infection leads to highly aggressive systemic disease.

  18. Effects of arginine on multimodal anion exchange chromatography.

    Science.gov (United States)

    Hirano, Atsushi; Arakawa, Tsutomu; Kameda, Tomoshi

    2015-12-01

    The effects of arginine on binding and elution properties of a multimodal anion exchanger, Capto adhere, were examined using bovine serum albumin (BSA) and a monoclonal antibody against interleukin-8 (mAb-IL8). Negatively charged BSA was bound to the positively charged Capto adhere and was readily eluted from the column with a stepwise or gradient elution using 1M NaCl at pH 7.0. For heat-treated BSA, small oligomers and remaining monomers were also eluted using a NaCl gradient, whereas larger oligomers required arginine for effective elution. The positively charged mAb-IL8 was bound to Capto adhere at pH 7.0. Arginine was also more effective for elution of the bound mAb-IL8 than was NaCl. The results imply that arginine interacts with the positively charged Capto adhere. The mechanism underlying the interactions of arginine with Capto adhere was examined by calculating the binding free energy between an arginine molecule and a Capto adhere ligand in water through molecular dynamics simulations. The overall affinity of arginine for Capto adhere is attributed to the hydrophobic and π-π interactions between an arginine side chain and the aromatic moiety of the ligand as well as hydrogen bonding between arginine and the ligand hydroxyl group, which may account for the characteristics of protein elution using arginine. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Circulating microparticles carry oxidation-specific epitopes and are recognized by natural IgM antibodies.

    Science.gov (United States)

    Tsiantoulas, Dimitrios; Perkmann, Thomas; Afonyushkin, Taras; Mangold, Andreas; Prohaska, Thomas A; Papac-Milicevic, Nikolina; Millischer, Vincent; Bartel, Caroline; Hörkkö, Sohvi; Boulanger, Chantal M; Tsimikas, Sotirios; Fischer, Michael B; Witztum, Joseph L; Lang, Irene M; Binder, Christoph J

    2015-02-01

    Oxidation-specific epitopes (OSEs) present on apoptotic cells and oxidized low density lipoprotein (OxLDL) represent danger-associated molecular patterns that are recognized by different arcs of innate immunity, including natural IgM antibodies. Here, we investigated whether circulating microparticles (MPs), which are small membrane vesicles released by apoptotic or activated cells, are physiological carriers of OSEs. OSEs on circulating MPs isolated from healthy donors and patients with ST-segment elevation myocardial infarction (STE-MI) were characterized by flow cytometry using a panel of OSE-specific monoclonal antibodies. We found that a subset of MPs carry OSEs on their surface, predominantly malondialdehyde (MDA) epitopes. Consistent with this, a majority of IgM antibodies bound on the surface of circulating MPs were found to have specificity for MDA-modified LDL. Moreover, we show that MPs can stimulate THP-1 (human acute monocytic leukemia cell line) and human primary monocytes to produce interleukin 8, which can be inhibited by a monoclonal IgM with specificity for MDA epitopes. Finally, we show that MDA(+) MPs are elevated at the culprit lesion site of patients with STE-MI. Our results identify a subset of OSE(+) MPs that are bound by OxLDL-specific IgM. These findings demonstrate a novel mechanism by which anti-OxLDL IgM antibodies could mediate protective functions in CVD. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  20. Severe Re-expansion Pulmonary Edema Induced by One-Lung Ventilation.

    Science.gov (United States)

    Sugiyama, Yuki; Shimizu, Fumiko; Shimizu, Sari; Urasawa, Masatoshi; Tanaka, Satoshi; Kawamata, Mikito

    2015-08-01

    We present 2 cases of severe re-expansion pulmonary edema (RPE) after one-lung ventilation (OLV) for thoracic surgery. A 32-y-old woman with multiple lung metastases developed severe RPE after OLV during lung resection surgery. A 37-y-old man with infective endocarditis also developed severe RPE after OLV for mitral valve plasty with minimally invasive cardiac surgery. In both cases, results of a preoperative pulmonary function test and oxygenation were almost normal, and pleural effusion or pulmonary congestion was not detected in preoperative computed tomography; however, there was a possibility that subclinical lung injury existed before surgery. The levels of interleukin-8 and monocyte chemotactic protein-1, which are thought to play important roles in the development of lung injury, in bronchial secretions were extremely high after the onset of RPE. These results suggest that the pathogenesis of RPE shares, at least in part, a common pathophysiology of acute lung injury. Copyright © 2015 by Daedalus Enterprises.

  1. Probiotic screening and safety evaluation of Lactobacillus strains from plants, artisanal goat cheese, human stools, and breast milk.

    Science.gov (United States)

    Gotteland, Martin; Cires, Maria Jose; Carvallo, Claudia; Vega, Natalia; Ramirez, Maria Antonieta; Morales, Pamela; Rivas, Patricia; Astudillo, Fernanda; Navarrete, Paola; Dubos, Céline; Figueroa, Alvaro; Troncoso, Miriam; Ulloa, Carolina; Mizgier, Maria Luisa; Carrasco-Pozo, Catalina; Speisky, Hernan; Brunser, Oscar; Figueroa, Guillermo

    2014-04-01

    The aim of this study was to select autochthonous strains of Lactobacillus from stools of healthy infants and adults, human milk, artisanal goat cheese, and fruits and vegetables according to their probiotic properties and safety. From 421 strains of Lactobacillus isolated, 102 (24.2%) were shown to be tolerant to gastric pH and bile salts; they were used to determine their anti-Helicobacter pylori (agar diffusion assay), antioxidant (oxygen radical absorption capacity), and anti-inflammatory (inhibition of interleukin-8 release by tumor necrosis factor-α-stimulated HT-29 cells) activities as well as their ability to adhere to intestinal (Caco-2) and gastric (AGS) epithelial cells. Results obtained were compared with three commercial probiotic Lactobacillus rhamnosus GG, L. plantarum 299v, and L. johnsonii NCC533. The five strains most efficient according to these activities were subsequently identified by sequencing their 16S rRNA gene, their susceptibility to antibiotics was determined, and their safety evaluated in mice. One strain of L. plantarum was discarded due to the higher prevalence of liver bacterial translocation observed in the animals fed this strain. In conclusion, four autochthonous strains of L. rhamnosus were finally selected with probiotic properties and safety allowing their eventual use in human studies. These results contribute to increase the diversity of probiotic strains available for the development of nutraceuticals and functional foods.

  2. Comparative effectiveness of methylprednisolone and zero-balance ultrafiltration on inflammatory response after pediatric cardiopulmonary bypass.

    Science.gov (United States)

    Liu, Jinping; Ji, Bingyang; Long, Cun; Li, Chunhua; Feng, Zhengyi

    2007-07-01

    Studies have demonstrated that systemic inflammatory response syndrome (SIRS) remains one of the major causes of cardiopulmonary bypass (CPB)-associated organ injury during pediatric cardiac surgery. The purpose of this investigation was to compare the effectiveness of methylprednisolone (MP) and zero-balance ultrafiltration (ZBUF) on SIRS during pediatric CPB. Thirty infants undergoing open-heart surgeries were randomized to receive either MP in the priming solution (group M, n = 15) or ZBUF during CPB (group Z, n = 15). All the patients survived. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured before CPB (T1), 5 min after the start of CPB (T2), at the termination of CPB (T3), the fourth hour (T4), and the eighth hour (T5) postoperatively. The results showed that the plasma concentrations of TNF-alpha in the Z group were significantly less than those in the M group at T4 and T5 (P alpha, IL-6, and IL-8 than administration of MP after pediatric CPB.

  3. Effects of prostaglandin E1 on reperfusion injury patients: A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhu, Houyong; Xu, Xiaoqun; Ding, Yu; Zhou, Liang; Huang, Jinyu

    2017-04-01

    Prostaglandin E1 (PGE1) is widely used as a pretreatment for myocardial reperfusion injury in animal experiments. However, the cardioprotective effects of PGE1 in patients have not been established. We performed a meta-analysis to investigate whether PGE1 is cardioprotective, based on the reduction of correlative reperfusion injury events (CRIE), major adverse cardiac events (MACE), and biomarker release in patients with ischemia reperfusion injury. The Medline, EMBASE, and Cochrane databases were searched for randomized clinical trials confirming the effects of PGE1. Two investigators independently selected suitable trials, assessed trial quality, and extracted data. Six studies in patients undergoing percutaneous coronary intervention (4 studies) and cardiac surgery (2 studies), comprising a total of 445 patients, were included in this review. The results showed that PGE1 reduced the incidence of CRIE (relative ratio 0.4 [95% confidence interval 0.43, 0.95]), the incidence of MACE (0.35 [0.17, 0.70]), and the level of troponin T (standardized mean difference 20.28 [20.47, 20.09]), creatine kinase-MB (-1.74 [-3.21, - 0.27]), interleukin-6 (-1.37 [-2.69, - 0.04]), and interleukin-8 (-2.05 [-2.75, - 1.34]). PGE1 may have beneficial effects on myocardial reperfusion injury in the clinic.

  4. Immunometabolic parameters in overweight dogs during weight loss with or without an exercise program.

    Science.gov (United States)

    Vitger, A D; Stallknecht, B M; Miles, J E; Hansen, S L; Vegge, A; Bjørnvad, C R

    2017-04-01

    The influence of physical activity on metabolic health in overweight dogs is unknown. This study was conducted to evaluate biomarkers of immunometabolic health in relation to changes in physical activity and adiposity. Client-owned overweight dogs participated in a 12-wk intervention based on caloric restriction combined with a training program (fitness and diet [FD] group, n = 8), or caloric restriction alone (diet-only [DO] group, n = 8). Physical activity was monitored by accelerometry. All dogs were fed the same diet and achieved similar weight loss. Fasting blood samples were collected before and after 6- and 12-wk intervention. Insulin resistance was evaluated from plasma insulin and C-peptide as well as homeostasis model assessment. Inflammation and dyslipidemia were evaluated from circulating leptin, adiponectin, C-reactive protein (CRP), monocyte chemoattractant factor-1 (MCP-1), interleukin-8 (IL-8), and cholesterol. Accelerometer counts in both groups were high compared with previous reports of physical activity in overweight dogs. No difference in blood parameters was evident between groups, evaluated by linear mixed-effects model (P > 0.05). Within the groups, the following changes were significant by t-test (P benefits. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Accuracy of several maternal seric markers for predicting histological chorioamnionitis after preterm premature rupture of membranes: a prospective and multicentric study.

    Science.gov (United States)

    Caloone, Jonathan; Rabilloud, Muriel; Boutitie, Florent; Traverse-Glehen, Alexandra; Allias-Montmayeur, Fabienne; Denis, Laure; Boisson-Gaudin, Catherine; Hot, Isabelle Jaisson; Guerre, Pascale; Cortet, Marion; Huissoud, Cyril

    2016-10-01

    To assess and compare several maternal seric markers for the prediction of histological chorioamnionitis (HCA) after preterm premature rupture of membranes (PPROM). Study design A prospective and multicentric observational study was undertaken, including six French tertiary referral centres. Pregnant women over 18 years, with PPROM between 22+0 and 36+6 WG were enrolled. A blood sample was obtained before delivery and analysed for C-Reactive Protein (CRP), InterCellular Adhesion Molecule-1 (ICAM-1), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Matrix-Metalloproteinase 8 and 9 (MMP-8, MMP-9), Triggering receptor on myeloid cells (TREM-1), and Human Neutrophile Peptides (HNP). HCA was determined by histological examination distinguishing maternal from fetal inflammatory response. Placental analyses and biological assays were performed in duplicate. Comparison of maternal seric markers levels in women with or vs. without HCA was performed, using a non-parametric Receiver Operating Characteristic. 295 women were kept for analysis. The prevalence of HCA was 42.7% (126/295). The concentrations of MMP-8, MMP-9, HNP and CRP were higher in HCA vs. the non-HCA group (P0.05). The ROC curve with the largest AUC was for CRP (AUC; 0.70; 95% CI; 0.64-0.77) and it was significantly higher than those for MMP-8, MMP-9, or HNP (P<0.03). CRP was the best maternal marker for predicting HCA in women with PPROM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Necrotic foci, elevated chemokines and infiltrating neutrophils in the liver of glycogen storage disease type Ia

    Science.gov (United States)

    Kim, So Youn; Weinstein, David A.; Starost, Matthew F.; Mansfield, Brian C.; Chou, Janice Y.

    2009-01-01

    Background/Aims Glycogen storage disease type Ia (GSD-Ia) patients manifest the long-term complication of hepatocellular adenoma (HCA) of unknown etiology. We showed previously that GSD-Ia mice exhibit neutrophilia and elevated serum cytokine levels. This study was conducted to evaluate whether human GSD-Ia patients exhibit analogous increases and whether in GSD-Ia mice a correlation exists between immune abnormalities and, biochemical and histological alterations in the liver. Methods Differential leukocyte counts and cytokine levels were investigated in GSD-Ia patients. Hepatic chemokine production, neutrophil infiltration, and histological abnormalities were investigated in GSD-Ia mice. Results We show that GSD-Ia patients exhibit increased peripheral neutrophil counts and serum interleukin-8 (IL-8). Compared to normal subjects, HCA-bearing GSD-Ia patients have a 2.8-fold higher serum IL8 concentration, while GSD-Ia patients without HCA have a 1.4-fold higher concentration. Hepatic injury in GSD-Ia mice is evidenced by necrotic foci, markedly elevated infiltrating neutrophils, and increased hepatic production of chemokines. Conclusion Peripheral neutrophilia and elevated serum chemokines are characteristic of GSD-Ia with HCA-bearing GSD-Ia patients having the highest serum IL-8. In GSD-Ia mice these elevations correlate with elevated hepatic chemokine levels, neutrophil infiltration, and necrosis. Taken together, peripheral neutrophilia and increased serum chemokines may indicate hepatic injuries in GSD-Ia PMID:18191274

  7. Quasi-total-body exposure to an oxygen-ozone mixture in a sauna cabin.

    Science.gov (United States)

    Bocci, V; Borrelli, E; Valacchi, G; Luzzi, E

    1999-01-01

    We have investigated the effects of quasi-total-body exposure of healthy volunteers to either an oxygen-ozone mixture (O(2)-O(3)) or to oxygen (O(2)) alone during a short period in a sauna cabin. The subjects underwent both an experimental and a control examination, separated by a 3.5-month interval. Body mass, blood pressure, body temperature changes, electrocardiograms, venous blood gas and haemocytometric analyses, total antioxidant status and plasma levels of protein thiol groups, thiobarbituric acid reactive substances (TBARS), plasma cytokine, hepatic enzymes and creatine were determined before, immediately after the 20-min period in the cabin and then 0.5, 1.0 and 24 h afterwards. We observed statistically significant variations of body temperature, venous partial pressure of O(2) values, TBARS and plasma levels of interleukin 8, particularly after O(2)-O(3) exposure. The increase in TBARS plasma levels concomitant with protein oxidation has been tentatively interpreted as being attributable to the transcutaneous passage of some reactive O(2) species, which should be considered if this approach is to be used as a biological response modifier. However, in the present study no adverse effects were noted after one session.

  8. Alteration in peripheral blood concentration of certain pro-inflammatory cytokines in cows developing retention of fetal membranes.

    Science.gov (United States)

    Boro, Prasanta; Kumaresan, A; Pathak, Rupal; Patbandha, T K; Kumari, Susavi; Yadav, Asha; Manimaran, A; Baithalu, R K; Attupuram, Nitin M; Mohanty, T K

    2015-06-01

    Retention of fetal membranes (RFM) adversely affects the production and reproduction potential of the affected cows leading to huge economic loss. Physiological separation of fetal membranes is reported to be an inflammatory process. The present study compared the concentrations of certain pro inflammatory cytokines [Interleukin 1β (IL-1), Interleukin 6 (IL-6), Interleukin 8 (IL-8) and Tumor necrosis factor α (TNF-α) between the cows that developed RFM (n=10) and the cows that expelled fetal membranes normally (n=10) to find out if they could serve as a predictive tool for RFM. Blood samples were collected from the cows from 30 days before expected parturition through day -21, day -14, day -7, day -5, day -3, day -1, on the day of parturition (day 0), day 1 postpartum and the pro-inflammatory cytokines were estimated in blood plasma by ELISA method. The IL-1β concentration was significantly lower (Pmembranes normally from 3 days before calving till the day of calving. The plasma concentrations of IL-6 and IL-8 were also lower (Pmembranes normally. It may be inferred that the concentrations of IL-1, IL-6, IL-8 and TNF-α around parturition were altered in cows developing RFM compared to those expelled fetal membranes normally. Copyright © 2015. Published by Elsevier B.V.

  9. Simultaneous ultrasound-assisted water extraction and β-cyclodextrin encapsulation of polyphenols from Mangifera indica stem bark in counteracting TNFα-induced endothelial dysfunction.

    Science.gov (United States)

    Mura, Marzia; Palmieri, Daniela; Garella, Davide; Di Stilo, Antonella; Perego, Patrizia; Cravotto, Giancarlo; Palombo, Domenico

    2015-01-01

    This study proposes an alternative technique to prevent heat degradation induced by classic procedures of bioactive compound extraction, comparing classical maceration/decoction in hot water of polyphenols from Mango (Mangifera indica L.) (MI) with ultrasound-assisted extraction (UAE) in a water solution of β-cyclodextrin (β-CD) at room temperature and testing their biological activity on TNFα-induced endothelial dysfunction. Both extracts counteracted TNFα effects on EAhy926 cells, down-modulating interleukin-6, interleukin-8, cyclooxygenase-2 and intracellular adhesion molecule-1, while increasing endothelial nitric oxide synthase levels. β-CD extract showed higher efficacy in improving endothelial function. These effects were abolished after pre-treatment with the oestrogen receptor inhibitor ICI1182,780. Moreover, the β-CD extract induced Akt activation and completely abolished the TNFα-induced p38MAPK phosphorylation. UAE and β-CD encapsulation provide an efficient extraction protocol that increases polyphenol bioavailability. Polyphenols from MI play a protective role on endothelial cells and may be further considered as oestrogen-like molecules with vascular protective properties.

  10. A-Type Cranberry Proanthocyanidins Inhibit the RANKL-Dependent Differentiation and Function of Human Osteoclasts

    Directory of Open Access Journals (Sweden)

    Amy B. Howell

    2011-03-01

    Full Text Available This study investigated the effect of A-type cranberry proanthocyanidins (AC-PACs on osteoclast formation and bone resorption activity. The differentiation of human pre-osteoclastic cells was assessed by tartrate-resistant acid phosphatase (TRAP staining, while the secretion of interleukin-8 (IL-8 and matrix metalloproteinases (MMPs was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen helical peptides. AC-PACs up to 100 µg/mL were atoxic for osteoclastic cells. TRAP staining evidenced a dose-dependent inhibition of osteoclastogenesis. More specifically, AC-PACs at 50 µg/mL caused a 95% inhibition of RANKL-dependent osteoclast differentiation. This concentration of AC-PACs also significantly increased the secretion of IL-8 (6-fold and inhibited the secretion of both MMP-2 and MMP-9. Lastly, AC-PACs (10, 25, 50 and 100 µg/ml affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides. This study suggests that AC-PACs can interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption. These compounds may be considered as therapeutic agents for the prevention and treatment of periodontitis.

  11. The role of prostaglandins E1 and E2, dinoprostone, and misoprostol in cervical ripening and the induction of labor: a mechanistic approach.

    Science.gov (United States)

    Bakker, Ronan; Pierce, Stephanie; Myers, Dean

    2017-08-01

    Prostaglandins play a critical role in cervical ripening by increasing inflammatory mediators in the cervix and inducing cervical remodeling. Prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2) exert different effects on these processes and on myometrial contractility. These mechanistic differences may affect outcomes in women treated with dinoprostone, a formulation identical to endogenous PGE2, compared with misoprostol, a PGE1 analog. The objective of this review is to evaluate existing evidence regarding mechanistic differences between PGE1 and PGE2, and consider the clinical implications of these differences in patients requiring cervical ripening for labor induction. We conducted a critical narrative review of peer-reviewed articles identified using PubMed and other online databases. While both dinoprostone and misoprostol are effective in cervical ripening and labor induction, they differ in their clinical and pharmacological profiles. PGE2 has been shown to stimulate interleukin-8, an inflammatory cytokine that promotes the influx of neutrophils and induces remodeling of the cervical extracellular matrix, and to induce functional progesterone withdrawal. Misoprostol has been shown to elicit a dose-dependent effect on myometrial contractility, which may affect rates of uterine tachysystole in clinical practice. Differences in the mechanism of action between misoprostol and PGE2 may contribute to their variable effects in the cervix and myometrium, and should be considered to optimize outcomes.

  12. In Vitro Evaluation of a Biomedical-Grade Bilayer Chitosan Porous Skin Regenerating Template as a Potential Dermal Scaffold in Skin Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Chin Keong Lim

    2011-01-01

    Full Text Available Chitosan is a copolymer of N-acetylglucosamine and glucosamine. A bilayer chitosan porous skin regenerating template (CPSRT has been developed for skin tissue engineering. The pore size of the CPSRT was assessed using a scanning electron microscopy (SEM. The in vitro cytocompatibility of the CPSRT was tested on primary human epidermal keratinocyte (pHEK cultures by measuring lactate dehydrogenase (LDH levels and skin irritation by western blot analysis of the interleukin-8 (IL-8 and tumor necrosis factor-α (TNF-α secretions. The ability of the CPSRT to support cell ingrowth was evaluated by seeding primary human dermal fibroblasts (pHDFs on the scaffold, staining the cells with live/dead stain, and imaging the construct by confocal microscopy (CLSM. The CPSRT with pore sizes ranging from 50 to 150 μm was cytocompatible because it did not provoke the additional production of IL-8 and TNF-α by pHEK cultures. Cultured pHDFs were able to penetrate the CPSRT and had increased in number on day 14. In conclusion, the CPSRT serves as an ideal template for skin tissue engineering.

  13. Decidualized Human Endometrial Stromal Cells Mediate Hemostasis, Angiogenesis, and Abnormal Uterine Bleeding

    Science.gov (United States)

    Lockwood, Charles J.; Krikun, Graciela; Hickey, Martha; Huang, S. Joseph; Schatz, Frederick

    2011-01-01

    Factor VII binds trans-membrane tissue factor to initiate hemostasis by forming thrombin. Tissue factor expression is enhanced in decidualized human endometrial stromal cells during the luteal phase. Long-term progestin only contraceptives elicit: 1) abnormal uterine bleeding from fragile vessels at focal bleeding sites, 2) paradoxically high tissue factor expression at bleeding sites; 3) reduced endometrial blood flow promoting local hypoxia and enhancing reactive oxygen species levels; and 4) aberrant angiogenesis reflecting increased stromal cell-expressed vascular endothelial growth factor, decreased Angiopoietin-1 and increased endothelial cell-expressed Angiopoietin-2. Aberrantly high local vascular permeability enhances circulating factor VII to decidualized stromal cell-expressed tissue factor to generate excess thrombin. Hypoxia-thrombin interactions augment expression of vascular endothelial growth factor and interleukin-8 by stromal cells. Thrombin, vascular endothelial growth factor and interlerukin-8 synergis-tically augment angiogenesis in a milieu of reactive oxygen species-induced endothelial cell activation. The resulting enhanced vessel fragility promotes abnormal uterine bleeding. PMID:19208784

  14. Overfilling of calcium hydroxide-based paste Calcipex II produced a foreign body granuloma without acute inflammatory reaction.

    Science.gov (United States)

    Kim, Jin Woo; Cho, Kyung Mo; Park, Se Hee; Song, Seung Gon; Park, Mi Sun; Jung, Hye Rim; Song, Ji Yong; Kim, Yeon Sook; Lee, Suk Keun

    2009-03-01

    A patient, a 62-year-old man, received endodontic treatment of the lower left canine complicated by apical overfilling of Calcipex II. At the second day after the root canal filling, the 14th day after placement of Calcipex II intracanal medication, he complained of a gingival swelling in the treated area. The incisional biopsy of the gingival swelling revealed a foreign body granuloma infiltrated with macrophages engulfing the fine Calcipex II granules but with polymorphonuclear leukocytes (PMNs). However, the gingival swelling was healed uneventfully, and the tooth was free of symptoms at 4 months' follow-up. This study first reports the Calcipex II-induced reaction in human periodontium. In the immunohistochemistry using antisera of lysozyme, CD31, CD68, interleukin-8 (IL-8), and poly(ADP-ribose) polymerase 1 (PARP-1), the granule-laden cells are positive for lysozyme, CD31, CD68, and PARP-1, but negative for IL-8. Thus, it is presumed that the granule-laden cells belong to the macrophages/monocytes rather than the PMNs, and that they gradually undergo the apoptotic processes. These data suggest that the canal dressing material, Calcipex II, is able to be widely dispersed into the periodontal tissues, primarily engulfed by macrophages, and resulted in the foreign body granuloma in the absence of acute inflammatory reaction.

  15. The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines.

    Science.gov (United States)

    Li, B Q; Fu, T; Gong, W H; Dunlop, N; Kung, H; Yan, Y; Kang, J; Wang, J M

    2000-09-01

    Baicalin (BA) is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to possess anti-inflammatory and anti-viral activities. In order to elucidate the mechanism(s) of action of BA, we tested whether BA could interfere with chemokines or chemokine receptors, which are critical mediators of inflammation and infection. We observed that BA inhibited the binding of a number of chemokines to human leukocytes or cells transfected to express specific chemokine receptors. This was associated with a reduced capacity of the chemokines to induce cell migration. Co-injection of BA with CXC chemokine interleukin-8 (IL-8) into rat skin significantly inhibited IL-8 elicited neutrophil infiltration. BA did not directly compete with chemokines for binding to receptors, but rather acted through its selective binding to chemokine ligands. This conclusion was supported by the fact that BA cross-linked to oxime resin bound chemokines of the CXC (stromal cell-derived factor (SDF)-1alpha, IL-8), CC (macrophage inflammatory protein (MIP)-1beta, monocyte chemotactic protein (MCP)-2), and C (lymphotactin (Ltn)) subfamilies. BA did not interact with CX3C chemokine fractalkine/neurotactin or other cytokines, such as TNF-alpha and IFN-gamma, indicating that its action is selective. These results suggest that one possible anti-inflammatory mechanism of BA is to bind a variety of chemokines and limit their biological function.

  16. Bone marrow-derived mesenchymal stem cell-secreted IL-8 promotes the angiogenesis and growth of colorectal cancer.

    Science.gov (United States)

    Wang, Jiancheng; Wang, Yingnan; Wang, Shaochuan; Cai, Jianye; Shi, Jianqiang; Sui, Xin; Cao, Yong; Huang, Weijun; Chen, Xiaoyong; Cai, Zijie; Li, Hongyu; Bardeesi, Adham Sameer A; Zhang, Bin; Liu, Muyun; Song, Wu; Wang, Maosheng; Xiang, Andy Peng

    2015-12-15

    Mesenchymal stem cells (MSCs) have recently been shown to home to tumors and contribute to the formation of the tumor-associated stroma. In addition, MSCs can secrete paracrine factors to facilitate tumor progression. However, the involvement of MSC-derived cytokines in colorectal cancer (CRC) angiogenesis and growth has not been clearly addressed. In this study, we report that interleukin-8 (IL-8) was the most highly upregulated pro-angiogenic factor in MSCs co-cultured with CRC cells and was expressed at substantially higher levels in MSCs than CRC cells. To evaluate the effect of MSC-derived IL-8 on CRC angiogenesis and growth, we used MSCs that expressed small hairpin (interfering) RNAs (shRNA) targeting IL-8 (shIL-8-MSCs). We found that MSC-secreted IL-8 promoted human umbilical vein endothelial cell (HUVEC) proliferation and migration, tube-formation ability and CRC cell proliferation. Additionally, in vivo studies showed that MSCs promoted tumor angiogenesis partially through IL-8. Taken together, these findings suggest that IL-8 secreted by MSCs promotes CRC angiogenesis and growth and can therefore serve as a potential novel therapeutic target.

  17. Assessment of Blood Flow in Hepatocellular Carcinoma: Correlations of Computed Tomography Perfusion Imaging and Circulating Angiogenic Factors

    Directory of Open Access Journals (Sweden)

    Chen-Pin Chou

    2013-08-01

    Full Text Available Hepatocellular carcinoma (HCC is a highly vascular tumor through the process of angiogenesis. To evaluate more non-invasive techniques for assessment of blood flow (BF in HCC, this study examined the relationships between BF of HCC measured by computer tomography (CT perfusion imaging and four circulating angiogenic factors in HCC patients. Interleukin 6 (IL-6, interleukin 8 (IL-8, vascular endothelial growth factor (VEGF, and platelet derived growth factor (PDGF in plasma were measured using Bio-Plex multiplex immunoassay in 21 HCC patients and eight healthy controls. Circulating IL-6, IL-8 and VEGF showed higher concentrations in HCC patients than in controls (p < 0.05, and predicted HCC occurrence better than chance (p < 0.01. Twenty-one patients with HCC received 21-phase liver imaging using a 64-slice CT. Total BF, arterial BF, portal BF, arterial fraction (arterial BF/total BF of the HCC and surrounding liver parenchyma, and HCC-parenchyma ratio were measured using a dual-vessel model. After analyzing the correlations between BF in HCC and four circulating angiogenic factors, we found that the HCC-parenchyma ratio of arterial BF showed a significantly positive correlation with the level of circulating IL-8 (p < 0.05. This circulating biomarker, IL-8, provides a non-invasive tool for assessment of BF in HCC.

  18. IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells.

    Science.gov (United States)

    Schinke, Carolina; Giricz, Orsolya; Li, Weijuan; Shastri, Aditi; Gordon, Shanisha; Barreyro, Laura; Barreryo, Laura; Bhagat, Tushar; Bhattacharyya, Sanchari; Ramachandra, Nandini; Bartenstein, Matthias; Pellagatti, Andrea; Boultwood, Jacqueline; Wickrema, Amittha; Yu, Yiting; Will, Britta; Wei, Sheng; Steidl, Ulrich; Verma, Amit

    2015-05-14

    Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Novel therapeutic targets against preleukemic stem cells need to be identified for potentially curative strategies. We conducted parallel transcriptional analysis of highly fractionated stem and progenitor populations in MDS, AML, and control samples and found interleukin 8 (IL8) to be consistently overexpressed in patient samples. The receptor for IL8, CXCR2, was also significantly increased in MDS CD34(+) cells from a large clinical cohort and was predictive of increased transfusion dependence. High CXCR2 expression was also an adverse prognostic factor in The Cancer Genome Atlas AML cohort, further pointing to the critical role of the IL8-CXCR2 axis in AML/MDS. Functionally, CXCR2 inhibition by knockdown and pharmacologic approaches led to a significant reduction in proliferation in several leukemic cell lines and primary MDS/AML samples via induction of G0/G1 cell cycle arrest. Importantly, inhibition of CXCR2 selectively inhibited immature hematopoietic stem cells from MDS/AML samples without an effect on healthy controls. CXCR2 knockdown also impaired leukemic growth in vivo. Together, these studies demonstrate that the IL8 receptor CXCR2 is an adverse prognostic factor in MDS/AML and is a potential therapeutic target against immature leukemic stem cell-enriched cell fractions in MDS and AML. © 2015 by The American Society of Hematology.

  19. Iterative Cellular Screening System for Nanoparticle Safety Testing

    Directory of Open Access Journals (Sweden)

    Franziska Sambale

    2015-01-01

    Full Text Available Nanoparticles have the potential to exhibit risks to human beings and to the environment; due to the wide applications of nanoproducts, extensive risk management must not be neglected. Therefore, we have constructed a cell-based, iterative screening system to examine a variety of nanoproducts concerning their toxicity during development. The sensitivity and application of various cell-based methods were discussed and proven by applying the screening to two different nanoparticles: zinc oxide and titanium dioxide nanoparticles. They were used as benchmarks to set up our methods and to examine their effects on mammalian cell lines. Different biological processes such as cell viability, gene expression of interleukin-8 and heat shock protein 70, as well as morphology changes were investigated. Within our screening system, both nanoparticle suspensions and coatings can be tested. Electric cell impedance measurements revealed to be a good method for online monitoring of cellular behavior. The implementation of three-dimensional cell culture is essential to better mimic in vivo conditions. In conclusion, our screening system is highly efficient, cost minimizing, and reduces the need for animal studies.

  20. IL-8 is upregulated in cervical cancer tissues and is associated with the proliferation and migration of HeLa cervical cancer cells.

    Science.gov (United States)

    Jia, Linlin; Li, Fengying; Shao, Mingliang; Zhang, Wei; Zhang, Chunbin; Zhao, Xiaolian; Luan, Haiyan; Qi, Yaling; Zhang, Pengxia; Liang, Lichun; Jia, Xiuyue; Zhang, Kun; Lu, Yan; Yang, Zhe; Zhu, Xiulin; Zhang, Qi; Du, Jiwei; Wang, Weiqun

    2018-01-01

    Interleukin-8 (IL-8) serves an important function in chronic inflammation and cancer development; however, the underlying molecular mechanism(s) of IL-8 in uterine cervical cancer remains unclear. The present study investigated whether IL-8 and its receptors [IL-8 receptor (IL-8R)A and IL-8RB] contributed to the proliferative and migratory abilities of HeLa cervical cancer cells, and also investigated the potential underlying molecular mechanisms. Results demonstrated that IL-8 and its receptors were detected in HeLa cells, and levels of IL-8RA were significantly increased compared with those of IL-8RB. Furthermore, the level of IL-8 in cervical cancer tissues was significantly increased compared with that in normal uterine cervical tissues, and migratory and proliferative efficiencies of HeLa cells treated with exogenous IL-8 were increased, compared with untreated HeLa cells. In addition, exogenous IL-8 was able to downregulate endocytic adaptor protein (NUMB), and upregulate IL-8RA, IL-8RB and extracellular signal-regulated protein kinases (ERKs) expression levels in HeLa cells. Results suggest that IL-8 and its receptors were associated with the tumorigenesis of uterine cervical cancer, and exogenous IL-8 promotes the carcinogenic potential of HeLa cells by increasing the expression levels of IL-8RA, IL-8RB and ERK, and decreasing the expression level of NUMB.

  1. Natural killer cell activation distinguishes Mycobacterium tuberculosis-mediated immune reconstitution syndrome from chronic HIV and HIV/MTB coinfection.

    Science.gov (United States)

    Conradie, Francesca; Foulkes, Andrea S; Ive, Prudence; Yin, Xiangfan; Roussos, Katerina; Glencross, Deborah K; Lawrie, Denise; Stevens, Wendy; Montaner, Luis J; Sanne, Ian; Azzoni, Livio

    2011-11-01

    With increased access to antiretroviral treatment (ART), immune reconstitution inflammatory syndrome (IRIS) in Mycobacterium tuberculosis (MTB)-infected populations remains a clinical challenge. We studied a cross-sectional cohort of HIV-infected subjects in Johannesburg (South Africa) to help define the immune correlates that best distinguish IRIS from ongoing MTB cases. We studied HIV+ subjects developing MTB-related unmasking tuberculosis-related immune reconstitution inflammatory syndrome (uTB-IRIS) after ART initiation; control groups were subjects with HIV and HIV/tuberculosis-coinfected subjects with comparable ART treatment. Testing was conducted with whole blood-based 4-color flow cytometry and plasma-based Luminex cytokine assessment. Natural killer cell activation, C-reactive protein, and interleukin 8 serum concentration were significantly higher in uTB-IRIS subjects compared with both control groups. In addition, all MTB-coinfected subjects, independent of clinical presentation, had higher neutrophils and T-cell activation, together with lower lymphocytes, CD4⁺ T-cell, and myeloid dendritic cell counts. Using conditional inference tree analysis, we show that elevated natural killer cell activation in combination with lymphocyte count characterizes the immunological profile of uTB-IRIS. Our results support a role for innate immune effectors in the immunopathogenesis of unmasking MTB-related IRIS and identify new immune parameters defining this pathology.

  2. Characterization of antibodies against ferret immunoglobulins, cytokines and CD markers

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Aasted, Bent

    2009-01-01

    Ferret IgG and IgM were purified from normal serum, while ferret IgA was purified from bile. The estimated molecular weights of the immunoglobulin gamma, alpha and mu heavy chains were found to be 54 kDa, 69 kDa and 83 kDa, respectively. For immunological (ELISA) quantification of ferret...... immunoglobulins, we identified and characterized polyclonal antibodies towards ferret IgG, IgM and IgA. We also identified 22 monoclonal antibodies (mAbs) raised mostly against human CD markers which cross-reacted with ferret leukocytes. These antibodies were originally specific against human CD8, CD9, CD14, CD18......, CD25, CD29, CD32, CD44, CD61, CD71, CD79b, CD88, CD104, CD172a and mink CD3. Finally, we identified 4 cross-reacting mAbs with specificities against ferret interferon-gamma, TNF-alpha, interleukin-4 and interleukin-8....

  3. Characterization of pneumonia due to Streptococcus equi subsp. zooepidemicus in dogs.

    Science.gov (United States)

    Priestnall, Simon L; Erles, Kerstin; Brooks, Harriet W; Cardwell, Jacqueline M; Waller, Andrew S; Paillot, Romain; Robinson, Carl; Darby, Alistair C; Holden, Matthew T G; Schöniger, Sandra

    2010-11-01

    Streptococcus equi subsp. zooepidemicus has been linked to cases of acute fatal pneumonia in dogs in several countries. Outbreaks can occur in kenneled dog populations and result in significant levels of morbidity and mortality. This highly contagious disease is characterized by the sudden onset of clinical signs, including pyrexia, dyspnea, and hemorrhagic nasal discharge. The pathogenesis of S. equi subsp. zooepidemicus infection in dogs is poorly understood. This study systematically characterized the histopathological changes in the lungs of 39 dogs from a large rehoming shelter in London, United Kingdom; the dogs were infected with S. equi subsp. zooepidemicus. An objective scoring system demonstrated that S. equi subsp. zooepidemicus caused pneumonia in 26/39 (66.7%) dogs, and most of these dogs (17/26 [65.4%]) were classified as severe fibrino-suppurative, necrotizing, and hemorrhagic. Three recently described superantigen genes (szeF, szeN, and szeP) were detected by PCR in 17/47 (36.2%) of the S. equi subsp. zooepidemicus isolates; however, there was no association between the presence of these genes and the histopathological score. The lungs of S. equi subsp. zooepidemicus-infected dogs with severe respiratory signs and lung pathology did however have significantly higher mRNA levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 8 (IL-8) than in uninfected controls, suggesting a role for an exuberant host immune response in the pathogenesis of this disease.

  4. Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models

    Directory of Open Access Journals (Sweden)

    Tania Rivera-Hernandez

    2016-06-01

    Full Text Available Group A Streptococcus (GAS is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i streptolysin O (SLO, interleukin 8 (IL-8 protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP], group A streptococcal C5a peptidase (SCPA, arginine deiminase (ADI, and trigger factor (TF; (ii the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a “gold standard” for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model.

  5. Toll-like receptor 2 (TLR2) mediates intracellular signalling in human keratinocytes in response to Malassezia furfur.

    Science.gov (United States)

    Baroni, Adone; Orlando, Manuela; Donnarumma, Giovanna; Farro, Pietro; Iovene, Maria Rosaria; Tufano, Maria Antonietta; Buommino, Elisabetta

    2006-01-01

    Toll-like receptors (TLRs) are crucial players in the innate immune response to microbial invaders. The lipophilic yeast Malassezia furfur has been implicated in the triggering of scalp lesions in psoriasis. The aim of the present study was to assess the role of TLRs in the defence against M. furfur infection. The expression of the myeloid differentiation factor 88 (MyD88) gene, which is involved in the signalling pathway of many TLRs, was also analysed. In addition, a possible correlation of antimicrobial peptides of the beta-defensin family to TLRs was tested. Human keratinocytes infected with M. furfur and a variety of M. furfur-positive psoriatic skin biopsies were analysed by RT-PCR, for TLRs, MyD88, human beta-defensin 2 (HBD-2), HBD-3 and interleukin-8 (IL-8) mRNA expression. When keratinocytes were infected with M. furfur, an up-regulation for TLR2, MyD88, HBD-2, HBD-3 and IL-8 mRNA was demonstrated, compared to the untreated cells. The same results were obtained when psoriatic skin biopsies were analysed. The M. furfur-induced increase in HBD-2 and IL-8 gene expression is inhibited by anti-TLR2 neutralising antibodies, suggesting that TLR2 is involved in the M. furfur-induced expression of these molecules. These findings suggest the importance of TLRs in skin protection against fungi and the importance of keratinocytes as a component of innate immunity.

  6. Jinwei Tang modulates HDAC2 expression in a rat model of COPD.

    Science.gov (United States)

    Wu, Jianjun; Li, Xin; Qin, Yang; Cheng, Juan; Hao, Gaimei; Jin, Ruifeng; Zhu, Chenjun

    2018-03-01

    The aim of the present study was to investigate the effect of a Traditional Chinese Herbal Medicine (TCHM), named Jinwei Tang on histone deacetylase 2 (HDAC2) and its role in the regulation of corticosteroid resistance in a rat model of chronic obstructive pulmonary disease (COPD). Male Wistar rats were divided into five groups (each n=10): COPD group, established by the intratracheal instillation of lipopolysaccharide and passive smoke exposure, and control, budesonide, theophylline + budesonide and Jinwei Tang + budesonide groups. Lung function was measured, lung tissue histopathology was examined and HDAC2 expression in the lung was assessed by immunohistochemistry. In addition, protein levels of interleukin-8 (IL-8), tumor necrosis factor (TNF)-α and HDAC2 in lung homogenate were quantified by ELISA. The rat COPD model exhibited alterations of the ratio of forced expiratory volume in 0.2 sec (FEV 0.2 ) to the forced vital capacity, FEV 0.2 , dynamic compliance and airway resistance. HDAC2 expression was markedly reduced in the lung tissue of the COPD group compared with the control group, and treatment with Jinwei Tang + budesonide or theophylline + budesonide resulted in significant attenuation of the reduction of HDAC2 expression in the lungs (PTang + budesonide and theophylline + budesonide groups, IL-8 and TNF-α expression was significantly decreased (PTang modulates airway inflammation and may enhance the anti-inflammatory effect of glucocorticoid through the upregulation of HADC2 expression in a rat model of COPD.

  7. Immune disorders induced by exposure to pyrethroid insecticides

    Directory of Open Access Journals (Sweden)

    Justyna Skolarczyk

    2017-06-01

    Full Text Available Pyrethroids are biocides, which belong to the third generation of insecticides. They are used as biocides, insecticides and medicines. These agents react selectively, because they are less harmful to birds and mammals (due to poor intestinal absorption and rapid detoxification in the body of homeothermic organisms and they are poisonous for fish and insects.The aim of the article is to present the current state of knowledge on the effects of pyrethroids on the immune system based on the latest scientific research.The mechanism of action of pyrethroids include the delaying closure of voltage- sensitive sodium and chloride channels (including GABA- dependent channels. These compounds are neurotoxic.Studies have shown that they cause numerous immune disorders contributing to lowering of immunity in humans and animals. Exposure to pyrethroids can cause inhibition of proliferation of peripheral blood leukocytes and reducing the concentration of IgG immunolgobulines. They also cause reduced macrophages and decrease in interleukin 2 (IL-2, interleukin 8 (IL-8, interleukin 12p70 (IL-12p70, and interferon γ (IFN-γ. Some of these compounds cause increase of liver weight and increase of bone marrow cellularity, and may induce apoptosis of the thymus. Pyrethroids can cause allergies and asthma. Their immunosuppressive effects can impair host resistance against infections. Exposure to these compounds can also contribute to induction of the cancer, especially in patients with impaired immune function.

  8. Association between Asymmetric Dimethylarginine and Pentosidine in Dialysis Effluent of Peritoneal Dialysis Patients -A possible intraperitoneal crosstalk between asymmetric dimethylarginine and advanced glycation end products in peritoneal dialysis patients.

    Science.gov (United States)

    Ishida, Mari; Kakuta, Takatoshi; Miyakogawa, Takayo; Tatsumi, Ryoko; Matsumoto, Chiemi; Fukagawa, Masafumi

    2016-06-20

    Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase. Elevated serum ADMA concentration is associated with impaired vascular endothelial function. We examined the relationships of ADMA with pentosidine, a representative advanced glycation end product, cytokines and the markers of peritoneal inflammation, damage and repair in dialysate effluent of peritoneal dialysis patients. Study design was cross-sectional. Twenty-eight peritoneal dialysis patients who were ≥ 18 years of age, had been on peritoneal dialysis for at least 3 months and had no history of renal transplantation were enrolled. Dialysis effluent and blood were sampled after 8 hours of peritoneal dialysis. Concentrations of ADMA, pentosidine, cytokines and the markers of peritoneal inflammation, damage and repair were determined in dialysis effluent. Blood samples were analyzed for routine laboratory parameters. The effluent ADMA level had a significant correlation with effluent pentosidine concentration (R=0.511, P=0.005), but not with interleukin-6, interleukin-8, transforming growth factor-α, hyaluronic acid, cancer antigen 125 or fibrinogen/fibrin degradation products. In the light of available evidence, our results suggest that AGEs generated during dialysate dwelling alters ADMA metabolism in the peritoneal tissues, leading to ADMA accumulation in the peritoneal cavity.

  9. Subfractions of enamel matrix derivative differentially influence cytokine secretion from human oral fibroblasts.

    Science.gov (United States)

    Villa, Oscar; Brookes, Steven J; Thiede, Bernd; Heijl, Lars; Lyngstadaas, Staale P; Reseland, Janne E

    2015-01-01

    Enamel matrix derivative is used to promote periodontal regeneration during the corrective phase of the treatment of periodontal defects. Our main goal was to analyze the bioactivity of different molecular weight fractions of enamel matrix derivative. Enamel matrix derivative, a complex mixture of proteins, was separated into 13 fractions using size-exclusion chromatography and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and liquid chromatography-electrospray ionization-tandem mass spectrometry. Human periodontal ligament fibroblasts were treated with either enamel matrix derivative or the different fractions. Proliferation and cytokine secretion to the cell culture medium were measured and compared to untreated cells. The liquid chromatography-electrospray ionization-tandem mass spectrometry analyses revealed that the most abundant peptides were amelogenin and leucine-rich amelogenin peptide related. The fractions containing proteins above 20 kDa induced an increase in vascular endothelial growth factor and interleukin-6 secretion, whereas lower molecular weight fractions enhanced proliferation and secretion of interleukin-8 and monocyte chemoattractant protein-1 and reduced interleukin-4 release. The various molecular components in the enamel matrix derivative formulation might contribute to reported effects on tissue regeneration through their influence on vascularization, the immune response, and chemotaxis.

  10. The physiological stress response to high-intensity sprint exercise following the ingestion of sodium bicarbonate.

    Science.gov (United States)

    Peart, Daniel J; Kirk, Richard J; Hillman, Angela R; Madden, Leigh A; Siegler, Jason C; Vince, Rebecca V

    2013-01-01

    The purpose of this study was to investigate the effects of pre-exercise alkalosis on the physiological stress response to high-intensity exercise. Seven physically active males (age 22 ± 3 years, height 1.82 ± 0.06 m, mass 81.3 ± 8.4 kg and peak power output 300 ± 22 W) performed a repeated sprint cycle exercise following a dose of 0.3 g kg(-1) body mass of sodium bicarbonate (NaHCO(3)) (BICARB), or a placebo of 0.045 g kg(-1) body mass of sodium chloride (PLAC). Monocyte-expressed heat shock protein 72 (HSP72) and plasma thiobarbituric acid reactive substances (TBARS) were significantly attenuated in BICARB compared to PLAC (p = 0.04 and p = 0.039, respectively), however total anti-oxidant capacity, the ratio of oxidised to total glutathione, cortisol, interleukin 6 and interleukin 8 were not significantly induced by the exercise. In conclusion, monocyte-expressed HSP72 is significantly increased following high-intensity anaerobic exercise, and its attenuation following such exercise with the ingestion of NaHCO(3) is unlikely to be due to a decreased oxidative stress.

  11. The IL-8 Protease SpyCEP/ScpC of Group A Streptococcus Promotes Resistance to Neutrophil Killing

    Science.gov (United States)

    Zinkernagel, Annelies S.; Timmer, Anjuli M.; Pence, Morgan A.; Locke, Jeffrey B.; Buchanan, John T.; Turner, Claire E.; Mishalian, Inbal; Sriskandan, Shiranee; Hanski, Emanuel; Nizet, Victor

    2009-01-01

    SUMMARY Interleukin-8 (IL-8) promotes neutrophil-mediated host defense through its chemoattractant and immunostimulatory activities. The Group A Streptococcus (GAS) protease SpyCEP (also called ScpC) cleaves IL-8, and SpyCEP expression is strongly upregulated in vivo in the M1T1 GAS strains associated with life-threatening systemic disease including necrotizing fasciitis. Coupling allelic replacement with heterologous gene expression, we show that SpyCEP is necessary and sufficient for IL-8 degradation. SpyCEP decreased IL-8-dependent neutrophil endothelial transmigration and bacterial killing, the latter by reducing neutrophil extracellular trap formation. The knockout mutant lacking SpyCEP was attenuated for virulence in murine infection models, and SpyCEP expression conferred protection to coinfecting bacteria. We also show that the zoonotic pathogen Streptococcus iniae possesses a functional homolog of SpyCEP (Cepl) that cleaves IL-8, promotes neutrophil resistance, and contributes to virulence. By inactivating the multifunctional host defense peptide IL-8, the SpyCEP protease impairs neutrophil clearance mechanisms, contributing to the pathogenesis of invasive streptococcal infection. PMID:18692776

  12. How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound Repair.

    Science.gov (United States)

    Gál, Peter; Varinská, Lenka; Fáber, Lenka; Novák, Štepán; Szabo, Pavol; Mitrengová, Petra; Mirossay, Andrej; Mučaji, Pavel; Smetana, Karel

    2017-10-26

    It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive scar formation. In the present review paper, we define key signaling molecules (growth factors, cytokines, chemokines, and galectins) involved in the formation of the tumor microenvironment that decrease overall survival and increase drug resistance in cancer suffering patients. Additional attention will also be given to show whether targeted modulation of these regulators promote tissue regeneration and wound management. Whole-genome transcriptome profiling, in vitro and animal experiments revealed that interleukin 6, interleukin 8, chemokine (C-X-C motif) ligand 1, galectin-1, and selected proteins of the extracellular matrix (e.g., fibronectin) do have similar regulation during wound healing and tumor growth. Published data demonstrate remarkable similarities between the tumor and wound microenvironments. Therefore, tailor made manipulation of cancer stroma can have important therapeutic consequences. Moreover, better understanding of cancer cell-stroma interaction can help to improve wound healing by supporting granulation tissue formation and process of reepithelization of extensive and chronic wounds as well as prevention of hypertrophic scars and formation of keloids.

  13. ALPK1 controls TIFA/TRAF6-dependent innate immunity against heptose-1,7-bisphosphate of gram-negative bacteria.

    Directory of Open Access Journals (Sweden)

    Milica Milivojevic

    2017-02-01

    Full Text Available During infection by invasive bacteria, epithelial cells contribute to innate immunity via the local secretion of inflammatory cytokines. These are directly produced by infected cells or by uninfected bystanders via connexin-dependent cell-cell communication. However, the cellular pathways underlying this process remain largely unknown. Here we perform a genome-wide RNA interference screen and identify TIFA and TRAF6 as central players of Shigella flexneri and Salmonella typhimurium-induced interleukin-8 expression. We show that threonine 9 and the forkhead-associated domain of TIFA are necessary for the oligomerization of TIFA in both infected and bystander cells. Subsequently, this process triggers TRAF6 oligomerization and NF-κB activation. We demonstrate that TIFA/TRAF6-dependent cytokine expression is induced by the bacterial metabolite heptose-1,7-bisphosphate (HBP. In addition, we identify alpha-kinase 1 (ALPK1 as the critical kinase responsible for TIFA oligomerization and IL-8 expression in response to infection with S. flexneri and S. typhimurium but also to Neisseria meningitidis. Altogether, these results clearly show that ALPK1 is a master regulator of innate immunity against both invasive and extracellular gram-negative bacteria.

  14. Classical swine fever virus infection modulates serum levels of INF-α, IL-8 and TNF-α in 6-month-old pigs.

    Science.gov (United States)

    von Rosen, T; Lohse, L; Nielsen, J; Uttenthal, Å

    2013-12-01

    Several studies have highlighted the important role of cytokines in disease development of classical swine fever virus (CSFV) infection. In the present study, we examined the kinetics of 7 porcine cytokines in serum from pigs infected with 3 different CSFV strains. Based on the clinical picture in 6-month-old Danish pigs, the strains used for inoculation were classified as being of low (Bergen), low to moderate (Eystrup) and moderate to high (Lithuania) virulence. The cytokines interferon-alpha (INF-α), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) showed increased levels after CSFV infection with more or less comparable course in the 3 groups. However, the cytokine level peaked with a 2-3 days delay in pigs infected with the low virulent strain compared to those infected with a moderately or highly virulent strain. These findings may indicate that INF-α, IL-8 and TNF-α are involved in the immune response during CSFV infection with strains of different virulence. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Silibinin inhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast cells.

    Science.gov (United States)

    Kim, Beom-Rak; Seo, Hye-Sook; Ku, Jin-Mo; Kim, Gyung-Jun; Jeon, Chan Yong; Park, Jong Hyeong; Jang, Bo-Hyoung; Park, Sun-Ju; Shin, Yong-Cheol; Ko, Seong-Gyu

    2013-11-01

    Silibinin is the major active molecule of silymarin, the mixture of flavonolignans extracted from Cirsium japonicum. It has been used for the treatment of hepatitis and inflammation-related diseases. In the present study, the effects of silibinin on allergic inflammation and its signaling were investigated in the induced human mast cells. Cell growth inhibition induced by silibinin was measured by MTS assay. Histamine release was measured by enzyme immunoassay. The tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) secreted protein levels and mRNA levels were measured by the ELISA assay and RT-PCR, respectively. The NF-κB promoter activity was examined by a luciferase assay. Silibinin suppressed the growth of HMC-1 cells and also reduced the production and mRNA expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8. Moreover, silibinin inhibited the nuclear translocation of nuclear factor (NF)-κB through inhibition of the phosphorylation of IκBα and suppressed NF-κB transcriptional activity in stimulated HMC-1 cells. Taken together, these results indicate that silibinin inhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast cells, suggesting that silibinin could be used for the treatment of mast cell-derived allergic inflammatory diseases.

  16. Knockdown of HIF-1α and IL-8 induced apoptosis of hepatocellular carcinoma triggers apoptosis of vascular endothelial cells.

    Science.gov (United States)

    Choi, Sung Hoon; Park, Jun Yong; Kang, Wonseok; Kim, Seung Up; Kim, Do Young; Ahn, Sang Hoon; Ro, Simon Wonsang; Han, Kwang-Hyub

    2016-01-01

    A local hypoxic microenvironment is one of the most important characteristics of solid tumors. Hypoxia inducible factor-1α (HIF-1α) and Interleukin-8 (IL-8) activate tumor survival from hypoxic-induced apoptosis in each pathway. This study aimed to evaluate whether knockdown of HIF-1α and IL-8 induced apoptosis of the hepatocellular carcinoma (HCC) and endothelial cell lines. HCC cell lines were infected with adenovirus-expressing shRNA for HIF-1α and IL-8 and maintained under hypoxic conditions (1% O2, 24 h). The expression levels of HIF-1α and both apoptotic and growth factors were examined by real-time quantitative PCR and western blot. We also investigated apoptosis by TUNEL assay (FACS and Immunofluorescence) and measured the concentration of cytochrome C. Inhibition of HIF-1α and IL-8 up-regulated the expression of apoptotic factors while downregulating anti-apoptotic factors simultaneously. Knockdown of HIF-1α and IL-8 increased the concentration of cytochrome C and enhanced DNA fragmentation in HCC cell lines. Moreover, culture supernatant collected from the knockdown of HIF-1α and IL-8 in HCC cell lines induced apoptosis in human umbilical vein endothelial cells under hypoxia, and the expression of variable apoptotic ligand increased from HCC cell lines, time-dependently. These data suggest that adenovirus-mediated knockdown of HIF-1α and IL-8 induced apoptosis in HCC cells and triggered apoptosis of vascular endothelial cells.

  17. Rat inhalation test with particles from biomass combustion and biomass co-firing exhaust

    Science.gov (United States)

    Bellmann, B.; Creutzenberg, O.; Ernst, H.; Muhle, H.

    2009-02-01

    The health effects of 6 different fly ash samples from biomass combustion plants (bark, wood chips, waste wood, and straw), and co-firing plants (coal, co-firing of coal and sawdust) were investigated in a 28-day nose-only inhalation study with Wistar WU rats. Respirable fractions of carbon black (Printex 90) and of titanium dioxide (Bayertitan T) were used as reference materials for positive and negative controls. The exposure was done 6 hours per day, 5 days per week at an aerosol concentration of 16 mg/m3. The MMAD of all fly ash samples and reference materials in the inhalation unit were in the range from 1.5 to 3 μm. The investigations focused predominantly on the analysis of inflammatory effects in the lungs of rats using bronchoalveolar lavage (BAL) and histopathology. Different parameters (percentage of polymorphonuclear neutrophils (PMN), interleukin-8 and interstitial inflammatory cell infiltration in the lung tissue) indicating inflammatory effects in the lung, showed a statistically significant increase in the groups exposed to carbon black (positive control), C1 (coal) and C1+BM4 (co-firing of coal and sawdust) fly ashes. Additionally, for the same groups a statistically significant increase of cell proliferation in the lung epithelium was detected. No significant effects were detected in the animal groups exposed to BM1 (bark), BM2 (wood chips), BM3 (waste wood), BM6 (straw) or titanium dioxide.

  18. Identification of peripheral inflammatory markers between normal control and Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Jo Sangmee

    2011-05-01

    Full Text Available Abstract Background Multiple pathogenic factors may contribute to the pathophysiology of Alzheimer's disease (AD. Peripheral blood markers have been used to assess biochemical changes associated with AD and mild cognitive impairment (MCI and involved in their pathophysiology. Methods Plasma samples and clinical data were obtained from participants in the Ansan Geriatric Study (AGE study. Plasma concentrations of four candidate biomarkers were measured in the normal control (NC, MCI, and AD group: interleukin-8 (IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1, and tumor necrosis factor-α (TNF-α. Body mass index (BMI, MMSE (Mini Mental State Examination, CDR(Clinical Dementia Rating score and homocystein level were recorded with social and demographic information. Results Total of 59 subjects were randomly selected for this analysis [NC (n = 21, MCI(n = 20 and AD(n = 18]. In demographic data, educational year was correlated with the diagnosis states (p p Conclusions Our study suggests the existence of an independent and negative relationship between plasma IL-8 levels and functional status in MCI and AD patients.

  19. Identification of peripheral inflammatory markers between normal control and Alzheimer's disease.

    Science.gov (United States)

    Kim, Sam-Moon; Song, Juhee; Kim, Seungwoo; Han, Changsu; Park, Moon Ho; Koh, Youngho; Jo, Sangmee Ahn; Kim, Young-Youl

    2011-05-12

    Multiple pathogenic factors may contribute to the pathophysiology of Alzheimer's disease (AD). Peripheral blood markers have been used to assess biochemical changes associated with AD and mild cognitive impairment (MCI) and involved in their pathophysiology. Plasma samples and clinical data were obtained from participants in the Ansan Geriatric Study (AGE study). Plasma concentrations of four candidate biomarkers were measured in the normal control (NC), MCI, and AD group: interleukin-8 (IL-8), IL-10, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α).Body mass index (BMI), MMSE (Mini Mental State Examination), CDR(Clinical Dementia Rating) score and homocystein level were recorded with social and demographic information. Total of 59 subjects were randomly selected for this analysis [NC (n = 21), MCI(n = 20) and AD(n = 18)]. In demographic data, educational year was correlated with the diagnosis states (p homocystein of the three groups, but no significant differences were found in each groups. The plasma IL-8 level was lower in MCI and AD patients compared with the normal control group (respectively, p < 0.0001). The MCI and AD patients had similar MCP-1, IL-10, and TNF-α level. Our study suggests the existence of an independent and negative relationship between plasma IL-8 levels and functional status in MCI and AD patients.

  20. Alzheimer's Disease-like Early-phase Brain Pathogenesis: Self-curing Amelioration of Neurodegeneration from Pro-inflammatory 'Wounding' to Anti-inflammatory 'Healing'.

    Science.gov (United States)

    He, Jiang; Liao, Tao; Zhong, Guo-Xin; Zhang, Ji-Da; Chen, Yan-Ping; Wang, Qi; Zeng, Qing-Ping

    2017-01-01

    The etiological initiators of neuroinflammation remain inconclusive, and effective interventions to block neurodegeneration are unavailable. Surprisingly, we found collagen II-combined complete Freund's adjuvant (CC) that usually induces rheumatoid arthritis (RA) also drives Alzheimer's disease (AD)-like neurodegeneration in mice. CC not only upregulates the cerebral pro-inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 8 (IL-8), but also downregulates the cerebral interleukin 10 (IL-10), an anti-inflammatory cytokine, and tyrosine hydroxylase (TH), a ratelimiting enzyme for biosynthesis of the anti-inflammatory neurotransmitter dopamine. In contrast, electroacupuncture (EA) elevates TNF-α/IL-8 and declines IL-10/TH at first, but declines TNF-α/IL-8 and elevates IL-10/TH later. Upon impact on mitochondrial biogenesis, ubiquitination, and autophagy, EA firstly potentates but secondly attenuates CC-triggered signaling cascades leading to oxidation, nitrosylation, hypoxia, and angiogenesis. Eventually, EA compromises neurodegeneration by decreasing amyloid- β peptide (Aβ) and phosphorylated tau protein (p-tau), and also rectifies neuronal dysfunctions by increasing the cholinergic neurotransmitter acetylcholine (Ach) and its rate-limiting biosynthetic enzyme choline acetyltransferase (ChAT). Conclusively, EA initially aggravates and subsequently ameliorates CC-evoked AD-like earlyphase brain pathogenesis via conversion from pro-inflammatory microglia to anti-inflammatory microglia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-alpha in monocyte-derived macrophages.

    Science.gov (United States)

    Kim, Sung-Jo

    2010-06-01

    In addition to regulating body weight, leptin is also recognized for its role in the regulation of immune function and inflammation. The purpose of this study was to investigate the effect of leptin on Prevotella (P.) intermedia lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production in differentiated THP-1 cells, a human monocytic cell line. LPS from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. The amount of TNF-alpha and interleukin-8 secreted into the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha and Ob-R mRNA expression levels were determined by semi-quantitative reverse transcription-polymerase chain reaction analysis. Leptin enhanced P. intermedia LPS-induced TNF-alpha production in a dose-dependent manner. Leptin modulated P. intermedia LPS-induced TNF-alpha expression predominantly at the transcriptional level. Effect of leptin on P. intermedia LPS-induced TNF-alpha production was not mediated by the leptin receptor. The ability of leptin to enhance P. intermedia LPS-induced TNF-alpha production may be important in the establishment of chronic lesion accompanied by osseous tissue destruction observed in inflammatory periodontal disease.

  2. Monocytic Cell Activation by Nonendotoxic Glycoprotein from Prevotella intermedia ATCC 25611 Is Mediated by Toll-Like Receptor 2

    Science.gov (United States)

    Sugawara, Shunji; Yang, Shuhua; Iki, Koichi; Hatakeyama, Junko; Tamai, Riyoko; Takeuchi, Osamu; Akashi, Sachiko; Espevik, Terje; Akira, Shizuo; Takada, Haruhiko

    2001-01-01

    Lipopolysaccharide (LPS) preparations from gram-negative black-pigmented bacteria such as Porphyromonas gingivalis and Prevotella intermedia activate cells from non-LPS-responsive C3H/HeJ mice, but it is still unclear whether this activity is due to the unique structure of LPS or to a minor component(s) responsible for the activity in the preparation. A nonendotoxic glycoprotein with bioactivity against cells from C3H/HeJ mice was purified from a hot phenol-water extract of P. intermedia ATCC 25611 and designated Prevotella glycoprotein (PGP). Treatment of human monocytic THP-1 cells with 22-oxyacalcitriol (OCT) induced maturation and marked expression of CD14 on the cells, but the cells constitutively expressed Toll-like receptor 2 (TLR2) and TLR4 on the cells irrespective of the treatment. PGP induced a high level of interleukin-8 production at doses of 100 ng/ml and higher in OCT-treated THP-1 cells compared with Salmonella LPS, and the production was significantly inhibited by anti-CD14 and anti-TLR2 but not anti-TLR4 antibodies. Consistent with this, TLR2-deficient murine macrophages did not respond to PGP. It was also shown that PGP activity on the THP-1 cells was LPS-binding protein dependent and was inhibited by a synthetic lipid A precursor IVA. These results indicate that PGP activates monocytic cells in a CD14- and TLR2-dependent manner. PMID:11447173

  3. Chemokines and immunity

    Science.gov (United States)

    Palomino, Diana Carolina Torres; Marti, Luciana Cavalheiro

    2015-01-01

    Chemokines are a large family of small cytokines and generally have low molecular weight ranging from 7 to 15kDa. Chemokines and their receptors are able to control the migration and residence of all immune cells. Some chemokines are considered pro-inflammatory, and their release can be induced during an immune response at a site of infection, while others are considered homeostatic and are involved in controlling of cells migration during tissue development or maintenance. The physiologic importance of this family of mediators is resulting from their specificity − members of the chemokine family induce recruitment of well-defined leukocyte subsets. There are two major chemokine sub-families based upon cysteine residues position: CXC and CC. As a general rule, members of the CXC chemokines are chemotactic for neutrophils, and CC chemokines are chemotactic for monocytes and sub-set of lymphocytes, although there are some exceptions. This review discusses the potential role of chemokines in inflammation focusing on the two best-characterized chemokines: monocyte chemoattractant protein-1, a CC chemokine, and interleukin-8, a member of the CXC chemokine sub-family. PMID:26466066

  4. The Multifaceted Responses of Primary Human Astrocytes and Brain Microvascular Endothelial Cells to the Lyme Disease Spirochete, Borrelia Burgdorferi

    Directory of Open Access Journals (Sweden)

    Catherine A. Brissette

    2013-07-01

    Full Text Available The vector-borne pathogen, Borrelia burgdorferi, causes a multi-system disorder including neurological complications. These neurological disorders, collectively termed neuroborreliosis, can occur in up to 15% of untreated patients. The neurological symptoms are probably a result of a glial-driven, host inflammatory response to the bacterium. However, the specific contributions of individual glial and other support cell types to the pathogenesis of neuroborreliosis are relatively unexplored. The goal of this project was to characterize specific astrocyte and endothelial cell responses to B. burgdorferi. Primary human astrocytes and primary HBMEC (human brain microvascular endothelial cells were incubated with B. burgdorferi over a 72-h period and the transcriptional responses to the bacterium were analyzed by real-time PCR arrays. There was a robust increase in several surveyed chemokine and related genes, including IL (interleukin-8, for both primary astrocytes and HBMEC. Array results were confirmed with individual sets of PCR primers. The production of specific chemokines by both astrocytes and HBMEC in response to B. burgdorferi, including IL-8, CXCL-1, and CXCL-10, were confirmed by ELISA. These results demonstrate that primary astrocytes and HBMEC respond to virulent B. burgdorferi by producing a number of chemokines. These data suggest that infiltrating phagocytic cells, particularly neutrophils, attracted by chemokines expressed at the BBB (blood–brain barrier may be important contributors to the early inflammatory events associated with neuroborreliosis.

  5. Expression of functional toll-like receptor-2 and -4 on alveolar epithelial cells.

    Science.gov (United States)

    Armstrong, Lynne; Medford, Andrew R L; Uppington, Kay M; Robertson, John; Witherden, Ian R; Tetley, Teresa D; Millar, Ann B

    2004-08-01

    The recognition of potentially harmful microorganisms involves the specific recognition of pathogen-associated molecular patterns (PAMPs) and the family of Toll-like receptors (TLRs) is known to play a central role in this process. TLR-4 is the major recognition receptor for lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, whereas TLR-2 responds to bacterial products from gram-positive organisms. Although resident alveolar macrophages are the first line of defense against microbial attack, it is now understood that the alveolar epithelium also plays a pivotal role in the innate immunity of the lung. The purpose of the current study was to determine whether human primary type II alveolar epithelial cells (ATII) express functional TLR-2 and TLR-4 and how they may be regulated by inflammatory mediators. We have used reverse transcriptase-polymerase chain reaction and flow cytometry to determine basal and inducible expression on ATII. We have used highly purified preparations of the gram-positive bacterial product lipoteichoic acid (LTA) and LPS to look at the functional consequences of TLR-2 and TLR-4 ligation, respectively, in terms of interleukin-8 release. We have shown that human primary ATII cells express mRNA and protein for both TLR-2 and TLR-4, which can be modulated by incubation with LPS and tumor necrosis factor. Furthermore, we have demonstrated that these receptors are functional. This suggests that ATII have the potential to contribute significantly to the host defense of the human alveolus against bacteria.

  6. Identification and expression analysis of two pro-inflammatory cytokines, TNF-α and IL-8, in cobia (Rachycentron canadum L.) in response to Streptococcus dysgalactiae infection.

    Science.gov (United States)

    Nguyen, Thuy Thi Thu; Nguyen, Hai Trong; Wang, Pei-Chyi; Chen, Shih-Chu

    2017-08-01

    Tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8/CXCL8) play pivotal roles in mediating inflammatory responses to invading pathogens. In this study, we identified and analyzed expressions of cobia TNF-α and IL-8 during Streptococcus dysgalactiae infection. The cloned cDNA transcript of cobia TNF-α comprised of 1281 base pairs (bp), with a 774 bp open reading frame (ORF) encoding 257 amino acids. The deduced amino acid sequence of cobia TNF-α showed a close relationship (84% similarity) with TNF-α of yellowtail amberjack. The cloned IL-8 cDNA sequence was 828 bp long, including a 300-bp ORF encoding 99 amino acids. The deduced amino acid sequence of cobia IL-8 shared 90% identity with IL-8 of striped trumpeter. Cobia challenged with a virulent S. dysgalactiae strain displayed an early significant up-regulation of TNF-α and IL-8 in head kidney, liver, and spleen. Notably, IL-8 expression level increased dramatically in the liver at the severe stage of infection (72 h). In conclusion, a better understanding of TNF-α and IL-8 allows more detailed investigation of immune responses in cobia and furthers study on controlling the infectious disease caused by S. dysgalactiae. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Acute effects of cigarette smoking on inflammation in healthy intermittent smokers

    Directory of Open Access Journals (Sweden)

    Vonk Judith M

    2005-03-01

    Full Text Available Abstract Background Chronic smoking is the main risk factor for chronic obstructive pulmonary disease. Knowledge on the response to the initial smoke exposures might enhance the understanding of changes due to chronic smoking, since repetitive acute smoke effects may cumulate and lead to irreversible lung damage. Methods We investigated acute effects of smoking on inflammation in 16 healthy intermittent smokers in an open randomised cross-over study. We compared effects of smoking of two cigarettes on inflammatory markers in exhaled air, induced sputum, blood and urine at 0, 1, 3, 6, 12, 24, 48, 96 and 192 hours and outcomes without smoking. All sputum and blood parameters were log transformed and analysed using a linear mixed effect model. Results Significant findings were: Smoking increased exhaled carbon monoxide between 0 and 1 hour, and induced a greater decrease in blood eosinophils and sputum lymphocytes between 0 and 3 hours compared to non-smoking. Compared to non-smoking, smoking induced a greater interleukin-8 release from stimulated blood cells between 0 and 3 hours, and a greater increase in sputum lymphocytes and neutrophils between 3 and 12 hours. Conclusion We conclude that besides an increase in inflammation, as known from chronic smoking, there is also a suppressive effect of smoking two cigarettes on particular inflammatory parameters.

  8. Cigarette smoke induces IL-8, but inhibits eotaxin and RANTES release from airway smooth muscle

    Directory of Open Access Journals (Sweden)

    John Matthias

    2005-07-01

    Full Text Available Abstract Background Cigarette smoke is the leading risk factor for the development of chronic obstructive pulmonary disease (COPD an inflammatory condition characterised by neutrophilic inflammation and release of proinflammatory mediators such as interleukin-8 (IL-8. Human airway smooth muscle cells (HASMC are a source of proinflammatory cytokines and chemokines. We investigated whether cigarette smoke could directly induce the release of chemokines from HASMC. Methods HASMC in primary culture were exposed to cigarette smoke extract (CSE with or without TNFα. Chemokines were measured by enzyme-linked immunosorbent assay (ELISA and gene expression by real time polymerase chain reaction (PCR. Data were analysed using one-way analysis of variance (ANOVA followed by Bonferroni's t test Results CSE (5, 10 and 15% induced IL-8 release and expression without effect on eotaxin or RANTES release. At 20%, there was less IL-8 release. TNFα enhanced CSE-induced IL-8 release and expression. However, CSE (5–30% inhibited TNFα-induced eotaxin and RANTES production. The effects of CSE on IL-8 release were inhibited by glutathione (GSH and associated with the induction of the oxidant sensing protein, heme oxygenase-1. Conclusion Cigarette smoke may directly cause the release of IL-8 from HASMC, an effect enhanced by TNF-α which is overexpressed in COPD. Inhibition of eotaxin and RANTES by cigarette smoke is consistent with the predominant neutrophilic but not eosinophilic inflammation found in COPD.

  9. Cigarette Smoke Dampens Anti-viral Signaling in Small Airway Epithelial Cells by Disrupting TLR3 Cleavage.

    Science.gov (United States)

    Duffney, Parker F; McCarthy, Claire E; Nogales, Aitor; Thatcher, Thomas H; Martinez-Sobrido, Luis; Phipps, Richard P; Sime, Patricia J

    2017-12-14

    Cigarette smokers and people exposed to secondhand smoke are at an increased risk for pulmonary viral infections, yet the mechanism responsible for this heightened susceptibility is not understood. To understand the effect of cigarette smoke on susceptibility to viral infection we used an air-liquid interface culture system, and exposed primary human small airway epithelial cells (SAEC) to whole cigarette smoke followed by treatment with the viral mimetic polyinosinic polycytidylic acid (poly I:C) or influenza A virus (IAV). We found that prior smoke exposure strongly inhibited production of pro-inflammatory (interleukin 6 and interleukin 8) and anti-viral (interferon gamma induced protein 10, IP-10 and interferons) mediators in SAECs in response to poly I:C and IAV infection. Impaired antiviral responses corresponded to increased infection with IAV. This was associated with a decrease in phosphorylation of the key antiviral transcription factor interferon response factor (IRF3). Here we found that cigarette smoke exposure inhibited activation of toll-like receptor (TLR) 3 by impairing TLR3 cleavage, which was required for downstream phosphorylation of IRF3 and production of IP-10. These results identify a novel mechanism by which cigarette smoke exposure impairs antiviral responses in lung epithelial cells, which may contribute to increased susceptibility to respiratory infections.

  10. Genetic and physical mapping of 2q35 in the region of NRAMP and IL8R genes: Identification of a polymorphic repeat in exon 2 of NRAMP

    Energy Technology Data Exchange (ETDEWEB)

    White, J.K.; Shaw, M.A.; Barton, C.H. [Addenbrooke`s Hospital, Cambridge (United Kingdom)] [and others

    1994-11-15

    Recent interest has focused on the region of conserved synteny between mouse chromosome 1 and human 2q33-q37, particularly over the region encoding the murine macrophage resistance gene Ity/Lsh/Bcg (candidate Nramp) and members of the Il8r interleukin-8 (IL8) receptor gene cluster. In this paper, identification of a restriction fragment length polymorphism in the Il8RB gene in 35 pedigrees previously typed for markers in the 2q33-37 interval provided evidence (lod scores > 3) for linkage between Il8RB and the 2q34-135 markers FN1, TNP1, VIL1, and DES. Physical mapping, using yeast artificial chromosomes isolated with VIL1, confirmed that IL8RA, IL8RB and the IL8RB pseudogene map within the NRAMP-VIL1 interval, with the physical distance (155 kb) from 5{prime} LSH to 3{prime} VIL1 representing {approx}3-fold that observed in the mouse. Partial sequencing of NRAMP confirmed the presence of the N-terminal proline/serine-rich putative SH3 binding domain in exon 2 of the human gene. Further analysis of Brazilian leprosy and visceral leishmaniasis pedigrees identified a rare second allele varying in a 9-nucleotide repeat motif of the exon 2 sequence but segregating independently of the disease phenotype. 38 refs., 4 figs., 3 tabs.

  11. Functional Analysis of Lactobacillus rhamnosus GG Pili in Relation to Adhesion and Immunomodulatory Interactions with Intestinal Epithelial Cells

    Science.gov (United States)

    Claes, Ingmar; Tytgat, Hanne L. P.; Verhoeven, Tine L. A.; Marien, Eyra; von Ossowski, Ingemar; Reunanen, Justus; Palva, Airi; de Vos, Willem M.; De Keersmaecker, Sigrid C. J.; Vanderleyden, Jos

    2012-01-01

    Lactobacillus rhamnosus GG, a probiotic with good survival capacity in the human gut, has well-documented adhesion properties and health effects. Recently, spaCBA-encoded pili that bind to human intestinal mucus were identified on its cell surface. Here, we report on the phenotypic analysis of a spaCBA pilus knockout mutant in comparison with the wild type and other adhesin mutants. The SpaCBA pilus of L. rhamnosus GG showed to be key for efficient adherence to the Caco-2 intestinal epithelial cell (IEC) line and biofilm formation. Moreover, the spaCBA mutant induces an elevated level of interleukin-8 (IL-8) mRNA in Caco-2 cells compared to the wild type, possibly involving an interaction of lipoteichoic acid with Toll-like receptor 2. In contrast, an L. rhamnosus GG mutant without exopolysaccharides but with an increased exposure of pili leads to the reduced expression of IL-8. Using Transwells to partition bacteria from Caco-2 cells, IL-8 induction is blocked completely regardless of whether wild-type or mutant L. rhamnosus GG cells are used. Taken together, our data suggest that L. rhamnosus GG SpaCBA pili, while promoting strong adhesive interactions with IECs, have a functional role in balancing IL-8 mRNA expression induced by surface molecules such as lipoteichoic acid. PMID:22020518

  12. Functional analysis of Lactobacillus rhamnosus GG pili in relation to adhesion and immunomodulatory interactions with intestinal epithelial cells.

    Science.gov (United States)

    Lebeer, Sarah; Claes, Ingmar; Tytgat, Hanne L P; Verhoeven, Tine L A; Marien, Eyra; von Ossowski, Ingemar; Reunanen, Justus; Palva, Airi; Vos, Willem M de; Keersmaecker, Sigrid C J De; Vanderleyden, Jos

    2012-01-01

    Lactobacillus rhamnosus GG, a probiotic with good survival capacity in the human gut, has well-documented adhesion properties and health effects. Recently, spaCBA-encoded pili that bind to human intestinal mucus were identified on its cell surface. Here, we report on the phenotypic analysis of a spaCBA pilus knockout mutant in comparison with the wild type and other adhesin mutants. The SpaCBA pilus of L. rhamnosus GG showed to be key for efficient adherence to the Caco-2 intestinal epithelial cell (IEC) line and biofilm formation. Moreover, the spaCBA mutant induces an elevated level of interleukin-8 (IL-8) mRNA in Caco-2 cells compared to the wild type, possibly involving an interaction of lipoteichoic acid with Toll-like receptor 2. In contrast, an L. rhamnosus GG mutant without exopolysaccharides but with an increased exposure of pili leads to the reduced expression of IL-8. Using Transwells to partition bacteria from Caco-2 cells, IL-8 induction is blocked completely regardless of whether wild-type or mutant L. rhamnosus GG cells are used. Taken together, our data suggest that L. rhamnosus GG SpaCBA pili, while promoting strong adhesive interactions with IECs, have a functional role in balancing IL-8 mRNA expression induced by surface molecules such as lipoteichoic acid.

  13. CD18-mediated adhesion is required for the induction of a proinflammatory phenotype in lung epithelial cells by mononuclear cell-derived extracellular vesicles.

    Science.gov (United States)

    Neri, Tommaso; Scalise, Valentina; Passalacqua, Ilaria; Giusti, Ilaria; Lombardi, Stefania; Balia, Cristina; D'Alessandro, Delfo; Berrettini, Stefano; Pedrinelli, Roberto; Paggiaro, Pierluigi; Dolo, Vincenza; Celi, Alessandro

    2018-04-01

    Extracellular vesicles are submicron vesicles that upregulate the synthesis of proinflammatory mediators by lung epithelial cells. We investigated whether these structures adhere to lung epithelial cells, and whether adhesion is a prerequisite for their proinflammatory activity. Extracellular vesicles were generated by stimulation of normal human mononuclear cells with the calcium ionophore A23187, and labelled with carboxyfluorescein diacetate succinimidyl ester. Adhesion of vesicles to monolayers of immortalized bronchial epithelial (16HBE) and alveolar (A549) cells was analyzed by fluorescence microscopy. The role of candidate adhesion receptors was evaluated with inhibitory monoclonal antibodies and soluble peptides. The synthesis of proinflammatory mediators was assessed by ELISA. Transmission electron microscopy confirmed the generation of closed vesicles with an approximate size range between 50 and 600 nm. Adhesion of extracellular vesicles to epithelial cells was upregulated upon stimulation of the latter with tumor necrosis factor-α. Adhesion was blocked by an anti-CD18 antibody, by peptides containing the sequence RGD and, to a lesser extent, by an antibody to ICAM-1. The same molecules also blocked the upregulation of the synthesis of interleukin-8 and monocyte chemotactic protein-1 induced by extracellular vesicles. CD18-mediated adhesion of extracellular vesicles is a prerequisite for their proinflammatory activity. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Evaluating cytoplasmic and nuclear levels of inflammatory cytokines in cancer cells by western blotting.

    Science.gov (United States)

    Gatla, Himavanth R; Singha, Bipradeb; Persaud, Valerie; Vancurova, Ivana

    2014-01-01

    Increased expression and cellular release of inflammatory cytokines, interleukin-8 (IL-8; CXCL8), and high mobility group box-1 (HMGB1) are associated with increased cell proliferation, angiogenesis, and metastasis during cancer progression. In prostate and ovarian cancer cells, increased levels of IL-8 and HMGB1 correlate with poor prognosis. We have recently shown that proteasome inhibition by bortezomib (BZ) specifically increases IL-8 release from metastatic prostate and ovarian cancer cells. In this chapter, we describe a protocol to analyze the cytoplasmic and nuclear levels of IL-8 and HMGB1 in prostate and ovarian cancer cells by western blotting. IL-8 is localized in the cytoplasm in both cell types, and its protein levels are significantly increased by BZ. In contrast, HMGB1 is localized in the nucleus, and BZ increases its nuclear levels only in ovarian cancer cells. The protocol includes isolation of cytoplasmic and nuclear extracts, followed by SDS electrophoresis and western blotting, and can be easily modified to analyze the cytoplasmic and nuclear cytokine levels in other cell types.

  15. Obstructive sleep apnea and inflammation.

    LENUS (Irish Health Repository)

    McNicholas, Walter T

    2012-02-01

    The pathogenesis of cardiovascular complications in obstructive sleep apnea syndrome (OSAS) is not fully understood but is likely multifactorial in origin. Inflammatory processes play an important role in the pathogenesis of atherosclerosis, and circulating levels of several markers of inflammation have been associated with future cardiovascular risk. These include cell adhesion molecules such as intercellular adhesion molecule-1 and selectins, cytokines such as tumour necrosis factor alpha and interleukin 6, chemokines such as interleukin 8, and C-reactive protein. There is also increasing evidence that inflammatory processes play an important role in the cardiovascular pathophysiology of OSAS and many of the inflammatory markers associated with cardiovascular risk have been reported as elevated in patients with OSAS. Furthermore, animal and cell culture studies have demonstrated preferential activation of inflammatory pathways by intermittent hypoxia, which is an integral feature of OSAS. The precise role of inflammation in the development of cardiovascular disease in OSAS requires further study, particularly the relationship with oxidative stress, metabolic dysfunction, and obesity.

  16. Exercise intensity, redox homeostasis and inflammation in type 2 diabetes mellitus.

    Science.gov (United States)

    Mallard, Alistair R; Hollekim-Strand, Siri Marte; Coombes, Jeff S; Ingul, Charlotte B

    2017-10-01

    To compare 12 weeks of exercise training at two intensities on oxidative stress, antioxidants and inflammatory biomarkers in patients with type 2 diabetes (T2D). Randomized trial. Thirty-six participants with T2D were randomized to complete either 12 weeks of treadmill based high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT), followed by 40 weeks of home-based training at the same intensities. Plasma inflammation, oxidative stress and antioxidant biomarkers (total F2-isoprostanes, protein carbonyls, total antioxidant capacity, glutathione peroxidase activity, interleukin-10, interleukin-6, interleukin-8 and TNF-α) were measured at baseline, 12-weeks and 1-year. There were no significant changes (p>0.05) in oxidative stress and inflammation biomarkers from baseline to 12-weeks in either intervention. A decrease in total antioxidant capacity in the MICT group from baseline to 1-year by 0.05mmol/L (p=0.05) was observed. There was a significant difference (p<0.05) when groups were separated by sex with females in the MICT group having a 22.1% (p<0.05) decrease in protein carbonyls from baseline to 1-year. HIIT and MICT had no acute effect on oxidative stress and inflammatory biomarkers in patients with T2D. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  17. Structure of a membrane-attack complex/perforin (MACPF) family protein from the human gut symbiont Bacteroides thetaiotaomicron

    International Nuclear Information System (INIS)

    Xu, Qingping; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Bakolitsa, Constantina; Cai, Xiaohui; Carlton, Dennis; Chen, Connie; Chiu, Hsiu-Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Ellrott, Kyle; Farr, Carol L.; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Kumar, Abhinav; Lam, Winnie W.; Marciano, David; Miller, Mitchell D.; Morse, Andrew T.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Puckett, Christina; Reyes, Ron; Tien, Henry J.; Trame, Christine B.; Bedem, Henry van den; Weekes, Dana; Wooten, Tiffany; Yeh, Andrew; Zhou, Jiadong; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    The crystal structure of a novel MACPF protein, which may play a role in the adaptation of commensal bacteria to host environments in the human gut, was determined and analyzed. Membrane-attack complex/perforin (MACPF) proteins are transmembrane pore-forming proteins that are important in both human immunity and the virulence of pathogens. Bacterial MACPFs are found in diverse bacterial species, including most human gut-associated Bacteroides species. The crystal structure of a bacterial MACPF-domain-containing protein BT-3439 (Bth-MACPF) from B. thetaiotaomicron, a predominant member of the mammalian intestinal microbiota, has been determined. Bth-MACPF contains a membrane-attack complex/perforin (MACPF) domain and two novel C-terminal domains that resemble ribonuclease H and interleukin 8, respectively. The entire protein adopts a flat crescent shape, characteristic of other MACPF proteins, that may be important for oligomerization. This Bth-MACPF structure provides new features and insights not observed in two previous MACPF structures. Genomic context analysis infers that Bth-MACPF may be involved in a novel protein-transport or nutrient-uptake system, suggesting an important role for these MACPF proteins, which were likely to have been inherited from eukaryotes via horizontal gene transfer, in the adaptation of commensal bacteria to the host environment

  18. Differential Effects of Planktonic and Biofilm MRSA on Human Fibroblasts

    Science.gov (United States)

    Kirker, Kelly R.; James, Garth A.; Fleckman, Philip; Olerud, John E.; Stewart, Philip S.

    2012-01-01

    Bacteria colonizing chronic wounds often exist as biofilms, yet their role in chronic wound pathogenesis remains unclear. Staphylococcus aureus biofilms induce apoptosis in dermal keratinocytes, and given that chronic wound biofilms also colonize dermal tissue, it is important to investigate the effects of bacterial biofilms on dermal fibroblasts. The effects of a predominant wound pathogen, methicillin-resistant S. aureus, on normal, human, dermal fibroblasts were examined in vitro. Cell culture medium was conditioned with equivalent numbers of either planktonic or biofilm methicillin-resistant S. aureus, and then fed to fibroblast cultures. Fibroblast response was evaluated using scratch, viability, and apoptosis assays. The results suggested that fibroblasts experience the same fate when exposed to the soluble products of either planktonic or biofilm methicillin-resistant S. aureus, namely limited migration followed by death. Enzyme-linked immunosorbent assays demonstrated that fibroblast production of cytokines, growth factors, and proteases were differentially affected by planktonic and biofilm-conditioned medium. Planktonic-conditioned medium induced more interleukin-6, interleukin-8, vascular endothelial growth factor, transforming growth factor-β1, heparin-bound epidermal growth factor, matrix metalloproteinase-1, and metalloproteinase-3 production in fibroblasts than the biofilm-conditioned medium. Biofilm-conditioned medium induced more tumor-necrosis factor-α production in fibroblasts compared to planktonic-conditioned medium, and suppressed metalloproteinase-3 production compared to controls. PMID:22332802

  19. Immune disorders induced by exposure to pyrethroid insecticides.

    Science.gov (United States)

    Skolarczyk, Justyna; Pekar, Joanna; Nieradko-Iwanicka, Barbara

    2017-06-08

    Pyrethroids are biocides, which belong to the third generation of insecticides. They are used as biocides, insecticides and medicines. These agents react selectively, because they are less harmful to birds and mammals (due to poor intestinal absorption and rapid detoxification in the body of homeothermic organisms) and they are poisonous for fish and insects. The aim of the article is to present the current state of knowledge on the effects of pyrethroids on the immune system based on the latest scientific research. The mechanism of action of pyrethroids include the delaying closure of voltage- sensitive sodium and chloride channels (including GABA- dependent channels). These compounds are neurotoxic. Studies have shown that they cause numerous immune disorders contributing to lowering of immunity in humans and animals. Exposure to pyrethroids can cause inhibition of proliferation of peripheral blood leukocytes and reducing the concentration of IgG immunolgobulines. They also cause reduced macrophages and decrease in interleukin 2 (IL-2), interleukin 8 (IL-8), interleukin 12p70 (IL-12p70), and interferon γ (IFN-γ). Some of these compounds cause increase of liver weight and increase of bone marrow cellularity, and may induce apoptosis of the thymus. Pyrethroids can cause allergies and asthma. Their immunosuppressive effects can impair host resistance against infections. Exposure to these compounds can also contribute to induction of the cancer, especially in patients with impaired immune function.

  20. Relationship between Early Inflammatory Response and Clinical Evolution of the Severe Multiorgan Failure in Mechanical Circulatory Support-Treated Patients

    Directory of Open Access Journals (Sweden)

    Raffaele Caruso

    2014-01-01

    Full Text Available Background. The mechanical circulatory support (MCS is an effective treatment in critically ill patients with end-stage heart failure (ESHF that, however, may cause a severe multiorgan failure syndrome (MOFS in these subjects. The impact of altered inflammatory response, associated to MOFS, on clinical evolution of MCS postimplantation patients has not been yet clarified. Methods. Circulating cytokines, adhesion molecules, and a marker of monocyte activation (neopterin were determined in 53 MCS-treated patients, at preimplant and until 2 weeks. MOFS was evaluated by total sequential organ failure assessment score (tSOFA. Results. During MCS treatment, 32 patients experienced moderate MOFS (tSOFA < 11; A group, while 21 patients experienced severe MOFS (tSOFA ≥ 11 with favorable (B group or adverse (n=13, C group outcomes. At preimplant, higher values of left ventricular ejection fraction (LVEF and estimated glomerular filtration rate (eGFR were the only parameter independently associated with A group. In C group, during the first postoperative week, high levels of interleukin-8 (IL-8 and tumor necrosis factor (TNF-α, and an increase of neopterin and adhesion molecules, precede tSOFA worsening and exitus. Conclusions. The MCS patients of C group show an excessive release to IL-8 and TNF-α, and monocyte-endothelial activation after surgery, that might contribute to the unfavourable evolution of severe MOFS.

  1. Association of markers of bacterial translocation with immune activation in decompensated cirrhosis

    DEFF Research Database (Denmark)

    Mortensen, Christian; Jensen, Jørgen Skov; Hobolth, Lise

    2014-01-01

    to be a promising surrogate marker for BT, although its clinical relevance has been questioned. MATERIALS AND METHODS: In 38 cirrhotic patients with and without SBP, bDNA in blood and ascites were assessed by 16S rDNA quantitative PCR. Levels of lipopolysaccharide-binding protein in plasma and highly sensitive C......-reactive protein, tumour necrosis factor-α, soluble urokinase plasminogen activating receptor, interleukin-6, interleukin 8, interferon-γ inducible protein-10 and vascular endothelial growth factor in plasma and ascites were measured by multiplex cytokine and ELISA assays. RESULTS: In patients without signs of SBP...... or positive cultures, we found a high frequency of bDNA but low concordance of bDNA between blood and ascites. Markers of inflammation were not significantly different between blood bDNA-positive (22%), ascites bDNA-positive (52%), and bDNA-negative patients. The 16S rDNA PCR failed to show bDNA in two out...

  2. A Novel Combination of Wheat Peptides and Fucoidan Attenuates Ethanol-Induced Gastric Mucosal Damage through Anti-Oxidant, Anti-Inflammatory, and Pro-Survival Mechanisms

    Directory of Open Access Journals (Sweden)

    Juntao Kan

    2017-09-01

    Full Text Available Gastritis or peptic ulcer is believed to affect about half of people worldwide. Traditional medications can lead to adverse effects, therefore, alternative nutritional strategies are needed to prevent the development of gastric mucosal damage. A novel combination of two food-grade ingredients, wheat peptides and fucoidan (WPF, was prepared to treat male Sprague Dawley rats for 30 days before gastric mucosal damage was induced by oral administration of ethanol. The serum levels of biomarkers were determined by enzyme-linked immunosorbent assay. Biomarkers in stomach tissue were analyzed using immunohistochemistry. In addition, human gastric epithelial cell line (GES-1 was used to investigate protein expression by Western blot. WPF could attenuate ethanol-induced gastric mucosal damage in an inverse dose-dependent manner, with both ulcer index and pathological index improved. WPF increased superoxide dismutase level and decreased malondialdehyde level. WPF also decreased the levels of interleukin-8, platelet-activating factor, and Caspase 3, while increasing the levels of prostaglandin E-2, epidermal growth factor (EGF, and EGF receptor (EGFR. Furthermore, phosphorylation of EGFR and extracellular signal–regulated kinases was induced by WPF in GES-1 cells. In conclusion, the novel combination of wheat peptides and fucoidan attenuated ethanol-induced gastric mucosal damage in rats through anti-oxidant, anti-inflammatory, and pro-survival mechanisms.

  3. n-Hexane Insoluble Fraction of Plantago lanceolata Exerts Anti-Inflammatory Activity in Mice by Inhibiting Cyclooxygenase-2 and Reducing Chemokines Levels.

    Science.gov (United States)

    Fakhrudin, Nanang; Dwi Astuti, Eny; Sulistyawati, Rini; Santosa, Djoko; Susandarini, Ratna; Nurrochmad, Arief; Wahyuono, Subagus

    2017-03-13

    Inflammation is involved in the progression of many disorders, such as tumors, arthritis, gastritis, and atherosclerosis. Thus, the development of new agents targeting inflammation is still challenging. Medicinal plants have been used traditionally to treat various diseases including inflammation. A previous study has indicated that dichloromethane extract of P. lanceolata leaves exerts anti-inflammatory activity in an in vitro model. Here, we examined the in vivo anti-inflammatory activities of a n -hexane insoluble fraction of P. lanceolata leaves dichloromethane extract (HIFPL). We first evaluated its potency to reduce paw edema induced by carrageenan, and the expression of the proinflammatory enzyme, cyclooxygenase (COX)-2, in mice. The efficacy of HIFPL to inhibit COX-2 was also evaluated in an in vitro enzymatic assay. We further studied the effect of HIFPL on leukocytes migration in mice induced by thioglycollate. The level of chemokines facilitating the migration of leukocytes was also measured. We found that HIFPL (40, 80, 160 mg/kg) demonstrated anti-inflammatory activities in mice. The HIFPL reduced the volume of paw edema and COX-2 expression. However, HIFPL acts as an unselective COX-2 inhibitor as it inhibited COX-1 with a slightly higher potency. Interestingly, HIFPL strongly inhibited leukocyte migration by reducing the level of chemokines, Interleukine-8 (IL-8) and Monocyte chemoattractant protein-1 (MCP-1).

  4. Long polar fimbriae participates in the induction of neutrophils transepithelial migration across intestinal cells infected with enterohemorrhagic E. coli O157:H7.

    Science.gov (United States)

    Vergara, Alejandra F; Vidal, Roberto M; Torres, Alfredo G; Farfan, Mauricio J

    2014-01-01

    Enterohemorrhagic Escherichia coli (EHEC) strains are causative agents of diarrhea and hemorrhagic colitis, both diseases associated with intestinal inflammation and cell damage. Several studies have correlated EHEC virulence factors to high levels of intestinal pro-inflammatory cytokines and we have previously described that the Long polar fimbriae (Lpf) is involved in the secretion of interleukin-8 (IL-8) and up-regulation of genes belonging to the NF-κB pathway using non-polarized epithelial intestinal T84 cells. In the current study, we evaluated the two EHEC O157 Lpf fimbriae (Lpf1 and Lpf2) for their ability to induce intestinal secretion of IL-8 and the activation of IL8, CCL20, and ICAM1 genes on polarized T84 cells. We also determined the participation of Lpf1 and Lpf2 in transepithelial migration of polymorphonuclear neutrophils (PMNs). Polarized T84 cells infected with EHEC revealed that both, Lpf1 and Lpf2, were required for the secretion of IL-8 and the induction of IL8, CCL20, and ICAM1 genes. Both fimbriae also played a role in the migration of PMNs trough the intestinal cells monolayer. Overall, the present work further demonstrated that the fimbriae Lpf1 and Lpf2 are important bacterial virulence factors that might be involved in the inflammatory responses associated with EHEC infections.

  5. Decrease in Dengue virus-2 infection and reduction of cytokine/chemokine production by Uncaria guianensis in human hepatocyte cell line Huh-7

    Directory of Open Access Journals (Sweden)

    Cíntia da Silva Mello

    Full Text Available ABSTRACT BACKGROUND Dengue fever may present hemorrhages and cavitary effusions as result of exacerbated immune responses. We investigated hydro-alcoholic extracts from leaves (UGL and bark (UGB of the medicinal species Uncaria guinanensis with respect to antiviral effects in Dengue virus (DENV infection and in immunological parameters associated with in vivo physiopathological features. METHODS Chemical profiles from UGB or UGL were compared in thin layer chromatography and 1H nuclear magnetic resonance using flavonoid compounds and a pentacyclic oxindole alkaloid-enriched fraction as references. DENV-2-infected hepatocytes (Huh-7 were treated with extracts. Cell viability, DENV antigens and immunological factors were detected by enzyme-linked immunosorbent assay (ELISA or flow cytometry. FINDINGS The UGL mainly differed from UGB by selectively containing the flavonoid kaempferitrin. UGB and UGL improved hepatocyte viability. Both extracts reduced intracellular viral antigen and inhibited the secretion of viral non-structural protein (NS1, which is indicative of viral replication. Reduction in secretion of macrophage migration inhibitory factor was achieved by UGB, of interleukin-6 by UGL, and of interleukin-8 by both UGB and UGL. MAIN CONCLUSIONS The U. guianensis extracts presented, antiviral and immunomodulatory effects for DENV and possibly a hepatocyte-protective activity. Further studies may be performed to consider these products as potential candidates for the development of an herbal product for the future treatment of dengue.

  6. Decrease in Dengue virus-2 infection and reduction of cytokine/chemokine production by Uncaria guianensis in human hepatocyte cell line Huh-7.

    Science.gov (United States)

    Mello, Cíntia da Silva; Valente, Ligia Maria Marino; Wolff, Thiago; Lima-Junior, Raimundo Sousa; Fialho, Luciana Gomes; Marinho, Cintia Ferreira; Azeredo, Elzinandes Leal; Oliveira-Pinto, Luzia Maria; Pereira, Rita de Cássia Alves; Siani, Antonio Carlos; Kubelka, Claire Fernandes

    2017-06-01

    Dengue fever may present hemorrhages and cavitary effusions as result of exacerbated immune responses. We investigated hydro-alcoholic extracts from leaves (UGL) and bark (UGB) of the medicinal species Uncaria guinanensis with respect to antiviral effects in Dengue virus (DENV) infection and in immunological parameters associated with in vivo physiopathological features. Chemical profiles from UGB or UGL were compared in thin layer chromatography and 1H nuclear magnetic resonance using flavonoid compounds and a pentacyclic oxindole alkaloid-enriched fraction as references. DENV-2-infected hepatocytes (Huh-7) were treated with extracts. Cell viability, DENV antigens and immunological factors were detected by enzyme-linked immunosorbent assay (ELISA) or flow cytometry. The UGL mainly differed from UGB by selectively containing the flavonoid kaempferitrin. UGB and UGL improved hepatocyte viability. Both extracts reduced intracellular viral antigen and inhibited the secretion of viral non-structural protein (NS1), which is indicative of viral replication. Reduction in secretion of macrophage migration inhibitory factor was achieved by UGB, of interleukin-6 by UGL, and of interleukin-8 by both UGB and UGL. MAIN. The U. guianensis extracts presented, antiviral and immunomodulatory effects for DENV and possibly a hepatocyte-protective activity. Further studies may be performed to consider these products as potential candidates for the development of an herbal product for the future treatment of dengue.

  7. ROS and NF-κB are involved in upregulation of IL-8 in A549 cells exposed to multi-walled carbon nanotubes

    International Nuclear Information System (INIS)

    Ye Shefang; Wu Yihui; Hou Zhenqing; Zhang Qiqing

    2009-01-01

    Carbon nanotubes (CNTs) have potential applications in biosensors, tissue engineering, and biomedical devices because of their unique physico-chemical, electronic and mechanical properties. However, there is limited literature data available concerning the biological properties and toxicity of CNTs. This study aimed to assess the toxicity exhibited by multi-walled CNTs (MWCNTs) and to elucidate possible molecular mechanisms underlying the biological effects of MWCNTs in A549 cells. Exposing A549 cells to MWCNTs led to cell death, changes in cell size and complexity, reactive oxygen species (ROS) production, interleukin-8 (IL-8) gene expression and nuclear factor (NF)-κB activation. Treatment of A549 cells with antioxidants prior to adding MWCNTs decreased ROS production and abrogated expression of IL-8 mRNA. Pretreatment of A549 cells with NF-κB inhibitors suppressed MWCNTs-induced IL-8 mRNA expression. These results indicate that MWCNTs are able to induce expression of IL-8 in A549 cells, at least in part, mediated by oxidative stress and NF-κB activation.

  8. Redox Stimulation of Human THP-1 Monocytes in Response to Cold Physical Plasma

    Directory of Open Access Journals (Sweden)

    Sander Bekeschus

    2016-01-01

    Full Text Available In plasma medicine, cold physical plasma delivers a delicate mixture of reactive components to cells and tissues. Recent studies suggested a beneficial role of cold plasma in wound healing. Yet, the biological processes related to the redox modulation via plasma are not fully understood. We here used the monocytic cell line THP-1 as a model to test their response to cold plasma in vitro. Intriguingly, short term plasma treatment stimulated cell growth. Longer exposure only modestly compromised cell viability but apparently supported the growth of cells that were enlarged in size and that showed enhanced metabolic activity. A significantly increased mitochondrial content in plasma treated cells supported this notion. On THP-1 cell proteome level, we identified an increase of protein translation with key regulatory proteins being involved in redox regulation (hypoxia inducible factor 2α, differentiation (retinoic acid signaling and interferon inducible factors, and cell growth (Yin Yang 1. Regulation of inflammation is a key element in many chronic diseases, and we found a significantly increased expression of the anti-inflammatory heme oxygenase 1 (HMOX1 and of the neutrophil attractant chemokine interleukin-8 (IL-8. Together, these results foster the view that cold physical plasma modulates the redox balance and inflammatory processes in wound related cells.

  9. Inhibition of chemokine expression in rat inflamed paws by systemic use of the antihyperalgesic oxidized ATP

    Directory of Open Access Journals (Sweden)

    Ticozzi Paolo

    2005-07-01

    Full Text Available Abstract Background We previously showed that local use of periodate oxidized ATP (oATP, a selective inhibitor of P2X7 receptors for ATP in rat paw treated with Freund's adjuvant induced a significant reduction of hyperalgesia Herein we investigate the role of oATP, in the rat paws inflamed by carrageenan, which mimics acute inflammation in humans. Results Local, oral or intravenous administration of a single dose of oATP significantly reduced thermal hyperalgesia in hind paws of rats for 24 hours, and such effect was greater than that induced by diclofenac or indomethacin. Following oATP treatment, the expression of the pro-inflammatory chemokines interferon-gamma-inducible protein-10 (IP-10, mon ocyte chemoattractant protein-1 (MCP-1 and interleukin-8 (IL-8 within the inflamed tissues markedly decreased on vessels and infiltrated cells. In parallel, the immunohistochemical findings showed an impairment, with respect to the untreated rats, in P2X7 expression, mainly on nerves and vessels close to the site of inflammation. Finally, oATP treatment significantly reduced the presence of infiltrating inflammatory macrophages in the paw tissue. Conclusion Taken together these results clearly show that oATP reduces carrageenan-induced inflammation in rats.

  10. Betalains increase vitexin-2-O-xyloside cytotoxicity in CaCo-2 cancer cells.

    Science.gov (United States)

    Farabegoli, F; Scarpa, E S; Frati, A; Serafini, G; Papi, A; Spisni, E; Antonini, E; Benedetti, S; Ninfali, P

    2017-03-01

    Vitexin-2-O-xyloside (XVX) from Beta vulgaris var. cicla L. (BVc) seeds, betaxanthin (R1) and betacyanin (R2) fractions from Beta vulgaris var. rubra L. (BVr) roots were combined and tested for cytotoxicity in CaCo-2 colon cancer cells. XVX was the most cytotoxic molecule, but the combination of XVX with R1 and R2 significantly prolonged its cytotoxicity. Cytotoxicity was mediated by the intrinsic apoptotic pathway, as shown by an increase in Bcl2-like protein 4, cleaved Poly ADP-Ribosyl Polymerase 1 and cleaved Caspase 3 levels with a parallel decrease in anti-apoptotic protein B-cell leukemia/lymphoma 2 levels. R1 and R2, used alone or in combination, reduced oxidative stress triggered by H 2 O 2 in CaCo-2 cells. Betalains dampened cyclooxygenase-2 and interleukin-8 mRNA expression after lipopolysaccharide induction in CaCo-2, showing an anti-inflammatory action. Our results support the use of a cocktail of R1, R2 and XVX as a chemopreventive tool against colon cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Fusobacterium nucleatum induces cytokine production through Toll-like-receptor-independent mechanism.

    Science.gov (United States)

    Quah, S Y; Bergenholtz, G; Tan, K S

    2014-06-01

    To determine whether Fusobacterium nucleatum's ability to invade cells allows the bacteria to activate pro-inflammatory response through cytosolic pattern recognition receptors, independent of surface Toll-like receptors (TLRs). HEK293T cells, which lack endogenous TLRs, and overexpressing dominant negative myeloid differentiation primary response gene 88 (MyD88DN) protein, were infected with F. nucleatum and the production of interleukin-8 (IL-8) was determined. The necessity for intracellular invasion of the bacteria for cytokine production was also investigated by blocking bacterial invasion with cytochalasin D. The roles of NFĸB and p38 mitogen-activated protein kinase (MAPK) and nucleotide-binding oligomerization domain-1 (NOD-1) signalling pathways in F. nucleatum-induced IL-8 secretion were determined. Fusobacterium nucleatum-infected HEK293T cells produced IL-8 independent of the MYD88 signalling. This response was inhibited by preventing F. nucleatum invasion into HEK293T cells. p38 MAPK but not the NFĸB signalling pathway was required for F. nucleatum-mediated IL-8 production. HEK293T cells expressed NOD-1 but not NOD-2. Yet, inhibition of NOD-1 signalling did not affect F. nucleatum-induced IL-8 secretion. Fusobacterium nucleatum invasion led to cytokine production, which is mediated by the p38 MAPK signalling but independent of TLRs, NOD-1, NOD-2 and NFĸB signalling. © 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  12. Coinfection with Fusobacterium nucleatum can enhance the attachment and invasion of Porphyromonas gingivalis or Aggregatibacter actinomycetemcomitans to human gingival epithelial cells.

    Science.gov (United States)

    Li, Yan; Guo, Hongmei; Wang, Xijun; Lu, Yang; Yang, Chunyu; Yang, Pishan

    2015-09-01

    This study was conducted to investigate effects of coinfection of Porphyromonas gingivalis (P. gingivalis) or Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) with Fusobacterium nucleatum (F. nucleatum) on their adhering and invasive capacity to human gingival epithelial cells as well as the expression of interleukin-8 (IL-8) and human beta-defensin-2 (hBD-2) in human gingival epithelial cells. P. gingivalis and A. actinomycetemcomitans were tested for their ability to attach and invade a human gingival epithelial cell line (Ca9-22) alone or coinfecting with F. nucleatum. Also, expression levels of IL-8 and hBD-2 were detected respectively using enzyme linked immunosorbent assay (ELISA) and real-time reverse transcription PCR (RT-PCR) when Ca9-22 cells were infected with P. gingivalis and A. actinomycetemcomitans alone or coinfecting with F. nucleatum. F. nucleatum, P. gingivalis and A. actinomycetemcomitans were allowed to adhere and invade Ca9-22 cells, either each strain alone or under coinfection. The adhering and invasive abilities of P. gingivalis and A. actinomycetemcomitans were significantly greater when they were coincubated with F. nucleatum (Pnucleatum. Also, galactose disrupted this inhibition on the expression of IL-8 and hBD-2. These results suggested coinfection with F. nucleatum can enhance adhesion and invasion of P. gingivalis and A. actinomycetemcomitans to Ca9-22 cells, as well as inhibition on host innate immune response. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Preventive Effects of Houttuynia cordata Extract for Oral Infectious Diseases

    Directory of Open Access Journals (Sweden)

    Yasuko Sekita

    2016-01-01

    Full Text Available Houttuynia cordata (HC (Saururaceae has been used internally and externally as a traditional medicine and as an herbal tea for healthcare in Japan. Our recent survey showed that HC poultice (HCP prepared from smothering fresh leaves of HC had been frequently used for the treatment of purulent skin diseases with high effectiveness. Our experimental study also demonstrated that ethanol extract of HCP (eHCP has antibacterial, antibiofilm, and anti-inflammatory effects against S. aureus which caused purulent skin diseases. In this study, we focused on novel effects of HCP against oral infectious diseases, such as periodontal disease and dental caries. We determined the antimicrobial and antibiofilm effects of water solution of HCP ethanol extract (wHCP against important oral pathogens and investigated its cytotoxicity and anti-inflammatory effects on human oral epithelial cells. wHCP had moderate antimicrobial effects against some oral microorganisms and profound antibiofilm effects against Fusobacterium nucleatum, Streptococcus mutans, and Candida albicans. In addition, wHCP had no cytotoxic effects and could inhibit interleukin-8 and CCL20 productions by Porphyromonas gingivalis lipopolysaccharide-stimulated human oral keratinocytes. Our findings suggested that wHCP may be clinically useful for preventing oral infectious diseases as a mouthwash for oral care.

  14. Acute and chronic effects of smoking on inflammation markers in exhaled breath condensate in current smokers.

    Science.gov (United States)

    Koczulla, A-Rembert; Noeske, Sarah; Herr, Christian; Jörres, Rudolf A; Römmelt, Horst; Vogelmeier, Claus; Bals, Robert

    2010-01-01

    Long-term cigarette smoking is associated with pulmonary inflammation, but the acute effects of smoking have been less well studied. Analysis of the exhaled breath condensate (EBC) can provide noninvasive markers that might be indicative of inflammation. The aim of the study was to determine whether the pH , electrical conductivity and the levels of ammonium and interleukin 8 (IL-8) of EBC were altered in smokers and whether they changed after smoking a single cigarette. We included 19 healthy nonsmokers (controls), 29 asymptomatic smokers, 10 patients with stable chronic obstructive pulmonary disease (COPD) [Global Initiative for Chronic Obstructive Lung Disease stages (GOLD) stages II-III], and 10 patients with exacerbated COPD. In 13 smokers, EBC was also analyzed before and after smoking. EBC was obtained during 10 min tidal breathing with a cooled RTube. pH was determined after deaeration with argon. Acute smoking did not alter the pH or ammonium and IL-8 levels, but raised conductivity. As in COPD patients, the pH was significantly decreased in chronic smokers with a history of at least 10 pack-years compared to controls. EBC can be used to detect the acute and chronic effects of smoking. The increased conductivity of EBC after smoking suggests acute inflammatory effects. The reduced pH in chronic smokers shows cigarette-induced inflammation. 2009 S. Karger AG, Basel.

  15. Lung Mucosa Lining Fluid Modification of Mycobacterium tuberculosis to Reprogram Human Neutrophil Killing Mechanisms.

    Science.gov (United States)

    Arcos, Jesús; Diangelo, Lauren E; Scordo, Julia M; Sasindran, Smitha J; Moliva, Juan I; Turner, Joanne; Torrelles, Jordi B

    2015-09-15

    We have shown that human alveolar lining fluid (ALF) contains homeostatic hydrolases capable of altering the Mycobacterium tuberculosis cell wall and subsequently its interaction with human macrophages. Neutrophils are also an integral part of the host immune response to M. tuberculosis infection. Here we show that the human lung mucosa influences M. tuberculosis interaction with neutrophils, enhancing the intracellular killing of ALF-exposed M. tuberculosis and up-regulating the expression of tumor necrosis factor and interleukin 8. In contrast, ALF-exposed M. tuberculosis does not induce neutrophil apoptosis or necrosis, degranulation, or release of extracellular traps, and it decreases the oxidative response. These results suggest an important role for the human alveolar mucosa: increasing the innate capacity of the neutrophil to recognize and kill M. tuberculosis by favoring the use of intracellular mechanisms, while at the same time limiting neutrophil extracellular inflammatory responses to minimize their associated tissue damage. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Cigarette smoke inhibits airway epithelial cell innate immune responses to bacteria.

    Science.gov (United States)

    Kulkarni, Ritwij; Rampersaud, Ryan; Aguilar, Jorge L; Randis, Tara M; Kreindler, James L; Ratner, Adam J

    2010-05-01

    The human upper respiratory tract, including the nasopharynx, is colonized by a diverse array of microorganisms. While the host generally exists in harmony with the commensal microflora, under certain conditions, these organisms may cause local or systemic disease. Respiratory epithelial cells act as local sentinels of the innate immune system, responding to conserved microbial patterns through activation of signal transduction pathways and cytokine production. In addition to colonizing microbes, these cells may also be influenced by environmental agents, including cigarette smoke (CS). Because of the strong relationship among secondhand smoke exposure, bacterial infection, and sinusitis, we hypothesized that components in CS might alter epithelial cell innate immune responses to pathogenic bacteria. We examined the effect of CS condensate (CSC) or extract (CSE) on signal transduction and cytokine production in primary and immortalized epithelial cells of human or murine origin in response to nontypeable Haemophilus influenzae and Staphylococcus aureus. We observed that epithelial production of interleukin-8 (IL-8) and IL-6 in response to bacterial stimulation was significantly inhibited in the presence of CS (P 0.05 compared to cells without CSC treatment). These results identify a novel oxidant-mediated immunosuppressive role for CS in epithelial cells.

  17. Irradiation enhances the tumor tropism and therapeutic potential of tumor necrosis factor-related apoptosis-inducing ligand-secreting human umbilical cord blood-derived mesenchymal stem cells in glioma therapy.

    Science.gov (United States)

    Kim, Seong Muk; Oh, Ji Hyeon; Park, Soon A; Ryu, Chung Heon; Lim, Jung Yeon; Kim, Dal-Soo; Chang, Jong Wook; Oh, Wonil; Jeun, Sin-Soo

    2010-12-01

    Irradiation is a standard therapy for gliomas and many other cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising candidates for cancer gene therapy. Here, we show that tumor irradiation enhances the tumor tropism of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) and the therapeutic effect of TRAIL delivered by UCB-MSCs. The sequential treatment with irradiation followed by TRAIL-secreting UCB-MSCs (MSC-TRAIL) synergistically enhanced apoptosis in either TRAIL-sensitive or TRAIL-resistant glioma cells by upregulating the death receptor 5 and by inducing caspase activation. Migration assays showed greater MSC migration toward irradiated glioma cells and the tumor site in glioma-bearing mice compared with unirradiated tumors. Irradiated glioma cells had increased expression of interleukin-8 (IL-8), which leads to the upregulation of the IL-8 receptor on MSCs. This upregulation, which is involved in the migratory capacity of UCB-MSCs, was confirmed by siRNA inhibition and an antibody-neutralizing assay. In vivo survival experiments in orthotopic xenografted mice showed that MSC-based TRAIL gene delivery to irradiated tumors had greater therapeutic efficacy than a single treatment. These results suggest that clinically relevant tumor irradiation increases the therapeutic efficacy of MSC-TRAIL by increasing tropism of MSCs and TRAIL-induced apoptosis, which may be a more useful strategy for cancer gene therapy.

  18. Controlled exposure to diesel exhaust and traffic noise--Effects on oxidative stress and activation in mononuclear blood cells.

    Science.gov (United States)

    Hemmingsen, Jette Gjerke; Møller, Peter; Jantzen, Kim; Jönsson, Bo A G; Albin, Maria; Wierzbicka, Aneta; Gudmundsson, Anders; Loft, Steffen; Rissler, Jenny

    2015-05-01

    Particulate air pollution increases risk of cancer and cardiopulmonary disease, partly through oxidative stress. Traffic-related noise increases risk of cardiovascular disease and may cause oxidative stress. In this controlled random sequence study, 18 healthy subjects were exposed for 3h to diesel exhaust (DE) at 276 μg/m(3) from a passenger car or filtered air, with co-exposure to traffic noise at 48 or 75 dB(A). Gene expression markers of inflammation, (interleukin-8 and tumor necrosis factor), oxidative stress (heme oxygenase (decycling-1)) and DNA repair (8-oxoguanine DNA glycosylase (OGG1)) were unaltered in peripheral blood mononuclear cells (PBMCs). No significant differences in DNA damage levels, measured by the comet assay, were observed after DE exposure, whereas exposure to high noise levels was associated with significantly increased levels of hOGG1-sensitive sites in PBMCs. Urinary levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine were unaltered. In auxiliary ex vivo experiments whole blood was incubated with particles from the exposure chamber for 3h without effects on DNA damage in PBMCs or intracellular reactive oxygen species production and expression of CD11b and CD62L adhesion molecules in leukocyte subtypes. 3-h exposure to DE caused no genotoxicity, oxidative stress or inflammation in PBMCs, whereas exposure to noise might cause oxidatively damaged DNA. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Pro- and anti-inflammatory cytokines in post-infarction left ventricular remodeling.

    Science.gov (United States)

    Zarrouk-Mahjoub, S; Zaghdoudi, M; Amira, Z; Chebi, H; Khabouchi, N; Finsterer, J; Mechmeche, R; Ghazouani, E

    2016-10-15

    Acute myocardial infarction (MI) leads to molecular, structural, geometric and functional changes in the heart during a process known as ventricular remodeling. Myocardial infarction is followed by an inflammatory response in which pro- and anti-inflammatory cytokines play a crucial role, particularly in left ventricular remodeling. This study aimed at evaluating serum concentrations of interleukin-8 (IL8), tumor-necrosis-factor-alpha (TNFα) and interleukin-10 (IL10), pro- and anti-inflammatory cytokines, and at correlating them with left ventricular remodeling as assessed by echocardiographic parameters. In a case-control study 30 MI patients were compared with 30 healthy controls. Serum concentrations of IL8, TNFα and IL10 were measured on day 2 and day 30 post-MI by chemiluminescence immunoassay and correlated with echocardiographic parameters. There was an increase of IL8, and TNFα together with a decrease of IL10 at both time points. IL8 was negatively correlated with the left ventricular end-diastolic diameter (LVEDD) and positively with left ventricular systolic volume. IL10 was negatively correlated with LVEDD and left atrial volume 30days post-MI. The increase of pro-inflammatory cytokines TNFα and IL8 was accompanied by decreased anti-inflammatory IL10. This imbalance between pro- and anti-inflammatory cytokines might contribute to the progression of left ventricular remodeling and may lead to heart failure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Effects of linezolid on suppressing in vivo production of staphylococcal toxins and improving survival outcomes in a rabbit model of methicillin-resistant Staphylococcus aureus necrotizing pneumonia.

    Science.gov (United States)

    Diep, Binh An; Afasizheva, Anna; Le, Hoan N; Kajikawa, Osamu; Matute-Bello, Gustavo; Tkaczyk, Christine; Sellman, Bret; Badiou, Cedric; Lina, Gerard; Chambers, Henry F

    2013-07-01

     Linezolid is recommended for treatment of pneumonia and other invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The premise underlying this recommendation is that linezolid inhibits in vivo production of potent staphylococcal exotoxins, including Panton-Valentine leukocidin (PVL) and α-hemolysin (Hla), although supporting evidence is lacking.  A rabbit model of necrotizing pneumonia using MRSA clone USA300 was used to compare therapeutic effects of linezolid (50 mg/kg 3 times/day) and vancomycin (30 mg/kg 2 times/day) administered 1.5, 4, and 9 hours after infection on host survival outcomes and in vivo bacterial toxin production.  Mortality rates were 100% for untreated rabbits and 83%-100% for vancomycin-treated rabbits. In contrast, mortality rates were 25%, 50%, and 100% for rabbits treated with linezolid 1.5, 4, and 9 hours after infection, respectively. Compared with untreated and vancomycin-treated rabbits, improved survival of rabbits treated 1.5 hours after infection with linezolid was associated with a significant decrease in bacterial counts, suppressed bacterial production of PVL and Hla, and reduced production of the neutrophil-chemoattractant interleukin 8 in the lungs.  Across the study interval, only early treatment with linezolid resulted in significant suppression of exotoxin synthesis and improved survival outcomes in a rabbit model of MRSA necrotizing pneumonia.

  1. Proteomic Analysis of Lung Tissue in a Rat Acute Lung Injury Model: Identification of PRDX1 as a Promoter of Inflammation

    Directory of Open Access Journals (Sweden)

    Dongdong Liu

    2014-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes of Pseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS challenge in airway epithelial cells in vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6, interleukin-8 (IL-8, and tumor necrosis factor-α (TNF-α, whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI.

  2. The influence of platelet membranes on tumour cell behaviour.

    Science.gov (United States)

    Coupland, L A; Hindmarsh, E J; Gardiner, E E; Parish, C R

    2017-06-01

    The significant role of platelets in the protection of tumour cells from immune attack and shear forces and the promotion of tumour cell extravasation from the bloodstream in the process of haematogenous metastasis have been extensively studied. The role of platelets, and in particular platelet membranes, in the promotion of a more metastatic phenotype in tumour cells is a more recent and, therefore, less well-recognised area of research. This review article summarises studies that have focused on the impact of tumour cell interactions with platelets and platelet membranes on tumour cell behaviour in vitro and in vivo. Furthermore, the gene expression changes that occur within tumour cells following contact with platelet membranes are also extensively reviewed. Overall, the interaction of platelet membranes with tumour cells results in a more invasive phenotype and the promotion of epithelial to mesenchymal transition with our own genetic studies revealing that matrix metalloproteinase-1, plasminogen activator inhibitor-1 and interleukin-8 are globally upregulated in a range of tumour cell lines.

  3. Total flavonoid extract from Coreopsis tinctoria Nutt. protects rats against myocardial ischemia/reperfusion injury.

    Science.gov (United States)

    Zhang, Ya; Yuan, Changsheng; Fang, He; Li, Jia; Su, Shanshan; Chen, Wen

    2016-09-01

    This study aimed to evaluate the protective effects of total flavonoid extract from Coreopsis tinctoria Nutt. (CTF) against myocardial ischemia/reperfusion injury (MIRI) using an isolated Langendorff rat heart model. Left ventricular developed pressure (LVDP) and the maximum rate of rise and fall of LV pressure (±dp/dtmax) were recorded. Cardiac injury was assessed by analyzing lactate dehydrogenase (LDH) and creatine kinase (CK) released in the coronary effluent. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels were determined. Myocardial inflammation was assessed by monitoring tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), and interleukin-6 (IL-6) levels. Myocardial infarct size was estimated. Cell morphology was assessed by 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin (HE) staining. Cardiomyocyte apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Pretreatment with CTF significantly increased the heart rate and increased LVDP, as well as SOD and GSH-Px levels. In addition, CTF pretreatment decreased the TUNEL-positive cell ratio, infarct size, and levels of CK, LDH, MDA, TNF-α, CRP, IL-6, and IL-8. These results suggest that CTF exerts cardio-protective effects against MIRI via anti-oxidant, anti-inflammatory, and anti-apoptotic activities.

  4. Early hematological and immunological alterations in gasoline station attendants exposed to benzene.

    Science.gov (United States)

    Moro, Angela M; Brucker, Natália; Charão, Mariele F; Sauer, Elisa; Freitas, Fernando; Durgante, Juliano; Bubols, Guilherme; Campanharo, Sarah; Linden, Rafael; Souza, Ana P; Bonorino, Cristina; Moresco, Rafael; Pilger, Diogo; Gioda, Adriana; Farsky, Sandra; Duschl, Albert; Garcia, Solange C

    2015-02-01

    Elucidation of effective biomarkers may provide tools for the early detection of biological alterations caused by benzene exposure and may contribute to the reduction of occupational diseases. This study aimed to assess early alterations on hematological and immunological systems of workers exposed to benzene. Sixty gasoline station attendants (GSA group) and 28 control subjects were evaluated. Environmental and biological monitoring of benzene exposure was performed in blood and urine. The potential effect biomarkers evaluated were δ-aminolevulinate dehydratase (ALA-D) activity, CD80 and CD86 expression in lymphocytes and monocytes, and serum interleukin-8 (IL-8). The influence of confounding factors and toluene co-exposure were considered. Although exposures were below ACGIH (American Conference of Governmental Industrial Hygienists) limits, reduced ALA-D activity, decreased CD80 and CD86 expression in monocytes and increased IL-8 levels were found in the GSA group compared to the control subjects. Furthermore, according to multiple linear regression analysis, benzene exposure was associated to a decrease in CD80 and CD86 expression in monocytes. These findings suggest, for the first time, a potential effect of benzene exposure on ALA-D activity, CD80 and CD86 expression, IL-8 levels, which could be suggested as potential markers for the early detection of benzene-induced alterations. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Biodiesel from Soybean Promotes Cell Proliferation in Vitro

    Science.gov (United States)

    Gioda, Adriana; Rodríguez-Cotto, Rosa I.; Amaral, Beatriz Silva; Encarnación-Medina, Jarline; Ortiz-Martínez, Mario G.; Jiménez-Vélez, Braulio D.

    2016-01-01

    Toxicological responses of exhaust emissions of biodiesel are different due to variation in methods of generation and the tested biological models. A chemical profile was generated using ICP-MS and GC-MS for the biodiesel samples obtained in Brazil. A cytotoxicity assay and cytokine secretion experiments were evaluated in human bronchial epithelial cells (BEAS-2B). Cells were exposed to polar (acetone) and nonpolar (hexane) extracts from particles obtained from fuel exhaust: fossil diesel (B5), pure soybean biodiesel (B100), soybean biodiesel with additive (B100A) and ethanol additive (EtOH). Biodiesel and its additives exhibited higher organic and inorganic constituents on particles when compared to B5. The biodiesel extracts did not exert any toxic effect at concentrations 10, 25, 50, 75, and 100 μg mL -1. In fact quite the opposite, a cell proliferation effect induced by the B100 and B100A extracts is reported. A small increase in concentrations of inflammatory mediators (Interleukin-6, IL-6; and Interleukin-8, IL-8) in the medium of biodiesel-treated cells was observed, however, no statistical difference was found. An interesting finding indicates that the presence of metals in the nonpolar (hexane) fraction of biodiesel fuel (B100) represses cytokine release in lung cells. This was revealed by the use of the metal chelator. Results suggest that metals associated with biodiesel’s organic constituents might play a significant role in molecular mechanisms associated to cellular proliferation and immune responses. PMID:27179667

  6. Toxic effects of brake wear particles on epithelial lung cells in vitro

    Directory of Open Access Journals (Sweden)

    Perrenoud Alain

    2009-11-01

    Full Text Available Abstract Background Fine particulate matter originating from traffic correlates with increased morbidity and mortality. An important source of traffic particles is brake wear of cars which contributes up to 20% of the total traffic emissions. The aim of this study was to evaluate potential toxicological effects of human epithelial lung cells exposed to freshly generated brake wear particles. Results An exposure box was mounted around a car's braking system. Lung cells cultured at the air-liquid interface were then exposed to particles emitted from two typical braking behaviours („full stop“ and „normal deceleration“. The particle size distribution as well as the brake emission components like metals and carbons was measured on-line, and the particles deposited on grids for transmission electron microscopy were counted. The tight junction arrangement was observed by laser scanning microscopy. Cellular responses were assessed by measurement of lactate dehydrogenase (cytotoxicity, by investigating the production of reactive oxidative species and the release of the pro-inflammatory mediator interleukin-8. The tight junction protein occludin density decreased significantly (p Conclusion These findings suggest that the metals on brake wear particles damage tight junctions with a mechanism involving oxidative stress. Brake wear particles also increase pro-inflammatory responses. However, this might be due to another mechanism than via oxidative stress.

  7. Soluble CD163 and soluble mannose receptor predict survival and decompensation in patients with liver cirrhosis, and correlate with gut permeability and bacterial translocation

    DEFF Research Database (Denmark)

    Rainer, F; Horvath, A; Sandahl, T D

    2017-01-01

    BACKGROUND: Activated hepatic macrophages play a key role in inflammation and fibrosis progression in chronic liver disease. AIM: To assess the prognostic value of soluble (s)CD163 and mannose receptor (sMR) in cirrhotic patients and explore associations with markers of intestinal permeability...... (lactulose-mannitol ratio, diamine oxidase), bacterial translocation (endotoxin, lipopolysaccharide-binding protein) and markers of systemic immune activation (interleukin-6, interleukin-8, sCD14). METHODS: We prospectively investigated 101 cirrhotic patients (Child-Pugh class A: n = 72, Child-Pugh classes B.......3, Child-Pugh class A = 4.2, Child-Pugh classes B and C = 8.4 mg/L; sMR in healthy controls = 15.8, Child-Pugh class A = 36.5, Child-Pugh classes B and C = 66.3 μg/dL). A total of 21 patients died during the observation period. Patients with sCD163 levels above 5.9 mg/L showed significantly reduced...

  8. Novel sulfated polysaccharides disrupt cathelicidins, inhibit RAGE and reduce cutaneous inflammation in a mouse model of rosacea.

    Directory of Open Access Journals (Sweden)

    Jianxing Zhang

    2011-02-01

    Full Text Available Rosacea is a common disfiguring skin disease of primarily Caucasians characterized by central erythema of the face, with telangiectatic blood vessels, papules and pustules, and can produce skin thickening, especially on the nose of men, creating rhinophyma. Rosacea can also produce dry, itchy eyes with irritation of the lids, keratitis and corneal scarring. The cause of rosacea has been proposed as over-production of the cationic cathelicidin peptide LL-37.We tested a new class of non-anticoagulant sulfated anionic polysaccharides, semi-synthetic glycosaminoglycan ethers (SAGEs on key elements of the pathogenic pathway leading to rosacea. SAGEs were anti-inflammatory at ng/ml, including inhibition of polymorphonuclear leukocyte (PMN proteases, P-selectin, and interaction of the receptor for advanced glycation end-products (RAGE with four representative ligands. SAGEs bound LL-37 and inhibited interleukin-8 production induced by LL-37 in cultured human keratinocytes. When mixed with LL-37 before injection, SAGEs prevented the erythema and PMN infiltration produced by direct intradermal injection of LL-37 into mouse skin. Topical application of a 1% (w/w SAGE emollient to overlying injected skin also reduced erythema and PMN infiltration from intradermal LL-37.Anionic polysaccharides, exemplified by SAGEs, offer potential as novel mechanism-based therapies for rosacea and by extension other LL-37-mediated and RAGE-ligand driven skin diseases.

  9. Airway function and markers of airway inflammation in patients with treated hypothyroidism.

    Science.gov (United States)

    Birring, S S; Patel, R B; Parker, D; McKenna, S; Hargadon, B; Monteiro, W R; Falconer Smith, J F; Pavord, I D

    2005-03-01

    There is increasing evidence of an association between organ specific autoimmune diseases, particularly autoimmune thyroid disease and respiratory morbidity. A study was undertaken to determine whether patients with autoimmune thyroid disease have objective evidence of airway inflammation and dysfunction. Twenty six non-smoking women with treated hypothyroidism and 19 non-smoking controls completed a symptom questionnaire and underwent full lung function tests, capsaicin cough reflex sensitivity measurement, methacholine challenge test, and sputum induction over two visits. Symptoms of cough (p = 0.01), dyspnoea (p = 0.01), sputum production (p = 0.004), and wheeze (p = 0.04) were reported more commonly in patients than controls. Patients with hypothyroidism had heightened cough reflex sensitivity compared with controls (geometric mean concentration of capsaicin causing five coughs: 40 v 108 mmol/l; mean difference 1.4 doubling doses; 95% confidence interval of difference 0.4 to 2.5; p = 0.008) and a significantly higher proportion of patients had airway hyperresponsiveness (methacholine provocative concentration (PC(20)) <8 mg/ml: 38% v 0%; p = 0.016). Patients with hypothyroidism also had a significantly higher induced sputum total neutrophil cell count (p = 0.01), total lymphocyte count (p = 0.02), and sputum supernatant interleukin-8 concentrations (p = 0.048). Patients with treated hypothyroidism report more respiratory symptoms and have objective evidence of airway dysfunction and inflammation.

  10. Thermal injury, the inflammatory process, and wound dressing reduce human neutrophil chemotaxis to four attractants.

    Science.gov (United States)

    Hasslen, S R; Nelson, R D; Ahrenholz, D H; Solem, L D

    1993-01-01

    The purpose of this study was to assess the influence of thermal injury and the inflammatory process on chemotactic responses of neutrophils to four attractants (N-formyl-methionyl-leucyl-phenylalanine, the complement fragment C5a, interleukin-8, and leukotriene B4) under agarose, expression of Mac-1 (CD11b/CD18) adherence receptors on the cell surface, and polymerization of actin in the cell cytoplasm. Circulating neutrophils were isolated from peripheral blood, and exudate neutrophils from fluid collecting under two different wound dressings applied to abrasion sites of healthy subjects and to skin graft donor sites of patients with burns. Burn injury reduced the chemotactic responses of circulating neutrophils to all four attractants, suggesting a "global" defect in chemotactic function. Patient-exudate neutrophils collected under Tegaderm exhibited further decrements in all chemotactic responses, and patient-exudate neutrophils collected under Biobrane were nonmotile. The exudate neutrophils collected under Biobrane expressed high levels of Mac-1 receptors and irreversibly polymerized actin, which may contribute to the nonmotility of these exudate cells.

  11. TLR4-dependent recognition of lipopolysaccharide by epithelial cells requires sCD14.

    Science.gov (United States)

    Bäckhed, Fredrik; Meijer, Lisa; Normark, Staffan; Richter-Dahlfors, Agneta

    2002-08-01

    Epithelial cells lining the urinary bladder mucosa are engaged in numerous functions that act in concert to prevent exposure of the sensitive upper urinary tract to bacteria. This protective effect was recently suggested to be achieved mainly by compartmentalized, organ-specific expression of the lipopolysaccharide (LPS) receptor Toll-like receptor (TLR) 4 within epithelial cells of the urogenital tract. Here, we show that bladder epithelial cells recognize similarly low amounts of LPS as macrophages. LPS responsiveness measured as secretion of the chemoattractant interleukin 8 demonstrates a dependency on TLR4 in epithelial cells, which is similar to the situation in macrophages. The TLR4-mediated LPS response in bladder epithelial cells also uses the co-receptor CD14 for efficient LPS signalling. However, bladder epithelial cells do not express endogenous CD14 and are therefore dependent on the soluble form of CD14 that is present in body fluids. Furthermore, we demonstrate that epithelial chemokine production is augmented by type 1-mediated attachment of uropathogenic Escherichia coli in the absence, but not in the presence, of CD14. Collectively, our findings strengthen the role for bladder epithelial cells as important players in the innate immune system within the urinary tract.

  12. Sarcoptes scabiei (Acari: Sarcoptidae) mite extract modulates expression of cytokines and adhesion molecules by human dermal microvascular endothelial cells.

    Science.gov (United States)

    Elder, B Laurel; Arlian, Larry G; Morgan, Marjorie S

    2006-09-01

    The inflammatory and immune responses seen with the worldwide disease scabies, caused by the mite Sarcoptes scabiei (De Geer) (Acari: Sarcoptidae), are complex. Clinical symptoms are delayed for weeks in patients when they are infested with scabies for the first time. This study was undertaken to elucidate the role of the human dermal microvascular endothelial cell (HMVEC-D) in modulating the inflammatory and immune responses in the skin to S. scabiei. Extracts of S. scabiei were incubated with HMVEC-D and the expression of adhesion molecules and chemokine receptors on the cells and the secretion of selected cytokines were determined by enzyme-linked immunosorbent assay. S. scabiei extract was found to inhibit HMVEC-D expression of E-selectin and vascular cell adhesion molecule-1, although not intercellular adhesion molecule-1. The secretion of interleukin-8 also was inhibited by S. scabiei extract. S. scabiei extract increased expression of the chemokine receptor CXCR-1 and both down-regulated and up-regulated expression of CXCR-2, depending on the concentration tested. These findings help explain the delayed inflammatory reaction to infestation with S. scabiei.

  13. The effect of metformin on monocyte secretory function in simvastatin-treated patients with impaired fasting glucose.

    Science.gov (United States)

    Krysiak, Robert; Okopien, Bogusław

    2013-01-01

    This study was designed to investigate whether metformin affects monocyte secretory function in patients with impaired fasting glucose receiving chronic statin therapy. The study included 48 patients with impaired fasting glucose treated for at least three months with simvastatin (40 mg daily). These patients were randomized to either metformin (3 g daily) or placebo, which was administered together with simvastatin for 90 days. Plasma lipids, glucose homeostasis markers, monocyte cytokine release and plasma C-reactive protein levels were determined before randomization and at the end of the treatment. Compared to placebo, metformin reduced monocyte release of tumor necrosis factor-α, interleukin-1β, interleukin-6, monocyte chemoattractant protein-1 and interleukin-8, as well as decreased plasma C-reactive protein levels, which were accompanied by an improvement in insulin sensitivity. The obtained results suggest that metformin may inhibit monocyte secretory function and reduce systemic inflammation in statin-treated patients with prediabetes. Impaired fasting glucose patients with high cardiovascular risk may receive the greatest benefits from concomitant treatment with a statin and metformin. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Effects of combined therapy of traditional Chinese medicine and western medicine on platelets, coagulative functions and inflammatory cytokines with ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Yun-Xia Lei

    2016-07-01

    Full Text Available Objective: To explore the effects of combined therapy of traditional Chinese medicine and western medicine on platelets, coagulative functions and inflammatory cytokines in patients with ulcerative colitis (UC. Methods: A total of 267 patients with UC were collected. 137 patients were treated with combined therapy of traditional Chinese medicine and western medicine as experimental group and 130 patients were treated with only western medicine as controls. Platelet count, coagulation function indexes and inflammatory cytokines were measured before and 15 d after the treatment. Results: No significantly differences were found in all indexes before treatment between two groups. After different treatments, platelet count (PLT, platelet distribution width (PDW were significantly decreased in both groups, but mean platelet volumn (MPV were significantly increased than before treatment. PLT and PDW were significantly lower and MPV were significantly higher in experimental group than control group. Fibrinogen (Fib and D-dimer (DD decreased significantly after treatment. Fib and DD in experimental group were significantly lower than controls. No significantly differences were found in activated partial thromboplastin time (APTT and prothrobin time (PT. Tumor necrosisi factor-α (TNF-α, interleukin-6 (IL-6 and interleukin-8 (IL-8 decreased significantly in both group after treatment. TNF-毩, IL-6 and IL-8 were significantly lower in experimental group than controls. Conclusion: Combined therapy of traditional Chinese medicine and western medicine can more effectively improve the cogulation, fibrinolysis and inflammation in patients with UC than only western medicine therapy.

  15. Immune response of chicken gut to natural colonization by gut microflora and to Salmonella enterica serovar enteritidis infection.

    Science.gov (United States)

    Crhanova, Magdalena; Hradecka, Helena; Faldynova, Marcela; Matulova, Marta; Havlickova, Hana; Sisak, Frantisek; Rychlik, Ivan

    2011-07-01

    In commercial poultry production, there is a lack of natural flora providers since chickens are hatched in the clean environment of a hatchery. Events occurring soon after hatching are therefore of particular importance, and that is why we were interested in the development of the gut microbial community, the immune response to natural microbial colonization, and the response to Salmonella enterica serovar Enteritidis infection as a function of chicken age. The complexity of chicken gut microbiota gradually increased from day 1 to day 19 of life and consisted of Proteobacteria and Firmicutes. For the first 3 days of life, chicken cecum was protected by increased expression of chicken β-defensins (i.e., gallinacins 1, 2, 4, and 6), expression of which dropped from day 4 of life. On the other hand, a transient increase in interleukin-8 (IL-8) and IL-17 expression could be observed in chicken cecum on day 4 of life, indicating physiological inflammation and maturation of the gut immune system. In agreement, the response of chickens infected with S. Enteritidis on days 1, 4, and 16 of life shifted from Th1 (characterized mainly by induction of gamma interferon [IFN-γ] and inducible nitric oxide synthase [iNOS]), observed in younger chickens, to Th17, observed in 16-day-old chickens (characterized mainly by IL-17 induction). Active modification of chicken gut microbiota in the future may accelerate or potentiate the maturation of the gut immune system and increase its resistance to infection with different pathogens.

  16. Differential modulation of resistance biomarkers in skin of juvenile and mature pink salmon, Oncorhynchus gorbuscha by the salmon louse, Lepeophtheirus salmonis.

    Science.gov (United States)

    Braden, Laura M; Barker, Duane E; Koop, Ben F; Jones, Simon R M

    2015-11-01

    Juvenile pink salmon larger than 0.7 g reject the sea louse, Lepeophtheirus salmonis, and are considered resistant to the infection. Robust innate defense responses in the skin contribute to the observed resistance. In contrast adult pink salmon captured at sea or shortly before spawning carry large numbers of the parasite, suggesting inability to control the infection. The purpose of this research is to better understand these apparently contradictory conclusions by comparing a suite of genetic and cellular markers of resistance to L. salmonis in the skin of juvenile and mature pink salmon. The expression of major histocompatibility factor II, C-reactive protein, interleukin-1β, interleukin-8 and cyclooxygenase-2 was down-regulated in mature but not juvenile pink salmon. Similarly, skin at the site of parasite attachment in juvenile salmon was highly populated with MHIIβ(+) and IL-1β(+) cells that were either absent, or at reduced levels at similar sites in mature salmon. In addition, mucocyte density was relatively low in the skin of mature salmon, irrespective of louse infection. In juveniles, the higher mucocyte density decreased following louse attachment. We show that in mature pink salmon, genetic and histological responses in skin are depressed and speculate that salmonid defense against L. salmonis is modulated by maturation. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  17. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort.

    Science.gov (United States)

    Han, MeiLan K; Quibrera, Pedro M; Carretta, Elizabeth E; Barr, R Graham; Bleecker, Eugene R; Bowler, Russell P; Cooper, Christopher B; Comellas, Alejandro; Couper, David J; Curtis, Jeffrey L; Criner, Gerard; Dransfield, Mark T; Hansel, Nadia N; Hoffman, Eric A; Kanner, Richard E; Krishnan, Jerry A; Martinez, Carlos H; Pirozzi, Cheryl B; O'Neal, Wanda K; Rennard, Stephen; Tashkin, Donald P; Wedzicha, Jadwiga A; Woodruff, Prescott; Paine, Robert; Martinez, Fernando J

    2017-08-01

    567 (51%) had none. 82 (7%) of 1105 patients had at least one acute exacerbation each year, whereas only 23 (2%) had two or more acute exacerbations in each year. An inconsistent pattern (both years with and without acute exacerbations) was common (456 [41%] of the group), particularly among GOLD stages 3 and 4 patients (256 [56%] of 456). In logistic regression, consistent acute exacerbations (≥1 event per year for 3 years) were associated with higher baseline symptom burden, previous exacerbations, greater evidence of small airway abnormality on CT, lower interleukin-15 concentrations, and higher interleukin-8 concentrations, than were no acute exacerbations. Although acute exacerbations are common, the exacerbation status of most individuals varies markedly from year to year. Among patients who had any acute exacerbation over 3 years, very few repeatedly had two or more events per year. In addition to symptoms and history of exacerbations in the year before study enrolment, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, and interleukin-15 and interleukin-8 concentrations. National Institutes of Health, and National Heart, Lung, and Blood Institute. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Korelasi Jumlah Streptococcus mutans (S. mutans dan Level Ekspresi Interlukin 8 (IL-8 pada Severe Early Childhood Caries

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    Muhammad Luthfi

    2015-12-01

    Full Text Available Karies gigi pada anak usia dini merupakan masalah kesehatan yang sangat serius karena merupakan penyakit infeksi kronis yang menular. Dalam beberapa tahun terakhir pandangan tentang neutrofil telah berubah secara dramatis. Neutrofil tidak hanya berperan sebagai pembunuh mikroba melalui proses fagositosis, pelepasan reactive oxigen species (ROS dan peptida antimikrobialnya tetapi neutrofil turut mengatur aktifasi respon imun. Interleukin-8 (IL-8 berfungsi sebagai aktivator kuat dan kemoatraktan neutrofil oleh karena itu IL-8 merupakan mediator kunci dalam migrasi neutrofil ke lokasi peradangan dan infeksi. Untuk menganalisis hubungan dari jumlah S. mutans dan ekspresi IL-8 neutrofil saliva pada anak usia dini bebas karies dan severe early childhood caries (S-ECC. Perlakuan dilakukan pada dua kelompok yaitu isolasi dan menghitung jumlah S. mutans pada sampel saliva dan sampel hasil kumur dengan NaCl 1,5% yang diisolasi neutrofilnya kemudian dianalisis ekspresi IL-8 menggunakan flow cytometry dari 20 anak bebas karies dan 20 anak severe early childhood caries. Hasil nilai rata-rata diketahui bahwa jumlah S. mutans anak usia dini bebas karies lebih rendah (513.500,00±185.565,28 CFU/ml dibandingkan dengan S-ECC (977.000,00±222.500,15 CFU/ml, sedangkan ekspresi IL-8 neutrofil saliva anak usia dini bebas karies lebih tinggi (3,31±0,50 dibandingkan dengan S-ECC (2,95+0,56. Penurunan ekspresi IL-8 neutrofil saliva kemungkinan sebagai penyebab meningkatnya jumlah S. mutans pada S-ECC. Correlation of Streptococcus mutans (S. mutans Level and Interleukin 8 (IL-8 Expressions of Salivary Neutrophils in Severe Early Childhood Caries. Early childhood caries is a very serious health problem because it is a chronic infectious disease that is contagious. Dental caries begins after the primary teeth grow and develop on the tooth surface very quickly and progressively. In recent years the views of neutrophils have changed dramatically. Neutrophils

  19. Increased Epstein–Barr virus in breast milk occurs with subclinical mastitis and HIV shedding

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    Sanosyan, Armen; Rutagwera, David G.; Molès, Jean-Pierre; Bollore, Karine; Peries, Marianne; Kankasa, Chipepo; Mwiya, Mwiya; Tylleskär, Thorkild; Nagot, Nicolas; Van De Perre, Philippe; Tuaillon, Edouard

    2016-01-01

    Abstract Epstein–Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case–control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers. The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples of Zambian mothers participating in the ANRS 12174 trial. Mammary gland inflammation was defined as a breast milk sodium to potassium ratio (Na+/K+) greater than 0.6 and further subclassified as either “possible SCM” (Na+/K+ ratio 0.6–1.0) or SCM (Na+/K+ ratio ≥ 1.0). Breast milk interleukin 8 (IL-8) was measured as a surrogate marker of mammary gland inflammation. EBV DNA was detected in breast milk samples from 42 out of 83 (51%) participants and was associated with HIV-1 shedding in breast milk (P = 0.006). EBV DNA levels were higher in samples with SCM and “possible SCM” compared to non-SCM breast milk samples (P = 0.06; P = 0.007). An EBV DNA level of >200 copies/mL was independently associated with SCM and “possible SCM” (OR: 2.62; 95%: 1.13–6.10). In patients with SCM, higher EBV replication in the mammary gland was associated with a lower induction of IL-8 (P = 0.013). Resistance to DNase treatment suggests that EBV DNA in lactoserum is encapsidated. SCM and decreased IL-8 responses are associated with an increased EBV shedding in breast milk which may in turn facilitate HIV replication in the mammary gland. PMID:27399077

  20. Increased Epstein-Barr virus in breast milk occurs with subclinical mastitis and HIV shedding.

    Science.gov (United States)

    Sanosyan, Armen; Rutagwera, David G; Molès, Jean-Pierre; Bollore, Karine; Peries, Marianne; Kankasa, Chipepo; Mwiya, Mwiya; Tylleskär, Thorkild; Nagot, Nicolas; Van De Perre, Philippe; Tuaillon, Edouard

    2016-07-01

    Epstein-Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case-control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers.The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples of Zambian mothers participating in the ANRS 12174 trial. Mammary gland inflammation was defined as a breast milk sodium to potassium ratio (Na/K) greater than 0.6 and further subclassified as either "possible SCM" (Na/K ratio 0.6-1.0) or SCM (Na/K ratio ≥ 1.0). Breast milk interleukin 8 (IL-8) was measured as a surrogate marker of mammary gland inflammation.EBV DNA was detected in breast milk samples from 42 out of 83 (51%) participants and was associated with HIV-1 shedding in breast milk (P = 0.006). EBV DNA levels were higher in samples with SCM and "possible SCM" compared to non-SCM breast milk samples (P = 0.06; P = 0.007). An EBV DNA level of >200 copies/mL was independently associated with SCM and "possible SCM" (OR: 2.62; 95%: 1.13-6.10). In patients with SCM, higher EBV replication in the mammary gland was associated with a lower induction of IL-8 (P = 0.013). Resistance to DNase treatment suggests that EBV DNA in lactoserum is encapsidated.SCM and decreased IL-8 responses are associated with an increased EBV shedding in breast milk which may in turn facilitate HIV replication in the mammary gland.

  1. Low Tidal Volume Reduces Lung Inflammation Induced by Liquid Ventilation in Piglets With Severe Lung Injury.

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    Jiang, Lijun; Feng, Huizhen; Chen, Xiaofan; Liang, Kaifeng; Ni, Chengyao

    2017-05-01

    Total liquid ventilation (TLV) is an alternative treatment for severe lung injury. High tidal volume is usually required for TLV to maintain adequate CO 2 clearance. However, high tidal volume may cause alveolar barotrauma. We aim to investigate the effect of low tidal volume on pulmonary inflammation in piglets with lung injury and under TLV. After the establishment of acute lung injury model by infusing lipopolysaccharide, 12 piglets were randomly divided into two groups, TLV with high tidal volume (25 mL/kg) or with low tidal volume (6 mL/kg) for 240 min, respectively. Extracorporeal CO 2 removal was applied in low tidal volume group to improve CO 2 clearance and in high tidal volume group as sham control. Gas exchange and hemodynamic status were monitored every 30 min during TLV. At the end of the study, pulmonary mRNA expression and plasmatic concentration of interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured by collecting lung tissue and blood samples from piglets. Arterial blood pressure, PaO 2 , and PaCO 2 showed no remarkable difference between groups during the observation period. Compared with high tidal volume strategy, low tidal volume resulted in 76% reduction of minute volume and over 80% reduction in peak inspiratory pressure during TLV. In addition, low tidal volume significantly diminished pulmonary mRNA expression and plasmatic level of IL-6 and IL-8. We conclude that during TLV, low tidal volume reduces lung inflammation in piglets with acute lung injury without compromising gas exchange. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  2. Hyaluronan minimizes effects of UV irradiation on human keratinocytes.

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    Hašová, Martina; Crhák, Tomáš; Safránková, Barbora; Dvořáková, Jana; Muthný, Tomáš; Velebný, Vladimír; Kubala, Lukáš

    2011-05-01

    Exposure to ultraviolet (UV) irradiation has detrimental effects on skin accompanied by the increased metabolism of hyaluronan (HA), a linear polysaccharide important for the normal physiological functions of skin. In this study, the modulation of human keratinocyte response to UVB irradiation by HA (970 kDa) was investigated. Immortalized human keratinocytes (HaCaT) were irradiated by a single dose of UVB and immediately treated with HA for 6 and 24 h. The irradiation induced a significant decrease in the gene expression of CD44 and toll-like receptor 2 6 h after irradiation. The expressions of other HA receptors, including toll-like receptor 4 and the receptor for HA-mediated motility, were not detected in either the control or UVB-irradiated or HA-treated HaCaT cells. UVB irradiation induced a significant decrease in the gene expression of HA synthase-2 and hyaluronidase-2 6 h after irradiation. The expressions of HA synthase-3 and hyaluronidase-3 were not significantly modulated by UV irradiation. Interestingly, HA treatment did not significantly modulate any of these effects. In contrast, HA significantly suppressed UVB-induced pro-inflammatory cytokine release including interleukin-6 and interleukin-8. Similarly, HA treatment reduced the UVB-mediated production of transforming growth factor β1. HA treatment also significantly reduced the UV irradiation-mediated release of soluble CD44 into the media. Finally, HA partially, but significantly, suppressed the UVB-induced decrease in cell viability. Data indicate that HA had significant protective effects for HaCaT cells against UVB irradiation.

  3. The Effects of Reduced Gluten Barley Diet on Humoral and Cell-Mediated Systemic Immune Responses of Gluten-Sensitive Rhesus Macaques

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    Karol Sestak

    2015-03-01

    Full Text Available Celiac disease (CD affects approximately 1% of the general population while an estimated additional 6% suffers from a recently characterized, rapidly emerging, similar disease, referred to as non-celiac gluten sensitivity (NCGS. The only effective treatment of CD and NCGS requires removal of gluten sources from the diet. Since required adherence to a gluten-free diet (GFD is difficult to accomplish, efforts to develop alternative treatments have been intensifying in recent years. In this study, the non-human primate model of CD/NCGS, e.g., gluten-sensitive rhesus macaque, was utilized with the objective to evaluate the treatment potential of reduced gluten cereals using a reduced gluten (RG; 1% of normal gluten barley mutant as a model. Conventional and RG barleys were used for the formulation of experimental chows and fed to gluten-sensitive (GS and control macaques to determine if RG barley causes a remission of dietary gluten-induced clinical and immune responses in GS macaques. The impacts of the RG barley diet were compared with the impacts of the conventional barley-containing chow and the GFD. Although remission of the anti-gliadin antibody (AGA serum responses and an improvement of clinical diarrhea were noted after switching the conventional to the RG barley diet, production of inflammatory cytokines, e.g., interferon-gamma (IFN-γ, tumor necrosis factor (TNF and interleukin-8 (IL-8 by peripheral CD4+ T helper lymphocytes, persisted during the RG chow treatment and were partially abolished only upon re-administration of the GFD. It was concluded that the RG barley diet might be used for the partial improvement of gluten-induced disease but its therapeutic value still requires upgrading—by co-administration of additional treatments.

  4. Plasma leptin and insulin-like growth factor I levels during acute exacerbations of chronic obstructive pulmonary disease.

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    Kythreotis, Prokopis; Kokkini, Ageliki; Avgeropoulou, Stavrina; Hadjioannou, Argyro; Anastasakou, Efgenia; Rasidakis, Antonis; Bakakos, Petros

    2009-04-05

    Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-alpha). Insulin-like growth factor I (IGF-I) mediates the metabolic effects of growth hormone (GH). The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD). The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I) levels and furthermore, whether these changes are related to systemic inflammation. We measured serum leptin, IGF-I, TNF-alpha, interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and interleukin 8 (IL-8) levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1) and two weeks later (Day 15). 25 healthy age-matched subjects served as controls. COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema). Serum leptin and IGF-I were measured by radioimmunoassay and TNF-alpha, IL-1 beta, IL-6 and IL-8 were measured by ELISA. Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p leptin and TNF-alpha on Day 1 (r = 0.620, p leptin levels along with decreased IGF-I levels occurred during acute exacerbations of COPD. Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later.

  5. Plasma leptin and insulin-like growth factor I levels during acute exacerbations of chronic obstructive pulmonary disease

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    Rasidakis Antonis

    2009-04-01

    Full Text Available Abstract Background Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-α. Insulin-like growth factor I (IGF-I mediates the metabolic effects of growth hormone (GH. The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD. The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I levels and furthermore, whether these changes are related to systemic inflammation. Methods We measured serum leptin, IGF-I, TNF-α, interleukin 1β (IL-1β, interleukin 6 (IL-6 and interleukin 8 (IL-8 levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1 and two weeks later (Day 15. 25 healthy age-matched subjects served as controls. COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema. Serum leptin and IGF-I were measured by radioimmunoassay and TNF-α, IL-1β, IL-6 and IL-8 were measured by ELISA. Results Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p Conclusion Inappropriately increased circulating leptin levels along with decreased IGF-I levels occured during acute exacerbations of COPD. Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later.

  6. Discriminative Accuracy of Novel and Traditional Biomarkers in Children with Suspected Appendicitis Adjusted for Duration of Abdominal Pain

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    Kharbanda, Anupam B.; Cosme, Yohaimi; Liu, Khin; Spitalnik, Steven L.; Dayan, Peter S.

    2011-01-01

    Objectives To assess the accuracy of novel and traditional biomarkers in patients with suspected appendicitis as a function of duration of symptoms. Methods This was a prospective cohort study, conducted in a tertiary care emergency department (ED). The authors enrolled children 3 to 18 years old with acute abdominal pain of less than 96 hours, and measured serum levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), C - reactive protein (CRP), white blood cell count (WBC), and absolute neutrophil count (ANC). Final diagnosis was determined by histopathology or telephone follow-up. Trends in biomarker levels were examined based on duration of abdominal pain. The accuracy of biomarkers was assessed with receiver operating characteristic (ROC) curves. Optimal cut-points and test performance characteristics were calculated for each biomarker. Results Of 280 patients enrolled, the median age was 11.3 years (IQR 8.6 to 14.8), 57% were male, and 33% had appendicitis. Median IL-6, median CRP, mean WBC, and mean ANC differed significantly (p appendicitis and those without appendicitis; median IL-8 levels did not differ between groups. In non-perforated appendicitis, median IL-6, WBC, and ANC levels were maximal at less than 24 hrs of pain, while CRP peaked between 24 and 48 hours. In perforated appendicitis, median IL-8 levels were highest by 24 hours, WBC and IL-6 by 24 to 48 hours, and CRP after 48 hours of pain. The WBC appeared to be the most useful marker to predict appendicitis in those with fewer than 24 or more than 48 hours of pain, while CRP was the most useful in those with 24 to 48 hours of pain. Conclusions In this population, the serum levels and accuracy of novel and traditional biomarkers varies in relation to duration of abdominal pain. IL-6 shows promise as a novel biomarker to identify children with appendicitis. PMID:21676053

  7. Effects of feminine hygiene products on the vaginal mucosal biome

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    Raina N. Fichorova

    2013-02-01

    Full Text Available Background: Over-the-counter (OTC feminine hygiene products come with little warning about possible side effects. This study evaluates in-vitro their effects on Lactobacillus crispatus, which is dominant in the normal vaginal microbiota and helps maintain a healthy mucosal barrier essential for normal reproductive function and prevention of sexually transmitted infections and gynecologic cancer. Methods: A feminine moisturizer (Vagisil, personal lubricant, and douche were purchased OTC. A topical spermicide (nonoxynol-9 known to alter the vaginal immune barrier was used as a control. L. crispatus was incubated with each product for 2 and 24h and then seeded on agar for colony forming units (CFU. Human vaginal epithelial cells were exposed to products in the presence or absence of L. crispatus for 24h, followed by epithelium-associated CFU enumeration. Interleukin-8 was immunoassayed and ANOVA was used for statistical evaluation. Results: Nonoxynol-9 and Vagisil suppressed Lactobacillus growth at 2h and killed all bacteria at 24h. The lubricant decreased bacterial growth insignificantly at 2h but killed all at 24h. The douche did not have a significant effect. At full strength, all products suppressed epithelial viability and all, except the douche, suppressed epithelial-associated CFU. When applied at non-toxic dose in the absence of bacteria, the douche and moisturizer induced an increase of IL-8, suggesting a potential to initiate inflammatory reaction. In the presence of L. crispatus, the proinflammatory effects of the douche and moisturizer were countered, and IL-8 production was inhibited in the presence of the other products. Conclusion: Some OTC vaginal products may be harmful to L. crispatus and alter the vaginal immune environment. Illustrated through these results, L. crispatus is essential in the preservation of the function of vaginal epithelial cells in the presence of some feminine hygiene products. More research should be invested

  8. Tissue-specific transplantation antigen P35B (TSTA3) immune response-mediated metabolism coupling cell cycle to postreplication repair network in no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) by biocomputation.

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    Wang, Lin; Huang, Juxiang; Jiang, Minghu; Lin, Hong

    2012-06-01

    We constructed the low-expression tissue-specific transplantation antigen P35B (TSTA3) immune response-mediated metabolism coupling cell cycle to postreplication repair network in no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) compared with high-expression (fold change ≥ 2) human hepatocellular carcinoma in GEO data set, by using integration of gene regulatory network inference method with gene ontology analysis of TSTA3-activated up- and downstream networks. Our results showed TSTA3 upstream-activated CCNB2, CKS1B, ELAVL3, GAS7, NQO1, NTN1, OCRL, PLA2G1B, REG3A, SSTR5, etc. and TSTA3 downstream-activated BAP1, BRCA1, CCL20, MCM2, MS4A2, NTN1, REG1A, TP53I11, VCAN, SLC16A3, etc. in no-tumor hepatitis/cirrhotic tissues. TSTA3-activated network enhanced the regulation of apoptosis, cyclin-dependent protein kinase activity, cell migration, insulin secretion, transcription, cell division, cell proliferation, DNA replication, postreplication repair, cell differentiation, T-cell homeostasis, neutrophil-mediated immunity, neutrophil chemotaxis, interleukin-8 production, inflammatory response, immune response, B-cell activation, humoral immune response, actin filament organization, xenobiotic metabolism, lipid metabolism, phospholipid metabolism, leukotriene biosynthesis, organismal lipid catabolism, phosphatidylcholine metabolism, arachidonic acid secretion, activation of phospholipase A2, deoxyribonucleotide biosynthesis, heterophilic cell adhesion, activation of MAPK activity, signal transduction by p53 class mediator resulting in transcription of p21 class mediator, G-protein-coupled receptor protein signaling pathway, response to toxin, acute-phase response, DNA damage response, intercellular junction assembly, cell communication, and cell recognition, as a result of inducing immune response-mediated metabolism coupling cell cycle to postreplication repair in no-tumor hepatitis/cirrhotic tissues.

  9. External validation of a biomarker and clinical prediction model for hospital mortality in acute respiratory distress syndrome.

    Science.gov (United States)

    Zhao, Zhiguo; Wickersham, Nancy; Kangelaris, Kirsten N; May, Addison K; Bernard, Gordon R; Matthay, Michael A; Calfee, Carolyn S; Koyama, Tatsuki; Ware, Lorraine B

    2017-08-01

    Mortality prediction in ARDS is important for prognostication and risk stratification. However, no prediction models have been independently validated. A combination of two biomarkers with age and APACHE III was superior in predicting mortality in the NHLBI ARDSNet ALVEOLI trial. We validated this prediction tool in two clinical trials and an observational cohort. The validation cohorts included 849 patients from the NHLBI ARDSNet Fluid and Catheter Treatment Trial (FACTT), 144 patients from a clinical trial of sivelestat for ARDS (STRIVE), and 545 ARDS patients from the VALID observational cohort study. To evaluate the performance of the prediction model, the area under the receiver operating characteristic curve (AUC), model discrimination, and calibration were assessed, and recalibration methods were applied. The biomarker/clinical prediction model performed well in all cohorts. Performance was better in the clinical trials with an AUC of 0.74 (95% CI 0.70-0.79) in FACTT, compared to 0.72 (95% CI 0.67-0.77) in VALID, a more heterogeneous observational cohort. The AUC was 0.73 (95% CI 0.70-0.76) when FACTT and VALID were combined. We validated a mortality prediction model for ARDS that includes age, APACHE III, surfactant protein D, and interleukin-8 in a variety of clinical settings. Although the model performance as measured by AUC was lower than in the original model derivation cohort, the biomarker/clinical model still performed well and may be useful for risk assessment for clinical trial enrollment, an issue of increasing importance as ARDS mortality declines, and better methods are needed for selection of the most severely ill patients for inclusion.

  10. Unexpected Inflammatory Effects of Intravaginal Gels (Universal Placebo Gel and Nonoxynol-9 on the Upper Female Reproductive Tract: A Randomized Crossover Study.

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    Karen Smith-McCune

    Full Text Available Intravaginal anti-HIV microbicides could provide women with a self-controlled means for HIV prevention, but results from clinical trials have been largely disappointing. We postulated that unrecognized effects of intravaginal gels on the upper female reproductive tract might contribute to the lower-than-expected efficacy of HIV microbicides. Our objective was to study the effects of intravaginal gels on the immune microenvironment of the cervix and uterus. In this randomized crossover study, 27 healthy female volunteers used a nightly application of intravaginal nonoxynol-9 (N9 gel as a "failed" microbicide or the universal placebo gel (UPG as a "safe" gel (intervention cycles, or nothing (control cycle from the end of menses to the mid-luteal phase. At a specific time-point following ovulation, all participants underwent sample collection for measurements of T-cell phenotypes, gene expression, and cytokine/chemokine protein concentrations from 3 anatomic sites above the vagina: the cervical transformation zone, the endocervix and the endometrium. We used hierarchical statistical models to estimate mean (95% CI intervention effects, for N9 and UPG relative to control. Exposure to N9 gel and UPG generated a common "harm signal" that included transcriptional up-regulation of inflammatory genes chemokine (C-C motif ligand 20 (macrophage inflammatory factor-3alpha and interleukin 8 in the cervix, decreased protein concentrations of secretory leukocyte protease inhibitor, and transcriptional up-regulation of inflammatory mediators glycodelin-A and osteopontin in the endometrium. These results need to be replicated with a larger sample, but underscore the need to consider the effects of microbicide agents and gel excipients on the upper female reproductive tract in studies of vaginal microbicides.

  11. Current advances in biomarkers for targeted therapy in triple-negative breast cancer

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    Fleisher B

    2016-10-01

    Full Text Available Brett Fleisher,1 Charlotte Clarke,2 Sihem Ait-Oudhia1 1Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, 2Department of Translational Research, UT MD Anderson Cancer Center, Houston, TX, USA Abstract: Triple-negative breast cancer (TNBC is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials.gov. The selected candidate biomarkers were classified as surrogate, prognostic, predictive, or pharmacodynamic (PD and organized by location in the blood, on the cell surface, in the cytoplasm, or in the nucleus. Blood biomarkers include vascular endothelial growth factor/vascular endothelial growth factor receptor and interleukin-8 (IL-­8; cell surface biomarkers include EGFR, insulin-like growth factor binding protein, c-Kit, c-Met, and PD-L1; cytoplasm biomarkers include PIK3CA, pAKT/S6/p4E-BP1, PTEN, ALDH1, and the PIK3CA/AKT/mTOR-related metabolites; and nucleus biomarkers include BRCA1, the glucocorticoid receptor, TP53, and Ki67. Candidate biomarkers were further organized into a “cellular protein network” that demonstrates potential connectivity. This review provides an inventory and reference point for promising biomarkers for breakthrough targeted therapies in TNBC. Keywords: anti-cancer directed pharmacotherapy, difficult

  12. The protective effect of different airway humidification liquids to lung after tracheotomy in traumatic brain injury: The role of pulmonary surfactant protein-A (SP-A).

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    Su, Xinyang; Li, Zefu; Wang, Meilin; Li, Zhenzhu; Wang, Qingbo; Lu, Wenxian; Li, Xiaoli; Zhou, Youfei; Xu, Hongmei

    2016-02-10

    The purpose of this study was to establish a rat model of a brain injury with tracheotomy and compared the wetting effects of different airway humidification liquids, afterward, the best airway humidification liquid was selected for the clinical trial, thus providing a theoretical basis for selecting a proper airway humidification liquid in a clinical setting. Rats were divided into a sham group, group A (0.9% NaCl), group B (0.45% NaCl), group C (0.9% NaCl+ambroxol) and group D (0.9% NaCl+Pulmicort). An established rat model of traumatic brain injury with tracheotomy was used. Brain tissue samples were taken to determine water content, while lung tissue samples were taken to determine wet/dry weight ratio (W/D), histological changes and expression levels of SP-A mRNA and SP-A protein. 30 patients with brain injury and tracheotomy were selected and divided into two groups based on the airway humidification liquid instilled in the trachea tube, 0.45% NaCl and 0.9% NaCl+ambroxol. Blood was then extracted from the patients to measure the levels of SP-A, interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The difference between group C and other groups in lung W/D and expression levels of SP-A mRNA and SP-A protein was significant (Phumidification liquid. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Oxygen With Cold Bubble Humidification Is No Better Than Dry Oxygen in Preventing Mucus Dehydration, Decreased Mucociliary Clearance, and Decline in Pulmonary Function.

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    Franchini, Michelle Lisidati; Athanazio, Rodrigo; Amato-Lourenço, Luis Fernando; Carreirão-Neto, Waldir; Saldiva, Paulo Hilario Nascimento; Lorenzi-Filho, Geraldo; Rubin, Bruce K; Nakagawa, Naomi Kondo

    2016-08-01

    Little is known about the effects of long-term nasal low-flow oxygen (NLFO) on mucus and symptoms and how this variable is affected by dry or cold humidified gas. The aim of this study was to investigate the effects of dry-NLFO and cold bubble humidified-NLFO on nasal mucociliary clearance (MCC), mucus properties, inflammation, and symptoms in subjects with chronic hypoxemia requiring long-term domiciliary oxygen therapy. Eighteen subjects (mean age, 68 years; 7 male; 66% with COPD) initiating NLFO were randomized to receive dry-NLFO (n = 10) or humidified-NLFO (n = 8). Subjects were assessed at baseline, 12 h, 7 days, 30 days, 12 months, and 24 months by measuring nasal MCC using the saccharin transit test, mucus contact angle (surface tension), inflammation (cells and cytokine concentration in nasal lavage), and symptoms according to the Sino-Nasal Outcome Test-20. Nasal MCC decreased significantly (40% longer saccharin transit times) and similarly in both groups over the study period. There was a significant association between impaired nasal MCC and decline in lung function. Nasal lavage revealed an increased proportion of macrophages, interleukin-8, and epidermal growth factor concentrations with decreased interleukin-10 during the study. No changes in the proportion of ciliated cells or contact angle were observed. Coughing and sleep symptoms decreased similarly in both groups. There were no outcome differences comparing dry vs cold bubble humidified NLFO. In subjects receiving chronic NLFO, cold bubble humidification does not adequately humidify inspired oxygen to prevent deterioration of MCC, mucus hydration, and pulmonary function. The unheated bubble humidification performed no better than no humidification. ClinicalTrials.gov; No.: NCT02515786; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  14. A Chip for Estrogen Receptor Action: Detection of Biomarkers Released by MCF-7 Cells through Estrogenic and Anti-Estrogenic Effects

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    Konstanze Gier

    2017-08-01

    Full Text Available The fluorescence-based multi-analyte chip platform for the analysis of estrogenic and anti-estrogenic substances is a new in vitro tool for the high throughput screening of environmental samples. In contrast to existing tools, the chip investigates the complex action of xenoestrogens in a human cell model by characterizing protein expression. It allows for the quantification of 10 proteins secreted by MCF-7 cells, representing various biological and pathological endpoints of endocrine action and distinguishing between estrogen- and anti-estrogen-dependent secretion of proteins. Distinct protein secretion patterns of the cancer cell line after exposure to known estrogen receptor agonists ß-estradiol, bisphenol A, genistein, and nonylphenol as well as antagonists fulvestrant and tamoxifen demonstrate the potential of the chip. Stimulation of cells with Interleukin-1ß shifts concentrations of low abundant biomarkers towards the working range of the chip. In the non-stimulated cell culture, Matrix Metalloproteinase 9 (MMP-9 and Vascular Endothelial Growth Factor (VEGF show differences upon treatment with antagonists and agonists of the estrogen receptor. In stimulated MCF-7 cells challenged with receptor agonists secretion of Monocyte Chemoattractant Protein (MCP-1, Interleukin-6 (IL-6, Rantes, and Interleukin-8 (IL-8 significantly decreases. In parallel, the proliferating effect of endocrine-disrupting substances in MCF-7 cells is assessed in a proliferation assay based on resazurin. Using ethanol as a solvent for test substances increases the background of proliferation and secretion experiments, while using dimethyl sulfoxide (DMSO does not show any adverse effects. The role of the selected biomarkers in different physiological processes such as cell development, reproduction, cancer, and metabolic syndrome makes the chip an excellent tool for either indicating endocrine-disrupting effects in food and environmental samples, or for screening the

  15. Helicobacter hepaticus Induces an Inflammatory Response in Primary Human Hepatocytes

    Science.gov (United States)

    Kleine, Moritz; Worbs, Tim; Schrem, Harald; Vondran, Florian W. R.; Kaltenborn, Alexander; Klempnauer, Jürgen; Förster, Reinhold; Josenhans, Christine; Suerbaum, Sebastian; Bektas, Hüseyin

    2014-01-01

    Helicobacter hepaticus can lead to chronic hepatitis and hepatocellular carcinoma in certain strains of mice. Until now the pathogenic role of Helicobacter species on human liver tissue is still not clarified though Helicobacter species identification in human liver cancer was successful in case controlled studies. Therefore we established an in vitro model to investigate the interaction of primary human hepatocytes (PHH) with Helicobacter hepaticus. Successful co-culturing of PHH with Helicobacter hepaticus was confirmed by visualization of motile bacteria by two-photon-microscopy. Isolated human monocytes were stimulated with PHH conditioned media. Changes in mRNA expression of acute phase cytokines and proteins in PHH and stimulated monocytes were determined by Real-time PCR. Furthermore, cytokines and proteins were analyzed in PHH culture supernatants by ELISA. Co-cultivation with Helicobacter hepaticus induced mRNA expression of Interleukin-1 beta (IL-1β), Tumor necrosis factor-alpha, Interleukin-8 (IL-8) and Monocyte chemotactic protein-1 (MCP-1) in PHH (pmedia (p<0.05). An increase of Cyclooxygenase-2 mRNA expression was observed, with a concomitant increase of prostaglandin E2 concentration in PHH supernatants at 24 and 48 h (p<0.05). In contrast, at day 7 of co-culture, no persistent elevation of cytokine mRNA could be detected. High expression of intercellular adhesion molecule-1 on PHH cell membranes after co-culture was shown by two-photon-microscopy and confirmed by flow-cytomety. Finally, expression of Cytochrome P450 3A4 and albumin mRNA were downregulated, indicating an impairment of hepatocyte synthesis function by Helicobacter hepaticus presence. This is the first in vitro model demonstrating a pathogenic effect of a Helicobacter spp. on human liver cells, resulting in an inflammatory response with increased synthesis of inflammatory mediators and consecutive monocyte activation. PMID:24932686

  16. Impact of Unsaturated Fatty Acids on Cytokine-Driven Endothelial Cell Dysfunction.

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    Trommer, Simon; Leimert, Anja; Bucher, Michael; Schumann, Julia

    2017-12-16

    Polyunsaturated fatty acids (PUFA) are reported to exert prophylactic and acute therapeutic effects in diseases linked to endothelial dysfunction. In the present study, the consequences of a PUFA enrichment of endothelial cells (cell line TIME) on cell viability, expression of the cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein 1 (MCP-1), synthesis of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular adhesion molecule 1 (VCAM-1), and production of the coagulation factors plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), and tissue factor (TF) was analyzed in parallel. PUFA of both the n3 and the n6 family were investigated in a physiologically relevant concentration of 15 µM, and experiments were performed in both the presence and the absence of the pro-inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Supplementation of the culture medium with particular fatty acids was found to have a promoting effect on cellular production of the cytokines IL-6, IL-8, GM-CSF, and MCP-1. Further on, PUFA treatment in the absence of a stimulant diminished the percentage of endothelial cells positive for ICAM-1, and adversely affected the stimulation-induced upregulation of VCAM-1. Cell viability and production of coagulation factors were not or only marginally affected by supplemented fatty acids. Altogether, the data indicate that PUFA of either family are only partially able to counterbalance the destructive consequences of an endothelial dysfunction.

  17. [Attachment style and cytokine levels in patients with fibromyalgia. A prospective longitudinal study].

    Science.gov (United States)

    Wang, H; Weber, A; Schiltenwolf, M; Amelung, D

    2014-10-01

    The association between attachment style and subjective pain is controversially discussed and the influence of attachment styles on cytokine levels in chronic pain has received little attention in research. In this prospective longitudinal clinical study, we evaluated the relationship between cytokines, attachment style and subjective pain intensity as well as pain-related functioning in patients with fibromyalgia (FM) who underwent a 4-week multidisciplinary pain therapy. The attachment style was determined in 43 patients with FM using the relationship questionnaire (RQ-2) and subjective pain with the German version of the West Haven-Yale multidimensional pain inventory. Serum levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 8 (IL-8) and the anti-inflammatory cytokines IL-4 and IL-10 were assessed before and after treatment and additionally once only in 18 healthy controls (Bio-Plex system). Patients with FM syndrome were significantly more often insecurely attached than healthy controls (p = 0.001). Serum levels of TNF-α (p = 0.001) and IL-10 (p = 0.039) were significantly higher in FM patients compared to controls. Attachment was unrelated to IL-4, IL-8, and IL-10 levels. Insecurely attached FM patients had significantly higher levels of TNF-α (p = 0.002). than securely attached patients. Insecurely and securely attached patients did not differ in subjective levels of pain severity, activity or functional interference. Cytokine levels were not correlated with subjective levels of pain severity or functional interference. Multidisciplinary pain therapy significantly reduced cytokine levels, pain severity, anxiety and depression independent of attachment style.

  18. Insulin Like Growth Factor-1 (IGF-1 Causes Overproduction of IL-8, an Angiogenic Cytokine and Stimulates Neovascularization in Isoproterenol-Induced Myocardial Infarction in Rats

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    Nagaraja Haleagrahara

    2011-11-01

    Full Text Available Angiogenesis factors are produced in response to hypoxic or ischemic insult at the site of pathology, which will cause neovascularization. Insulin like growth factor-1 (IGF-1 exerts potent proliferative, angiogenic and anti-apoptotic effects in target tissues. The present study was aimed to evaluate the effects of IGF-1 on circulating level of angiogenic cytokine interleukin-8 (IL-8, in experimentally-induced myocardial ischemia in rats. Male Sprague-Dawley rats were divided into control, IGF-1 treated (2 µg/kg/day subcutaneously, for 5 and 10 days, isoproterenol (ISO treated (85 mg/kg, subcutaneously for two days and ISO with IGF-1 treated (for 5 and 10 days. Heart weight, serum IGF-1, IL-8 and cardiac marker enzymes (CK-MB and LDH were recorded after 5 and 10 days of treatment. Histopathological analyses of the myocardium were also done. There was a significant increase in serum cardiac markers with ISO treatment indicating myocardial infarction in rats. IGF-1 level increased significantly in ISO treated groups and the level of IGF-1 was significantly higher after 10 days of treatment. IL-8 level increased significantly after ISO treatment after 5 and 10 days and IGF-1 concurrent treatment to ISO rats had significantly increased IL-8 levels. Histopathologically, myocyte necrosis and nuclear pyknosis were reduced significantly in IGF-1 treated group and there were numerous areas of capillary sprouting suggestive of neovascularization in the myocardium. Thus, IGF-1 protects the ischemic myocardium with increased production of circulating angiogenic cytokine, IL-8 and increased angiogenesis.

  19. Eggs modulate the inflammatory response to carbohydrate restricted diets in overweight men

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    Volek Jeff S

    2008-02-01

    Full Text Available Abstract Background Carbohydrate restricted diets (CRD consistently lower glucose and insulin levels and improve atherogenic dyslipidemia [decreasing triglycerides and increasing HDL cholesterol (HDL-C]. We have previously shown that male subjects following a CRD experienced significant increases in HDL-C only if they were consuming a higher intake of cholesterol provided by eggs compared to those individuals who were taking lower concentrations of dietary cholesterol. Here, as a follow up of our previous study, we examined the effects of eggs (a source of both dietary cholesterol and lutein on adiponectin, a marker of insulin sensitivity, and on inflammatory markers in the context of a CRD. Methods Twenty eight overweight men [body mass index (BMI 26–37 kg/m2] aged 40–70 y consumed an ad libitum CRD (% energy from CHO:fat:protein = 17:57:26 for 12 wk. Subjects were matched by age and BMI and randomly assigned to consume eggs (EGG, n = 15 (640 mg additional cholesterol/day provided by eggs or placebo (SUB, n = 13 (no additional dietary cholesterol. Fasting blood samples were drawn before and after the intervention to assess plasma lipids, insulin, adiponectin and markers of inflammation including C-reactive protein (CRP, tumor necrosis factor-alpha (TNF-α, interleukin-8 (IL-8, monocyte chemoattractant protein-1 (MCP-1, intercellular adhesion molecule-1 (ICAM-1, and vascular cell adhesion molecule-1(VCAM-1. Results Body weight, percent total body fat and trunk fat were reduced for all subjects after 12 wk (P Conclusion A CRD with daily intake of eggs decreased plasma CRP and increased plasma adiponectin compared to a CRD without eggs. These findings indicate that eggs make a significant contribution to the anti-inflammatory effects of CRD, possibly due to the presence of cholesterol, which increases HDL-C and to the antioxidant lutein which modulates certain inflammatory responses.

  20. Anti-Inflammatory Benefits of Antibiotics: Tylvalosin Induces Apoptosis of Porcine Neutrophils and Macrophages, Promotes Efferocytosis, and Inhibits Pro-Inflammatory CXCL-8, IL1α, and LTB4 Production, While Inducing the Release of Pro-Resolving Lipoxin A4 and Resolvin D1

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    Ruth Moges

    2018-04-01

    Full Text Available Excessive accumulation of neutrophils and their uncontrolled death by necrosis at the site of inflammation exacerbates inflammatory responses and leads to self-amplifying tissue injury and loss of organ function, as exemplified in a variety of respiratory diseases. In homeostasis, neutrophils are inactivated by apoptosis, and non phlogistically removed by neighboring macrophages in a process known as efferocytosis, which promotes the resolution of inflammation. The present study assessed the potential anti-inflammatory and pro-resolution benefits of tylvalosin, a recently developed broad-spectrum veterinary macrolide derived from tylosin. Recent findings indicate that tylvalosin may modulate inflammation by suppressing NF-κB activation. Neutrophils and monocyte-derived macrophages were isolated from fresh blood samples obtained from 12- to 22-week-old pigs. Leukocytes exposed to vehicle or to tylvalosin (0.1, 1.0, or 10 µg/mL; 0.096–9.6 µM were assessed at various time points for apoptosis, necrosis, efferocytosis, and changes in the production of cytokines and lipid mediators. The findings indicate that tylvalosin increases porcine neutrophil and macrophage apoptosis in a concentration- and time-dependent manner, without altering levels of necrosis or reactive oxygen species production. Importantly, tylvalosin increased the release of pro-resolving Lipoxin A4 (LXA4 and Resolvin D1 (RvD1 while inhibiting the production of pro-inflammatory Leukotriene B4 (LTB4 in Ca2+ ionophore-stimulated porcine neutrophils. Tylvalosin increased neutrophil phospholipase C activity, an enzyme involved in releasing arachidonic acid from membrane stores. Tylvalosin also inhibited pro-inflammatory chemokine (C–X–C motif ligand 8 (CXCL-8, also known as Interleukin-8 and interleukin-1 alpha (IL-1α protein secretion in bacterial lipopolysaccharide-stimulated macrophages. Together, these data illustrate that tylvalosin has potent immunomodulatory effects

  1. Rac1 signaling regulates cigarette smoke-induced inflammation in the lung via the Erk1/2 MAPK and STAT3 pathways.

    Science.gov (United States)

    Jiang, Jun-Xia; Zhang, Shui-Juan; Shen, Hui-Juan; Guan, Yan; Liu, Qi; Zhao, Wei; Jia, Yong-Liang; Shen, Jian; Yan, Xiao-Feng; Xie, Qiang-Min

    2017-07-01

    Cigarette smoke (CS) is a major risk factor for the development of chronic obstructive pulmonary disease (COPD). Our previous studies have indicated that Rac1 is involved in lipopolysaccharide-induced pulmonary injury and CS-mediated epithelial-mesenchymal transition. However, the contribution of Rac1 activity to CS-induced lung inflammation remains not fully clear. In this study, we investigated the regulation of Rac1 in CS-induced pulmonary inflammation. Mice or 16HBE cells were exposed to CS or cigarette smoke extract (CSE) to induce acute inflammation. The lungs of mice exposed to CS showed an increase in the release of interleukin-6 (IL-6) and keratinocyte-derived chemokine (KC), as well as an accumulation of inflammatory cells, indicating high Rac1 activity. The exposure of 16HBE cells to CSE resulted in elevated Rac1 levels, as well as increased release of IL-6 and interleukin-8 (IL-8). Selective inhibition of Rac1 ameliorated the release of IL-6 and KC as well as inflammation in the lungs of CS-exposed mice. Histological assessment showed that treatment with a Rac1 inhibitor, NSC23766, led to a decrease in CD68 and CD11b positive cells and the infiltration of neutrophils and macrophages into the alveolar spaces. Selective inhibition or knockdown of Rac1 decreased IL-6 and IL-8 release in 16HBE cells induced by CSE, which correlated with CSE-induced Rac1-regulated Erk1/2 mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription-3 (STAT3) signaling. Our data suggest an important role for Rac1 in the pathological alterations associated with CS-mediated inflammation. Rac1 may be a promising therapeutic target for the treatment of CS-induced pulmonary inflammation. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Effect of steroids on inflammatory markers and clinical parameters in congenital open heart surgery: a randomised controlled trial.

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    Amanullah, Muhammad M; Hamid, Mohammad; Hanif, Hashim M; Muzaffar, Marium; Siddiqui, Maria T; Adhi, Fatima; Ahmad, Khabir; Khan, Shahjahan; Hasan, Zahra

    2016-03-01

    Cardiopulmonary bypass is associated with systemic inflammatory response. Steroids suppress this response, although the therapeutic evidence remains controversial. We hypothesised that intravenous steroids in children undergoing open-heart surgery would decrease inflammation leading to better early post-operative outcomes. We conducted a randomised controlled trial to evaluate the trends in the levels of immunomodulators and their effects on clinical parameters. To assess the effects of intravenous steroids on early post-operative inflammatory markers and clinical parameters in children undergoing open-heart surgery. A randomised controlled trial involving 152 patients, from one month up to 18 years of age, who underwent open-heart surgery for congenital heart disease from April 2010-2012 was carried out. Patients were randomised and administered either three scheduled intravenous pulse doses of dexamethasone (1 mg/kg) or placebo. Blood samples were drawn at four time intervals and serum levels of inflammatory cytokines - Interleukin-6, 8, 10, 18, and tumour necrosis factor-alpha - were measured. Clinical parameters were also assessed. Blood cytokine levels were compared between the dexamethasone (n=65) and placebo (n=64) groups. Interleukin-6 levels were lower at 6 and 24 hours post-operatively (p<0.001), and Interleukin-10 levels were higher 6 hours post-operatively (p<0.001) in the steroid group. Interleukin-8, 18, and tumour necrosis factor-alpha levels did not differ between the groups at any time intervals. The clinical parameters were similar in both the groups. Dexamethasone caused quantitative suppression of Interleukin-6 and increased Interleukin-10 activation, contributing to reduced immunopathology, but it did not translate into clinical benefit in the short term.

  3. Staphylococcal β-Toxin Modulates Human Aortic Endothelial Cell and Platelet Function through Sphingomyelinase and Biofilm Ligase Activities

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    Alfa Herrera

    2017-03-01

    Full Text Available Staphylococcus aureus causes many infections, such as skin and soft tissue, pneumonia, osteomyelitis, and infective endocarditis (IE. IE is an endovascular infection of native and prosthetic valves and the lining of the heart; it is characterized by the formation of cauliflower-like “vegetations” composed of fibrin, platelets, other host factors, bacteria, and bacterial products. β-Toxin is an S. aureus virulence factor that contributes to the microorganism’s ability to cause IE. This cytolysin has two enzymatic activities: sphingomyelinase (SMase and biofilm ligase. Although both activities have functions in a rabbit model of IE, the mechanism(s by which β-toxin directly affects human cells and is involved in the infectious process has not been elucidated. Here, we compared the in vitro effects of purified recombinant wild-type β-toxin, SMase-deficient β-toxin (H289N, and biofilm ligase-deficient β-toxin (H162A and/or D163A on human aortic endothelial cells (HAECs and platelets. β-Toxin was cytotoxic to HAECs and inhibited the production of interleukin 8 (IL-8 from these cells by both SMase and biofilm ligase activities. β-Toxin altered HAEC surface expression of CD40 and vascular cell adhesion molecule 1 (VCAM-1. HAECs treated with β-toxin displayed granular membrane morphology not seen in treatment with the SMase-deficient mutant. The altered morphology resulted in two possibly separable activities, cell rounding and redistribution of cell membranes into granules, which were not the result of endosome production from the Golgi apparatus or lysosomes. β-Toxin directly aggregated rabbit platelets via SMase activity.

  4. Vibrio cholerae cytolysin causes an inflammatory response in human intestinal epithelial cells that is modulated by the PrtV protease.

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    Gangwei Ou

    Full Text Available BACKGROUND: Vibrio cholerae is the causal intestinal pathogen of the diarrheal disease cholera. It secretes the protease PrtV, which protects the bacterium from invertebrate predators but reduces the ability of Vibrio-secreted factor(s to induce interleukin-8 (IL-8 production by human intestinal epithelial cells. The aim was to identify the secreted component(s of V. cholerae that induces an epithelial inflammatory response and to define whether it is a substrate for PrtV. METHODOLOGY/PRINCIPAL FINDINGS: Culture supernatants of wild type V. cholerae O1 strain C6706, its derivatives and pure V. cholerae cytolysin (VCC were analyzed for the capacity to induce changes in cytokine mRNA expression levels, IL-8 and tumor necrosis factor-alpha (TNF-alpha secretion, permeability and cell viability when added to the apical side of polarized tight monolayer T84 cells used as an in vitro model for human intestinal epithelium. Culture supernatants were also analyzed for hemolytic activity and for the presence of PrtV and VCC by immunoblot analysis. CONCLUSIONS/SIGNIFICANCE: We suggest that VCC is capable of causing an inflammatory response characterized by increased permeability and production of IL-8 and TNF-alpha in tight monolayers. Pure VCC at a concentration of 160 ng/ml caused an inflammatory response that reached the magnitude of that caused by Vibrio-secreted factors, while higher concentrations caused epithelial cell death. The inflammatory response was totally abolished by treatment with PrtV. The findings suggest that low doses of VCC initiate a local immune defense reaction while high doses lead to intestinal epithelial lesions. Furthermore, VCC is indeed a substrate for PrtV and PrtV seems to execute an environment-dependent modulation of the activity of VCC that may be the cause of V. cholerae reactogenicity.

  5. The influence of breast milk and infant formulae hydrolysates on bacterial adhesion and Caco-2 cells functioning.

    Science.gov (United States)

    Fiedorowicz, Ewa; Markiewicz, Lidia Hanna; Sidor, Katarzyna; Świątecka, Dominika; Cieślińska, Anna; Matysiewicz, Michał; Piskorz-Ogórek, Krystyna; Sienkiewicz-Szłapka, Edyta; Teodorowicz, Małgorzata; Świątecki, Aleksander; Kostyra, Elżbieta

    2016-11-01

    The aim of the study was to determine the concentration of BCM7 in human milk and infant formulae (IF) before and after eznymatic hydrolysis, and to evaluate the effect of obtained hydrolysates on interleukin-8 (IL-8) secretion and on proliferation of enterocytes in the in vitro model (Caco-2 cells). This study evaluates also the effect of hydrolysates on the adhesion of intestinal microbiota isolated from faeces of both healthy (H) and allergic (A) infants. In the study we investigated breast milk delivered by mothers of healthy ('healthy milk'; HM) and allergic ('allergic milk'; AM) infants. Three infant formulae were investigated: from hydrolysed cow casein (IF1), from hydrolysed cow whey (IF2) and from whole cow milk (IF3). Intestinal bacteria: Bifidobacterium, lactic acid bacteria, Enterobacteriaceae, Clostridium and Enterococcus were isolated from faeces of five healthy and five allergic infants. Mixtures of bacterial isolates and bacteria adhering to Caco-2 cells were characterised qualitatively with PCR-DGGE, and quantitavely with FISH. Concentration of BCM7 in breast milk and infant formulae was 1.6 to 8.9 times higher after enzymatic hydrolysis in comparison to undigested samples. The presence of this peptide resulted in alteration of intestinal epithelial proliferation and increase in secretion of IL-8. The quantitative profile of adherred bacteria applied as a mix of all isolates from healthy infants (H-MIX) was unchanged in the presence of HM hydrolysate and was modulated (increased number of beneficial Bifidobacterium and reduced commensal Enterobacteriaceae) in the presence of all IF hydrolysates. The presence of IF hydrolysates affected the profile of adhering isolates obtained from allergic infants (A-MIX) and reduced the adhesion of Enterobacteriaceae; the IF2 and IF3 hydrolysates decreased also the total number of adhering bacteria (TBN). However, a stimulating effect of AM hydrolysate on A-MIX adhesion (increased TBN) was observed. Copyright

  6. Efficacy of sodium butyrate adjunct therapy in shigellosis: a randomized, double-blind, placebo-controlled clinical trial

    Science.gov (United States)

    2012-01-01

    Background Treatment of shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of shigellosis in patients. Methods A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. Results Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. Conclusion Adjunct therapy with butyrate during shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. Trial Registration Clinical

  7. Effects of dietary inulin, Bacillus subtilis and microalgae on intestinal gene expression in gilthead seabream (Sparus aurata L.).

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    Cerezuela, Rebeca; Meseguer, José; Esteban, M Ángeles

    2013-03-01

    The present work describes effects of dietary inulin, two microalgae (Tetraselmis chuii and Phaeodactylum tricornutum) and Bacillus subtilis (solely or combined with inulin or microalgae) on the expression of different genes in the intestine of the gilthead seabream (Sparus aurata L.) following four weeks of a feeding trial. Selected genes were grouped into five categories: genes involved in inflammation (genes encoding proinflammatory proteins), genes related to the cytoskeleton, genes encoding proteins of junction complexes, genes implicated in digestion processes and genes related to transport proteins. Regarding proinflammatory genes, interleukin-8 (IL-8) expression showed a significant increase in the fish fed all the assayed diets, except the B. subtilis + inulin diet, whereas the expression of caspase-1 (CASP-1) was also increased by the B. subtilis and B. subtilis + T. chuii diets. Cyclooxygenase-2 (COX-2) gene expression only increased in fish fed the B. subtilis diet. Among cytoskeletal and junctional genes, only β-actin and occludin were significantly affected by the assayed diets. β-actin expression was up-regulated by the inulin-containing diets (inulin and B. subtilis + inulin diets), whereas occludin expression increased in the fish fed all the assayed diets, except the P. tricornutum diet. Finally, the expression of transport protein genes demonstrated that the inulin diet and all the experimental diets containing B. subtilis significantly increased transferrin expression, whereas digestive enzymes were not affected by the experimental diets. In conclusion, our results demonstrated that inulin, B. subtilis and microalgae can modulate intestinal gene expression in the gilthead seabream. To our knowledge, this is the first study of the effects of some food additives on the intestinal expression of different genes in this species. More studies are needed to understand the role of these genes in maintaining the integrity and

  8. Melatonin reduces the expression of chemokines in rat with trinitrobenzene sulfonic acid-induced colitis

    International Nuclear Information System (INIS)

    Li, Jun H.; Zhou, W.; Liu, K.; Li, Hong X.; Wang, L.

    2008-01-01

    Objective was to investigate the effect of melatonin on the colon inflammatory injury of rats with colitis and determine whether this effect is associated with inhibition of chemoattractant molecules interleukins (IL-8) and monocyte chemoattractant protein (MCP)-1.The study was designed and implemented in JingMen No.1 People's Hospital, HuBei Province, from May 2006 to April 2007. It involved 72 animals divided into 6 groups of 12 each: normal group, model group, 5-aminosalisalicylic acid group, and melatonin group (dose of 2.5, 5.0 and 10.0mg/kg). Rat colitis model was established by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) enema. Interleukin-8 and MCP-1 proteins in colon tissue were examined by immunohistochemistry and western blot. The messenger-RNA expressions of chemokines were determined by reverse transcription polymerase chain reaction analysis. Trinitrobenzene sulfonic acid enema resulted in pronounced pathological changes of colonic mucosa in model rats, which were in accordance with the significantly elevated Myeloperoxidase activity. Expressions of chemokines were up-regulated in colitis. Melatonin treatment reduced colonic lesions and improved colitis symptom, and decreased the protein and mRNA expressions of IL-8 and MCP-1 significantly in colon tissues of rats with colitis. Chemokines IL-8 and MCP-1 are elevated in mucosal tissues in colitis and play an important role in the perpetuation of tissue destructive inflammatory process; melatonin reduces colonic inflammatory injury of rats colitis through down-regulating the expressions of chemokines. Melatonin can be considered as a novel therapeutic alternative for the treatment of inflammatory bowel disease. (author)

  9. Patterns of circulating inflammatory biomarkers in older persons with varying levels of physical performance: a partial least squares-discriminant analysis approach.

    Science.gov (United States)

    Marzetti, Emanuele; Landi, Francesco; Marini, Federico; Cesari, Matteo; Buford, Thomas W; Manini, Todd M; Onder, Graziano; Pahor, Marco; Bernabei, Roberto; Leeuwenburgh, Christiaan; Calvani, Riccardo

    2014-01-01

    Chronic, low-grade inflammation and declining physical function are hallmarks of the aging process. However, previous attempts to correlate individual inflammatory biomarkers with physical performance in older people have produced mixed results. Given the complexity of the inflammatory response, the simultaneous analysis of an array of inflammatory mediators may provide more insights into the relationship between inflammation and age-related physical function decline. This study was designed to explore the association between a panel of inflammatory markers and physical performance in older adults through a multivariate statistical approach. Community-dwelling older persons were categorized into "normal walkers" (NWs; n = 27) or "slow walkers" (SWs; n = 11) groups using 0.8 m s(-1) as the 4-m gait speed cutoff. A panel of 14 circulating inflammatory biomarkers was assayed by multiplex analysis. Partial least squares-discriminant analysis (PLS-DA) was used to identify patterns of inflammatory mediators associated with gait speed categories. The optimal complexity of the PLS-DA model was found to be five latent variables. The proportion of correct classification was 88.9% for NW subjects (74.1% in cross-validation) and 90.9% for SW individuals (81.8% in cross-validation). Discriminant biomarkers in the model were interleukin 8, myeloperoxidase, and tumor necrosis factor alpha (all higher in the SW group), and P-selectin, interferon gamma, and granulocyte-macrophage colony-stimulating factor (all higher in the NW group). Distinct profiles of circulating inflammatory biomarkers characterize older subjects with different levels of physical performance. The dissection of these patterns may provide novel insights into the role played by inflammation in the disabling cascade and possible new targets for interventions.

  10. Compartment differences of inflammatory activity in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Ji, Jie; von Schéele, Ida; Bergström, Jan; Billing, Bo; Dahlén, Barbro; Lantz, Ann-Sofie; Larsson, Kjell; Palmberg, Lena

    2014-08-26

    Chronic obstructive pulmonary disease (COPD) is associated with local and systemic inflammation. The knowledge of interaction and co-variation of the inflammatory responses in different compartments is meagre. Healthy controls (n = 23), smokers with (n = 28) and without (n = 29) COPD performed spirometry and dental examinations. Saliva, induced sputum, bronchoalveolar lavage (BAL) fluid and serum were collected. Inflammatory markers were assessed in all compartments using ELISA, flow cytometry and RT-PCR. Negative correlations between lung function and saliva IL-8 and matrix metalloproteinase-9 (MMP-9) were found in smokers with COPD. IL-8 and MMP-9 in saliva correlated positively with periodontal disease as assessed by gingival bleeding in non-smokers.Tumor necrosis factor-α (TNF-α) in saliva, serum and TNF-α mRNA expression on macrophages in BAL-fluid were lower in smokers than in non-smokers. There were positive correlations between soluble TNF-α receptor 1 (sTNFR1) and soluble TNF-α receptor 2 (sTNFR2) in sputum, BAL-fluid and serum in all groups. Sputum interleukin-8 (IL-8) or interleukin-6 (IL-6) was positively correlated with sTNFR1 or sTNFR2 in non-smokers and with sTNFR2 in COPD. Saliva which is convenient to collect and analyse, may be suitable for biomarker assessment of disease activity in COPD. An attenuated TNF-α expression was demonstrated by both protein and mRNA analyses in different compartments suggesting that TNF-α response is altered in moderate and severe COPD. Shedding of TNFR1 or TNFR2 is similarly regulated irrespective of airflow limitation.

  11. In vitro biocompatibility of titanium alloy discs made using direct metal fabrication.

    Science.gov (United States)

    Haslauer, Carla Maria; Springer, Jessica Collins; Harrysson, Ola L A; Loboa, Elizabeth G; Monteiro-Riviere, Nancy A; Marcellin-Little, Denis J

    2010-07-01

    Custom orthopedic implants may be generated using free-form fabrication methods (FFF) such as electron beam melting (EBM). EBM FFF may be used to make solid metal implants whose surface is often polished using CNC machining and porous scaffolds that are usually left unpolished. We assessed the in vitro biocompatibility of EBM titanium-6 aluminum-4 vanadium (Ti6Al4V) structures by comparing the cellular response to solid polished, solid unpolished, and porous EBM discs to the cellular response to discs made of commercially produced Ti6Al4V. The discs were seeded with 20,000 human adipose-derived adult stem cells (hASCs) and assessed for cell viability, proliferation, and release of the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8). Cell viability was assessed with Live/Dead staining 8 days after seeding. Cell proliferation was assessed using alamarBlue assays at days 0, 1, 2, 3, and 7. The hASCs were alive on all discs after 8 days. Cellular proliferation on porous EBM discs was increased at days 2, 3, and 7 compared to discs made of commercial Ti6Al4V. Cellular proliferation on porous EBM discs was also increased compared to solid polished and unpolished EBM discs. IL-6 and IL-8 releases at day 7 were lower for porous EBM discs than for other discs. Solid polished, unpolished, and porous EBM Ti6Al4V discs exhibited an acceptable biocompatibility profile compared to solid Ti6Al4V discs from a commercial source. EBM FFF may be considered as an option for the fabrication of custom orthopedic implants. Copyright 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

  12. Soybean β-conglycinin induces inflammation and oxidation and causes dysfunction of intestinal digestion and absorption in fish.

    Science.gov (United States)

    Zhang, Jin-Xiu; Guo, Lin-Ying; Feng, Lin; Jiang, Wei-Dan; Kuang, Sheng-Yao; Liu, Yang; Hu, Kai; Jiang, Jun; Li, Shu-Hong; Tang, Ling; Zhou, Xiao-Qiu

    2013-01-01

    β-Conglycinin has been identified as one of the major feed allergens. However, studies of β-conglycinin on fish are scarce. This study investigated the effects of β-conglycinin on the growth, digestive and absorptive ability, inflammatory response, oxidative status and gene expression of juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and their enterocytes in vitro. The results indicated that the specific growth rate (SGR), feed intake, and feed efficiency were reduced by β-conglycinin. In addition, activities of trypsin, chymotrypsin, lipase, creatine kinase, Na(+),K(+)-ATPase and alkaline phosphatase in the intestine showed similar tendencies. The protein content of the hepatopancreas and intestines, and the weight and length of the intestines were all reduced by β-conglycinin. β-Conglycinin increased lipid and protein oxidation in the detected tissues and cells. However, β-conglycinin decreased superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and glutathione (GSH) content in the intestine and enterocytes. Similar antioxidant activity in the hepatopancreas was observed, except for GST. The expression of target of rapamycin (TOR) gene was reduced by β-conglycinin. Furthermore, mRNA levels of interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) genes were increased by β-conglycinin. However, β-conglycinin increased CuZnSOD, MnSOD, CAT, and GPx1b gene expression. In conclusion, this study indicates that β-conglycinin induces inflammation and oxidation, and causes dysfunction of intestinal digestion and absorption in fish, and finally reduces fish growth. The results of this study provide some information to the mechanism of β-conglycinin-induced negative effects.

  13. Soybean β-conglycinin induces inflammation and oxidation and causes dysfunction of intestinal digestion and absorption in fish.

    Directory of Open Access Journals (Sweden)

    Jin-Xiu Zhang

    Full Text Available β-Conglycinin has been identified as one of the major feed allergens. However, studies of β-conglycinin on fish are scarce. This study investigated the effects of β-conglycinin on the growth, digestive and absorptive ability, inflammatory response, oxidative status and gene expression of juvenile Jian carp (Cyprinus carpio var. Jian in vivo and their enterocytes in vitro. The results indicated that the specific growth rate (SGR, feed intake, and feed efficiency were reduced by β-conglycinin. In addition, activities of trypsin, chymotrypsin, lipase, creatine kinase, Na(+,K(+-ATPase and alkaline phosphatase in the intestine showed similar tendencies. The protein content of the hepatopancreas and intestines, and the weight and length of the intestines were all reduced by β-conglycinin. β-Conglycinin increased lipid and protein oxidation in the detected tissues and cells. However, β-conglycinin decreased superoxide dismutase (SOD, catalase (CAT, glutathione-S-transferase (GST, glutathione peroxidase (GPx and glutathione reductase (GR activities and glutathione (GSH content in the intestine and enterocytes. Similar antioxidant activity in the hepatopancreas was observed, except for GST. The expression of target of rapamycin (TOR gene was reduced by β-conglycinin. Furthermore, mRNA levels of interleukin-8 (IL-8, tumor necrosis factor-α (TNF-α, and transforming growth factor-β (TGF-β genes were increased by β-conglycinin. However, β-conglycinin increased CuZnSOD, MnSOD, CAT, and GPx1b gene expression. In conclusion, this study indicates that β-conglycinin induces inflammation and oxidation, and causes dysfunction of intestinal digestion and absorption in fish, and finally reduces fish growth. The results of this study provide some information to the mechanism of β-conglycinin-induced negative effects.

  14. The type III secretion effector NleF of enteropathogenic Escherichia coli activates NF-κB early during infection.

    Science.gov (United States)

    Pallett, Mitchell A; Berger, Cedric N; Pearson, Jaclyn S; Hartland, Elizabeth L; Frankel, Gad

    2014-11-01

    The enteric pathogens enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli employ a type 3 secretion system (T3SS) to manipulate the host inflammatory response during infection. Previously, it has been reported that EPEC, in a T3SS-dependent manner, induces an early proinflammatory response through activation of NF-κB via extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase Cζ (PKCζ). However, the activation of NF-κB during infection has not yet been attributed to an effector. At later time points postinfection, NF-κB signaling is inhibited through the translocation of multiple effectors, including NleE and NleC. Here we report that the highly conserved non-LEE (locus of enterocyte effacement)-encoded effector F (NleF) shows both diffuse and mitochondrial localization during ectopic expression. Moreover, NleF induces the nuclear translocation of NF-κB p65 and the expression of interleukin 8 (IL-8) following ectopic expression and during EPEC infection. Furthermore, the proinflammatory activity and localization of NleF were dependent on the C-terminal amino acids LQCG. While the C-terminal domain of NleF has previously been shown to be essential for interaction with caspase-4, caspase-8, and caspase-9, the proinflammatory activity of NleF was independent of interaction with caspase-4, -8, or -9. In conclusion, EPEC, through the T3SS-dependent translocation of NleF, induces a proinflammatory response in an NF-κB-dependent manner in the early stages of infection. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. The function of TLR4 in interferon gamma or interleukin-13 exposed and lipopolysaccharide stimulated gingival epithelial cell cultures.

    Science.gov (United States)

    Beklen, A; Sarp, A S; Uckan, D; Tsaous Memet, G

    2014-10-01

    Gingival epithelial cells are part of the first line of host defense against infection. Toll-like receptors (TLRs) serve important immune and nonimmune functions. We investigated how interferon gamma (INF-γ) and interleukin 13 (IL-13) are involved in the TLR4 ligand-induced regulation of interleukin-8 (IL-8) effects on gingival epithelial cells. We used immunohistochemistry to localize TLR4 in ten healthy and ten periodontitis tissue specimens. Gingival epithelial cells then were primed with Th1 cytokine (INF-γ) or Th2 cytokine (IL-13) before stimulation with Escherichia coli-derived lipopolysaccharide (LPS) and enzyme-linked immunosorbent assay (ELISA) was performed to detect the level of IL-8 secretion in cell culture supernatants. Although both healthy and periodontitis gingival tissue samples expressed TLR4, the periodontitis samples showed more intense expression on gingival epithelial cells. Gingival epithelial cell cultures were primed with either INF-γ or IL-13 before stimulation with TLR4 ligand. Supernatants from co-stimulated epithelial cells exhibited IL-8 production in opposite directions, i.e., as one stimulates the release, the other reduces the release. INF-γ significantly increased TLR4 function, whereas IL-13 significantly decreased TLR4 function, i.e., production of IL-8. Pathogen associated molecular pattern-LPS, shared by many different periodonto-pathogenic bacteria, activates the gingival epithelial cells in a TLR-dependent manner. Diminished or increased TLR function in gingival epithelial cells under the influence of different Th cell types may protect or be harmful due to the altered TLR signaling.

  16. The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis.

    Science.gov (United States)

    Frayman, Katherine B; Armstrong, David S; Carzino, Rosemary; Ferkol, Thomas W; Grimwood, Keith; Storch, Gregory A; Teo, Shu Mei; Wylie, Kristine M; Ranganathan, Sarath C

    2017-12-01

    In infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of early cystic fibrosis lung disease remains uncertain. To assess the development of the lower airway microbiota over time in infants and young children with cystic fibrosis, and to explore its association with airway inflammation and pulmonary function at age 6 years. Serial, semi-annual bronchoscopies and bronchoalveolar lavage (BAL) procedures were performed in infants newly diagnosed with cystic fibrosis following newborn screening. Quantitative microbiological cultures and inflammatory marker (interleukin 8 and neutrophil elastase) measurements were undertaken contemporaneously. 16S ribosomal RNA gene sequencing was conducted on stored BAL samples. Spirometry results recorded at 6 years of age were extracted from medical records. Ninety-five BAL samples provided 16S ribosomal RNA gene data. These were collected from 48 subjects aged 1.2-78.3 months, including longitudinal samples from 27 subjects and 13 before age 6 months. The lower airway microbiota varied, but diversity decreased with advancing age. Detection of recognised cystic fibrosis bacterial pathogens was associated with reduced microbial diversity and greater lower airway inflammation. There was no association between the lower airway microbiota and pulmonary function at age 6 years. In infants with cystic fibrosis, the lower airway microbiota is dynamic. Dominance of the microbiota by recognised cystic fibrosis bacterial pathogens is associated with increased lower airway inflammation, however early microbial diversity is not associated with pulmonary function at 6 years of age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: The focus of this study was to characterize a novel biomarker for cystic fibrosis (CF) that could reflect exacerbations of the disease and could be useful for therapeutic stratification of patients, or for testing of potential drug treatments. This study focused exclusively on a protein complex containing alpha-1 antitrypsin and CD16b (AAT:CD16b) which is released into the bloodstream from membranes of pro-inflammatory primed neutrophils. METHODS: Neutrophil membrane expression and extracellular levels of AAT and CD16b were quantified by flow cytometry, Western blot analysis and by 2D-PAGE. Interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and AAT:CD16b complex were quantified in CF plasma (n=38), samples post antibiotic treatment for 14days (n=10), chronic obstructive pulmonary disease (n=10), AAT deficient (n=10) and healthy control (n=14) plasma samples by ELISA. RESULTS: Cell priming with IL-8 and TNF-alpha caused release of the AAT:CD16b complex from the neutrophil cell membrane. Circulating plasma levels of IL-8, TNF-alpha and AAT:CD16b complex were significantly higher in patients with CF than in the other patient groups or healthy controls (P<0.05). Antibiotic treatment of pulmonary exacerbation in patients with CF led to decreased plasma protein concentrations of AAT:CD16b complex with a significant correlation with improved FEV1 (r=0.81, P=0.003). CONCLUSION: The results of this study have shown that levels of AAT:CD16b complex present in plasma correlate to the inflammatory status of patients. The AAT:CD16b biomarker may become a useful addition to the clinical diagnosis of exacerbations in CF.

  18. Characterizing microbiota-independent effects of oligosaccharides on intestinal epithelial cells: insight into the role of structure and size : Structure-activity relationships of non-digestible oligosaccharides.

    Science.gov (United States)

    Akbari, Peyman; Fink-Gremmels, Johanna; Willems, Rianne H A M; Difilippo, Elisabetta; Schols, Henk A; Schoterman, Margriet H C; Garssen, Johan; Braber, Saskia

    2017-08-01

    The direct effects of galacto-oligosaccharides (GOS), including Vivinal ® GOS syrup (VGOS) and purified Vivinal ® GOS (PGOS), on the epithelial integrity and corresponding interleukin-8 (IL-8/CXCL8) release were examined in a Caco-2 cell model for intestinal barrier dysfunction. To investigate structure-activity relationships, the effects of individual DP fractions of VGOS were evaluated. Moreover, the obtained results with GOS were compared with Caco-2 monolayers incubated with fructo-oligosaccharides (FOS) and inulin. Caco-2 monolayers were pretreated (24 h) with or without specific oligosaccharides or DP fractions of VGOS (DP2 to DP6) before being exposed for 12 or 24 h to the fungal toxin deoxynivalenol (DON). Transepithelial electrical resistance and lucifer yellow permeability were measured to investigate barrier integrity. A calcium switch assay was used to study the reassembly of tight junction proteins. Release of CXCL8, a typical marker for inflammation, was quantified by ELISA. In comparison with PGOS, FOS and inulin, VGOS showed the most pronounced protective effect on the DON-induced impairment of the monolayer integrity, acceleration of the tight junction reassembly and the subsequent CXCL8 release. DP2 and DP3 in concentrations occurring in VGOS prevented the DON-induced epithelial barrier disruption, which could be related to their high prevalence in VGOS. However, no effects of the separate DP GOS fractions were observed on CXCL8 release. This comparative study demonstrates the direct, microbiota-independent effects of oligosaccharides on the intestinal barrier function and shows the differences between individual galacto- and fructo-oligosaccharides. This microbiota-independent effect of oligosaccharides depends on the oligosaccharide structure, DP length and concentration.

  19. Interleukins in preeclampsia

    International Nuclear Information System (INIS)

    Olusi, Samuel O.; Diejomahoh, M.; Omu, A.; Abdulaziz, A.; Prabha, K.; George, S.

    2000-01-01

    Preeclampsia is a multisystemic disorder of unknown etiology. Recently,endothelial damage has been implicated in its cause. The objective of thisstudy was to determine the role of interleukins in the etiology ofpreeclampsia. 32 primigravidas with preeclampsia but without any clinicalevidence of infection and 32 age-matched primigravidas with uncomplicatednormal pregnancies were investigated. Phlebotomy was performed at 32 weeks ofgestation and blood collected for immunoassay of interleukin-2 (IL-2),interleukin-2 receptor (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8)andvinterleukin-10 (IL-10), using commercially available immunoassay kits.Although the maternal plasma concentrations of IL-2 and IL-2R were slightlyhigher in normal pregnant women (76.3+-13.7 pg/mL and 526+-47.1pg/mL,respectively) than in women with preeclampsia (57.8+-1.08 pg/mL and476.9+-3.9pg/mL, respectively), the difference was not statistically significant(P>0.05). However, maternal plasma IL-6 and IL-8 concentrations weresignificantly higher (P<0.05) in normal pregnancy (158.0+-35.4 pg/mL and5163.6+- 800pg/mL, respectively) than in pregnancy complicated withpreeclampsia (60.0+-13.7 pg/mL and 2495.8+-729 pg/mL, respectively). On thepther hand, maternal plasma concentration of IL-10 was significantly higher(P<0.05) in preeclampsia (93.2+-24.1 pg/mL) than in normal pregnancy(31.0+-7.0 pg/mL). It is concluded that the elevated maternal plasma IL-10concentration in preeclampsia may be protective response to maternalimmunorejection. (author)

  20. Mucosal prevalence and interactions with the epithelium indicate commensalism of Sutterella spp.

    Directory of Open Access Journals (Sweden)

    Kaisa Hiippala

    2016-10-01

    Full Text Available Sutterella species have been frequently associated with human diseases, such as autism, Down syndrome and inflammatory bowel disease (IBD, but the impact of these bacteria on health still remains unclear. Especially the interactions of Sutterella spp. with the host are largely unknown, despite of the species being highly prevalent. In this study, we addressed the interaction of three known species of Sutterella with the intestinal epithelium and examined their adhesion properties, the effect on intestinal barrier function and the pro-inflammatory capacity in vitro. We also studied the relative abundance and prevalence of the genus Sutterella and S. wadsworthensis in intestinal biopsies of healthy individuals and patients with celiac disease (CeD or IBD. Our results show that Sutterella spp. are abundant in the duodenum of healthy adults with a decreasing gradient towards the colon. No difference was detected in the prevalence of Sutterella between the pediatric IBD or CeD patients and the healthy controls. Sutterella parvirubra adhered better than the two other Sutterella spp. to differentiated Caco-2 cells and was capable of decreasing the adherence of S. wadsworthensis, which preferably bound to mucus and human extracellular matrix (ECM proteins. Furthermore, only S. wadsworthensis induced an interleukin-8 (IL-8 production in enterocytes, which could be due to different lipopolysaccharide (LPS structures between the species. However, its pro-inflammatory activity was modest as compared to non-pathogenic Escherichia coli. Sutterella spp. had no effect on the enterocyte monolayer integrity in vitro. Our findings indicate that the members of genus Sutterella are widely prevalent commensals with mild pro-inflammatory capacity in the human gastrointestinal tract and do not contribute significantly to the disrupted epithelial homeostasis associated with microbiota dysbiosis and increase of Proteobacteria. The ability of Sutterella spp. to adhere to

  1. Whole-transcriptome brain expression and exon-usage profiling in major depression and suicide: evidence for altered glial, endothelial and ATPase activity.

    Science.gov (United States)

    Pantazatos, S P; Huang, Y-Y; Rosoklija, G B; Dwork, A J; Arango, V; Mann, J J

    2017-05-01

    Brain gene expression profiling studies of suicide and depression using oligonucleotide microarrays have often failed to distinguish these two phenotypes. Moreover, next generation sequencing approaches are more accurate in quantifying gene expression and can detect alternative splicing. Using RNA-seq, we examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in the dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden death medication-free individuals post mortem. Using small RNA-seq, we also examined miRNA expression (nine samples per group). DeSeq2 identified 35 genes differentially expressed between groups and surviving adjustment for false discovery rate (adjusted Pdepression, altered genes include humanin-like-8 (MTRNRL8), interleukin-8 (IL8), and serpin peptidase inhibitor, clade H (SERPINH1) and chemokine ligand 4 (CCL4), while exploratory gene ontology (GO) analyses revealed lower expression of immune-related pathways such as chemokine receptor activity, chemotaxis and cytokine biosynthesis, and angiogenesis and vascular development in (adjusted Psuicide and depression, and provisional evidence for altered DNA-dependent ATPase expression in suicide only. DEXSEq analysis identified differential exon usage in ATPase, class II, type 9B (adjusted Pdepression. Differences in miRNA expression or structural gene variants were not detected. Results lend further support for models in which deficits in microglial, endothelial (blood-brain barrier), ATPase activity and astrocytic cell functions contribute to MDD and suicide, and identify putative pathways and mechanisms for further study in these disorders.

  2. Microparticles engineered to highly express peroxisome proliferator-activated receptor-γ decreased inflammatory mediator production and increased adhesion of recipient monocytes.

    Directory of Open Access Journals (Sweden)

    Julie Sahler

    Full Text Available Circulating blood microparticles are submicron vesicles released primarily by megakaryocytes and platelets that act as transcellular communicators. Inflammatory conditions exhibit elevated blood microparticle numbers compared to healthy conditions. Direct functional consequences of microparticle composition, especially internal composition, on recipient cells are poorly understood. Our objective was to evaluate if microparticle composition could impact the function of recipient cells, particularly during inflammatory provocation. We therefore engineered the composition of megakaryocyte culture-derived microparticles to generate distinct microparticle populations that were given to human monocytes to assay for influences recipient cell function. Herein, we tested the responses of monocytes exposed to either control microparticles or microparticles that contain the anti-inflammatory transcription factor, peroxisome proliferator-activated receptor-γ (PPARγ. In order to normalize relative microparticle abundance from two microparticle populations, we implemented a novel approach that utilizes a Nanodrop Spectrophotometer to assay for microparticle density rather than concentration. We found that when given to peripheral blood mononuclear cells, microparticles were preferentially internalized by CD11b+ cells, and furthermore, microparticle composition had a profound functional impact on recipient monocytes. Specifically, microparticles containing PPARγ reduced activated monocyte production of the proinflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared to activated monocytes exposed to control microparticles. Additionally, treatment with PPARγ microparticles greatly increased monocyte cell adherence. This change in morphology occurred simultaneously with increased production of the key extracellular matrix protein, fibronectin and increased expression of the fibronectin-binding integrin, ITGA5. PPARγ microparticles

  3. The effects of colloids or crystalloids on acute respiratory distress syndrome in swine (Sus scrofa models with severe sepsis: analysis on extravascular lung water, IL-8, and VCAM-1

    Directory of Open Access Journals (Sweden)

    Rismala Dewi

    2016-04-01

    Full Text Available Background: Acute respiratory distress syndrome (ARDS is a fatal complication of severe sepsis. Due to its higher molecular weight, the use of colloids in fluid resuscitation may be associated with fewer cases of ARDS compared to crystalloids. Extravascular lung water (EVLW elevation and levels of interleukin-8 (IL-8 and vascular cell adhesion molecule-1 (VCAM-1 have been studied as indicators playing a role in the pathogenesis of ARDS. The aim of the study was to determine the effects of colloid or crystalloid on the incidence of ARDS, elevation of EVLW, and levels of IL-8 and VCAM-1, in swine models with severe sepsis.Methods: This was a randomized trial conducted at the Laboratory of Experimental Surgery, School of Veterinary Medicine, IPB, using 22 healthy swine models with a body weight of 8 to 12 kg. Subjects were randomly allocated to receive either colloid or crystalloid fluid resuscitation. After administration of endotoxin, clinical signs of ARDS, EVLW, IL-8, and VCAM-1 were monitored during sepsis, severe sepsis, and one- and three hours after fluid resuscitation. Analysis of data using the Wilcoxon test , Kolmogorov-Smirnov test, Mann-Whitney test, unpaired t test.Results: Mild ARDS was more prevalent in the colloid group, while moderate ARDS was more frequent in the crystalloid group. EVLW elevation was lower in the colloid compared to the crystalloid group. There was no significant difference in IL-8 and VCAM-1 levels between the two groups.Conclusion: The use of colloids in fluid resuscitation does not decrease the probability of ARDS events compared to crystalloids. Compared to crystalloids, colloids are associated with a lower increase in EVLWI, but not with IL-8 or VCAM-1 levels.

  4. Carotenoids, inflammation, and oxidative stress--implications of cellular signaling pathways and relation to chronic disease prevention.

    Science.gov (United States)

    Kaulmann, Anouk; Bohn, Torsten

    2014-11-01

    Several epidemiologic studies have shown that diets rich in fruits and vegetables reduce the risk of developing several chronic diseases, such as type 2 diabetes, atherosclerosis, and cancer. These diseases are linked with systemic, low-grade chronic inflammation. Although controversy persists on the bioactive ingredients, several secondary plant metabolites have been associated with these beneficial health effects. Carotenoids represent the most abundant lipid-soluble phytochemicals, and in vitro and in vivo studies have suggested that they have antioxidant, antiapoptotic, and anti-inflammatory properties. Recently, many of these properties have been linked to the effect of carotenoids on intracellular signaling cascades, thereby influencing gene expression and protein translation. By blocking the translocation of nuclear factor κB to the nucleus, carotenoids are able to interact with the nuclear factor κB pathway and thus inhibit the downstream production of inflammatory cytokines, such as interleukin-8 or prostaglandin E2. Carotenoids can also block oxidative stress by interacting with the nuclear factor erythroid 2-related factor 2 pathway, enhancing its translocation into the nucleus, and activating phase II enzymes and antioxidants, such as glutathione-S-transferases. In this review, which is organized into in vitro, animal, and human investigations, we summarized current knowledge on carotenoids and metabolites with respect to their ability to modulate inflammatory and oxidative stress pathways and discuss potential dose-health relations. Although many pathways involved in the bioactivity of carotenoids have been revealed, future research should be directed toward dose-response relations of carotenoids, their metabolites, and their effect on transcription factors and metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Recruitment of myeloid and plasmacytoid dendritic cells in cervical mucosa during Chlamydia trachomatis infection.

    Science.gov (United States)

    Agrawal, T; Vats, V; Wallace, P K; Singh, A; Salhan, S; Mittal, A

    2009-01-01

    The mobilization of myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) to the cervix during chlamydial infection is not fully understood, and the role of these cells in immunopathogenesis is largely unknown. As an effective vaccine to control chlamydial infection is currently unavailable, understanding the regulation of the local immune response becomes a necessity. Therefore, mDC and pDC populations were analysed in peripheral blood and cervical samples of controls and Chlamydia-positive women, with or without mucopurulent cervicitis (MPC). Cervical cytokines and C-reactive protein levels in serum were quantified by ELISA and the chlamydial infectious load by culture. Chlamydia trachomatis infection mobilized both mDCs and pDCs to the cervical mucosa. pDCs were recruited more often in women with MPC (p cervical interleukin-8 (IL-8) levels. Upregulation of surface expression of co-stimulatory molecules (CD80, CD83 and CD86) on cervical mDCs and pDCs was observed during chlamydial infection but was significant only for mDCs. Significantly higher levels of IL-1 beta, IL-6 and IL-8 were observed in Chlamydia-positive women with MPC; however, after therapy, IL-8 levels decreased significantly. Median numbers of mDCs after therapy were significantly higher in the cervix and blood of infected women as compared to the numbers of pDCs, which were found to be lower in the cervix after therapy. These results thus suggest that during chlamydial infection, both mDCs and pDCs are recruited to the cervix, but their number and possible immunological functions may differ with the pathological condition. pDCs were associated more often with MPC and inflammatory factors, suggesting that they may possibly be involved in the immunopathogenesis of infections due to Chlamydia.

  6. Characterization of pro-inflammatory flagellin proteins produced by Lactobacillus ruminis and related motile Lactobacilli.

    Directory of Open Access Journals (Sweden)

    B Anne Neville

    Full Text Available Lactobacillus ruminis is one of at least twelve motile but poorly characterized species found in the genus Lactobacillus. Of these, only L. ruminis has been isolated from mammals, and this species may be considered as an autochthonous member of the gastrointestinal microbiota of humans, pigs and cows. Nine L. ruminis strains were investigated here to elucidate the biochemistry and genetics of Lactobacillus motility. Six strains isolated from humans were non-motile while three bovine isolates were motile. A complete set of flagellum biogenesis genes was annotated in the sequenced genomes of two strains, ATCC25644 (human isolate and ATCC27782 (bovine isolate, but only the latter strain produced flagella. Comparison of the L. ruminis and L. mali DSM20444(T motility loci showed that their genetic content and gene-order were broadly similar, although the L. mali motility locus was interrupted by an 11.8 Kb region encoding rhamnose utilization genes that is absent from the L. ruminis motility locus. Phylogenetic analysis of 39 motile bacteria indicated that Lactobacillus motility genes were most closely related to those of motile carnobacteria and enterococci. Transcriptome analysis revealed that motility genes were transcribed at a significantly higher level in motile L. ruminis ATCC27782 than in non-motile ATCC25644. Flagellin proteins were isolated from L. ruminis ATCC27782 and from three other Lactobacillus species, while recombinant flagellin of aflagellate L. ruminis ATCC25644 was expressed and purified from E. coli. These native and recombinant Lactobacillus flagellins, and also flagellate L. ruminis cells, triggered interleukin-8 production in cultured human intestinal epithelial cells in a manner suppressed by short interfering RNA directed against Toll-Like Receptor 5. This study provides genetic, transcriptomic, phylogenetic and immunological insights into the trait of flagellum-mediated motility in the lactobacilli.

  7. Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival

    International Nuclear Information System (INIS)

    Eftang, Lars L; Esbensen, Ying; Tannæs, Tone M; Blom, Gustav P; Bukholm, Ida RK; Bukholm, Geir

    2013-01-01

    The genetic changes in gastric adenocarcinoma are extremely complex and reliable tumor markers have not yet been identified. There are also remarkable geographical differences in the distribution of this disease. Our aim was to identify the most differentially regulated genes in 20 gastric adenocarcinomas from a Norwegian selection, compared to matched normal mucosa, and we have related our findings to prognosis, survival and chronic Helicobacter pylori infection. Biopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 20 patients immediately following surgical resection of the tumor. Whole genome, cDNA microarray analysis was performed on the RNA isolated from the sample pairs to compare the gene expression profiles between the tumor against matched mucosa. The samples were microscopically examined to classify gastritis. The presence of H. pylori was examined using microscopy and immunohistochemistry. 130 genes showed differential regulation above a predefined cut-off level. Interleukin-8 (IL-8) and Claudin-1 (CLDN1) were the most consistently up-regulated genes in the tumors. Very high CLDN1 expression in the tumor was identified as an independent and significant predictor gene of reduced post-operative survival. There were distinctly different expression profiles between the tumor group and the control mucosa group, and the histological subsets of mixed type, diffuse type and intestinal type cancer demonstrated further sub-clustering. Up-regulated genes were mapped to cell-adhesion, collagen-related processes and angiogenesis, whereas normal intestinal functions such as digestion and excretion were associated with down-regulated genes. We relate the current findings to our previous study on the gene response of gastric epithelial cells to H. pylori infection. CLDN1 was highly up-regulated in gastric cancer, and CLDN1 expression was independently associated with a poor post-operative prognosis, and may have important prognostic

  8. Crosstalk between Helicobacter pylori and gastric epithelial cells is impaired by docosahexaenoic acid.

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    Marta Correia

    Full Text Available H. pylori colonizes half of the world's population leading to gastritis, ulcers and gastric cancer. H. pylori strains resistant to antibiotics are increasing which raises the need for alternative therapeutic approaches. Docosahexaenoic acid (DHA has been shown to decrease H. pylori growth and its associated-inflammation through mechanisms poorly characterized. We aimed to explore DHA action on H. pylori-mediated inflammation and adhesion to gastric epithelial cells (AGS and also to identify bacterial structures affected by DHA. H. pylori growth and metabolism was assessed in liquid cultures. Bacterial adhesion to AGS cells was visualized by transmission electron microscopy and quantified by an Enzyme Linked Immunosorbent Assay. Inflammatory proteins were assessed by immunoblotting in infected AGS cells, previously treated with DHA. Bacterial total and outer membrane protein composition was analyzed by 2-dimensional gel electrophoresis. Concentrations of 100 µM of DHA decreased H. pylori growth, whereas concentrations higher than 250 µM irreversibly inhibited bacteria survival. DHA reduced ATP production and adhesion to AGS cells. AGS cells infected with DHA pre-treated H. pylori showed a 3-fold reduction in Interleukin-8 (IL-8 production and a decrease of COX2 and iNOS. 2D electrophoresis analysis revealed that DHA changed the expression of H. pylori outer membrane proteins associated with stress response and metabolism and modified bacterial lipopolysaccharide phenotype. As conclusions our results show that DHA anti-H. pylori effects are associated with changes of bacteria morphology and metabolism, and with alteration of outer membrane proteins composition, that ultimately reduce the adhesion of bacteria and the burden of H. pylori-related inflammation.

  9. The role of perivascular adipose tissue in vascular smooth muscle cell growth.

    Science.gov (United States)

    Miao, Chao-Yu; Li, Zhi-Yong

    2012-02-01

    Adipose tissue is the largest endocrine organ, producing various adipokines and many other substances. Almost all blood vessels are surrounded by perivascular adipose tissue (PVAT), which has not received research attention until recently. This review will discuss the paracrine actions of PVAT on the growth of underlying vascular smooth muscle cells (VSMCs). PVAT can release growth factors and inhibitors. Visfatin is the first identified growth factor derived from PVAT. Decreased adiponectin and increased tumour necrosis factor-α in PVAT play a pathological role for neointimal hyperplasia after endovascular injury. PVAT-derived angiotensin II, angiotensin 1-7, reactive oxygen species, complement component 3, NO and H(2) S have a paracrine action on VSMC contraction, endothelial or fibroblast function; however, their paracrine actions on VSMC growth remain to be directly verified. Factors such as monocyte chemoattractant protein-1, interleukin-6, interleukin-8, leptin, resistin, plasminogen activator inhibitor type-1, adrenomedullin, free fatty acids, glucocorticoids and sex hormones can be released from adipose tissue and can regulate VSMC growth. Most of them have been verified for their secretion by PVAT; however, their paracrine functions are unknown. Obesity, vascular injury, aging and infection may affect PVAT, causing adipocyte abnormality and inflammatory cell infiltration, inducing imbalance of PVAT-derived growth factors and inhibitors, leading to VSMC growth and finally resulting in development of proliferative vascular disease, including atherosclerosis, restenosis and hypertension. In the future, using cell-specific gene interventions and local treatments may provide definitive evidence for identification of key factor(s) involved in PVAT dysfunction-induced vascular disease and thus may help to develop new therapies. This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http

  10. Proinflammatory cytokines and DHEA-S in women with fibromyalgia: impact of psychological distress and menopausal status

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    Sturgeon JA

    2014-12-01

    Full Text Available John A Sturgeon,1 Beth D Darnall,1 Heather L Zwickey,2 Lisa J Wood,3 Douglas A Hanes,2 David T Zava,4 Sean C Mackey1 1Stanford University School of Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Palo Alto, CA, USA; 2Helfgott Research Institute, National College of Natural Medicine, Portland, OR, USA; 3MGH Institute of Health Professions, Boston, MA, USA; 4ZRT Laboratories, Beaverton, OR, USA Abstract: Though fibromyalgia is not traditionally considered an inflammatory disorder, evidence for elevated inflammatory processes has been noted in this disorder in multiple studies. Support for inflammatory markers in fibromyalgia has been somewhat equivocal to date, potentially due to inattention to salient patient characteristics that may affect inflammation, such as psychiatric distress and aging milestones like menopause. The current study examined the relationships between proinflammatory cytokines and hormone levels, pain intensity, and psychological distress in a sample of 34 premenopausal and postmenopausal women with fibromyalgia. Our results indicated significant relationships between interleukin-8 and ratings of pain catastrophizing (r=0.555, P<0.05, pain anxiety (r=0.559, P<0.05, and depression (r=0.551, P<0.05 for postmenopausal women but not premenopausal women (r<0.20 in all cases. Consistent with previous studies, ratios of interleukin-6 to interleukin-10 were significantly lower in individuals with greater levels of depressive symptoms (r=−0.239, P<0.05. Contrary to previous research, however, dehydroepiandrosterone sulfate did not correlate with pain intensity or psychological or biological variables. The results of the current study highlight the importance of psychological functioning and milestones of aging in the examination of inflammatory processes in fibromyalgia. Keywords: fibromyalgia, cytokines, psychological distress, inflammation

  11. Circulating Chemokine Levels in Febrile Infants With Serious Bacterial Infections

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    Hsiu-Lin Chen

    2009-12-01

    Full Text Available Early diagnosis of serious bacterial infections (SBI in febrile young infants based on clinical symptoms and signs is difficult. This study aimed to evaluate the diagnostic values of circulating chemokines and C-reactive protein (CRP levels in febrile young infants < 3 months of age with suspected SBI. We enrolled 43 febrile young infants < 3 months of age with clinically suspected SBI who were admitted to the neonatal intensive care unit or complete nursing unit of the pediatric department of Kaohsiung Medical University Hospital between December 2006 and July 2007. Blood was drawn from the patients at admission, and complete blood counts, plasma levels of CRP, granulocyte colony-stimulating factor (G-CSF, and chemokines, including interleukin-8 (IL-8, macrophage inflammatory protein-1α, macrophage inflammatory protein-1β, monokine induced by interferon-γ, and monocyte chemotactic protein-1 were measured. Patients’ symptoms and signs, length of hospital stay, main diagnosis, and results of routine blood tests and microbiological culture results were recorded. Twenty-six infants (60.5% were diagnosed with SBI, while 17 (39.5% had no evidence of SBI based on the results of bacterial cultures. CRP, IL-8 and G-CSF levels were significantly higher in the infants with SBI than in those without SBI. Plasma levels of other chemokines were not significantly different between the groups. The area under the receiver-operating characteristic (ROC curve for differentiating between the presence and absence of SBI was 0.79 for CRP level. Diagnostic accuracy was further improved by combining CRP and IL-8, when the area under the ROC curve increased to 0.91. CRP levels were superior to IL-8 and G-CSF levels for predicting SBI in febrile infants at initial survey. IL-8 levels could be used as an additional diagnostic tool in the initial evaluation of febrile young infants, allowing clinicians to treat these patients more appropriately.

  12. Biocompatible micro-sized cell culture chamber for the detection of nanoparticle-induced IL8 promoter activity on a small cell population

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    Oostingh Gertie

    2011-01-01

    Full Text Available Abstract In most conventional in vitro toxicological assays, the response of a complete cell population is averaged, and therefore, single-cell responses are not detectable. Such averaging might result in misinterpretations when only individual cells within a population respond to a certain stimulus. Therefore, there is a need for non-invasive in vitro systems to verify the toxicity of nanoscale materials. In the present study, a micro-sized cell culture chamber with a silicon nitride membrane (0.16 mm2 was produced for cell cultivation and the detection of specific cell responses. The biocompatibility of the microcavity chip (MCC was verified by studying adipogenic and neuronal differentiation. Thereafter, the suitability of the MCC to study the effects of nanoparticles on a small cell population was determined by using a green fluorescence protein-based reporter cell line. Interleukin-8 promoter (pIL8 induction, a marker of an inflammatory response, was used to monitor immune activation. The validation of the MCC-based method was performed using well-characterized gold and silver nanoparticles. The sensitivity of the new method was verified comparing the quantified pIL8 activation via MCC-based and standard techniques. The results proved the biocompatibility and the sensitivity of the microculture chamber, as well as a high optical quality due to the properties of Si3N4. The MCC-based method is suited for threshold- and time-dependent analysis of nanoparticle-induced IL8 promoter activity. This novel system can give dynamic information at the level of adherent single cells of a small cell population and presents a new non-invasive in vitro test method to assess the toxicity of nanomaterials and other compounds. PACS: 85.35.Be, 81.16.Nd, 87.18.Mp

  13. Biocompatible micro-sized cell culture chamber for the detection of nanoparticle-induced IL8 promoter activity on a small cell population

    Science.gov (United States)

    Kohl, Yvonne; Oostingh, Gertie J.; Sossalla, Adam; Duschl, Albert; von Briesen, Hagen; Thielecke, Hagen

    2011-08-01

    In most conventional in vitro toxicological assays, the response of a complete cell population is averaged, and therefore, single-cell responses are not detectable. Such averaging might result in misinterpretations when only individual cells within a population respond to a certain stimulus. Therefore, there is a need for non-invasive in vitro systems to verify the toxicity of nanoscale materials. In the present study, a micro-sized cell culture chamber with a silicon nitride membrane (0.16 mm2) was produced for cell cultivation and the detection of specific cell responses. The biocompatibility of the microcavity chip (MCC) was verified by studying adipogenic and neuronal differentiation. Thereafter, the suitability of the MCC to study the effects of nanoparticles on a small cell population was determined by using a green fluorescence protein-based reporter cell line. Interleukin-8 promoter (pIL8) induction, a marker of an inflammatory response, was used to monitor immune activation. The validation of the MCC-based method was performed using well-characterized gold and silver nanoparticles. The sensitivity of the new method was verified comparing the quantified pIL8 activation via MCC-based and standard techniques. The results proved the biocompatibility and the sensitivity of the microculture chamber, as well as a high optical quality due to the properties of Si3N4. The MCC-based method is suited for threshold- and time-dependent analysis of nanoparticle-induced IL8 promoter activity. This novel system can give dynamic information at the level of adherent single cells of a small cell population and presents a new non-invasive in vitro test method to assess the toxicity of nanomaterials and other compounds. PACS: 85.35.Be, 81.16.Nd, 87.18.Mp

  14. The Circulating Levels of Selenium, Zinc, Midkine, Some Inflammatory Cytokines, and Angiogenic Factors in Mitral Chordae Tendineae Rupture.

    Science.gov (United States)

    Aydemir, Birsen; Akdemir, Ramazan; Vatan, M Bulent; Cinemre, F Behice; Cinemre, Hakan; Kiziler, Ali Riza; Bahtiyar, Nurten; Buyukokuroglu, M Emin; Gurol, Gonul; Ogut, Selim

    2015-10-01

    Chordae tendineae rupture process is associated with increased production of inflammatory and angiogenesis mediators in connective tissues, which contributes to chronic inflammation and pathogenesis of degenerative chordae. A few trace elements are known to possess antioxidant, anti-inflammatory, and antiangiogenic properties. Therefore, the aim of this study was to determine whether zinc, selenium, midkine (MK), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor-A (VEGF-A), platelet-derived growth factor-BB (PDGF-BB), and reduced glutathione (GSH) levels are associated with inflammation and angiogenesis processes in the context of a potential etiology causing aggravation of mitral regurgitation and/or ruptured chordae tendineae. Seventy-one subjects comprising 34 patients with mitral chordae tendineae rupture (MCTR) and 37 healthy controls diagnosed on the basis of their clinical profile and transthoracic echocardiography were included in this study. The levels of GSH, MK, selenium, and zinc were found to be lower in the patients group when compared to control group. There were no significant difference in plasma TNF-α, IL-1β, IL-6, IL-8, VEGF-A, and PDGF-BB levels between two groups. There were positive significant correlations between MK and GSH, MK, and selenium levels in patients with MCTR. According to our data in which selenium, zinc, MK, and GSH decreased in MCTR patients, inflammatory response, oxidative stress, and trace element levels may contribute to etiopathogenesis of mitral regurgitation and/or ruptured chordae tendineae.

  15. Effect of intramammary infusion of recombinant bovine GM-CSF and IL-8 on CMT score, somatic cell count, and milk mononuclear cell populations in Holstein cows with Staphylococcus aureus subclinical mastitis.

    Science.gov (United States)

    Kiku, Yoshio; Ozawa, Tomomi; Takahashi, Hideyuki; Kushibiki, Shiro; Inumaru, Shigeki; Shingu, Hiroyuki; Nagasawa, Yuya; Watanabe, Atsushi; Hata, Eiji; Hayashi, Tomohito

    2017-09-01

    The effect of intramammary infusion of recombinant bovine granulocyte-macrophage colony-stimulating factor (rbGM-CSF) and interleukin-8 (rbIL-8) on mononuclear cell populations in quarters, somatic cell count (SCC) and the California Mastitis Test (CMT) score were investigated. From the selected cows with naturally occurring Staphylococcus aureus subclinical mastitis, one quarter of each cow were selected for the infusions of rbGM-CSF (400 μg/5 mL/quarter, n = 9), rbIL-8 (1 mg/5 mL/quarter, n = 9), and phosphate-buffered saline (5 mL/quarter, n = 7). The CMT score of both cytokines post infusion temporarily increased between days 0 and 1 and significantly decreased between days 7 and 14 compared to the preinfusion level. The SCC on day 14 after infusions of rbGM-CSF tended to be lower than that of the control group. The percentage of CD14+ cells increased on days 1 and 2 post infusion of rbGM-CSF. The percentage of CD4+ and CD8+ cells also increased on days 2 and 3, suggesting that the infusion of rbGM-CSF enhanced cellular immunity in the mammary gland. In contrast, the percentage of CD14+ cells decreased on days 0.25 and 1 post infusion of rbIL-8. No significant changes in the percentages of CD4+ and CD8+ cells in milk after infusion of rbIL-8 were evident during the experimental period, which suggested that rbIL-8 had little effect on the function of T cells in the mammary gland. These results indicated that rbGM-CSF and rbIL-8 decreased the CMT score by a different mechanism and may have a potential as therapeutic agents for subclinical mastitis.

  16. Alcohol and red wine consumption, but not fruit, vegetables, fish or dairy products, are associated with less endothelial dysfunction and less low-grade inflammation: the Hoorn Study.

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    van Bussel, B C T; Henry, R M A; Schalkwijk, C G; Dekker, J M; Nijpels, G; Feskens, E J M; Stehouwer, C D A

    2017-03-27

    Endothelial dysfunction and low-grade inflammation are key phenomena in the pathobiology of cardiovascular disease (CVD). Their dietary modification might explain the observed reduction in CVD that has been associated with a healthy diet rich in fruit, vegetables and fish, low in dairy products and with moderate alcohol and red wine consumption. We investigated the associations between the above food groups and endothelial dysfunction and low-grade inflammation in a population-based cohort of Dutch elderly individuals. Diet was measured by food frequency questionnaire (n = 801; women = 399; age 68.5 ± 7.2 years). Endothelial dysfunction was determined (1) by combining von Willebrand factor, and soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, endothelial selectin and thrombomodulin, using Z-scores, into a biomarker score and (2) by flow-mediated vasodilation (FMD), and low-grade inflammation by combining C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumour necrosis factor α and sICAM-1 into a biomarker score, with smaller FMD and higher scores representing more dysfunction and inflammation, respectively. We used linear regression analyses to adjust associations for sex, age, energy, glucose metabolism, body mass index, smoking, prior CVD, educational level, physical activity and each of the other food groups. Moderate [β (95% CI) -0.13 (-0.33; 0.07)] and high [-0.22 (-0.45; -0.003)] alcohol consumption, and red wine [-0.16 (-0.30; -0.01)] consumption, but none of the other food groups, were associated with a lower endothelial dysfunction biomarker score and a greater FMD. The associations for FMD were, however, not statistically significant. Only red wine consumption was associated with a lower low-grade inflammation biomarker score [-0.18 (-0.33; -0.04)]. Alcohol and red wine consumption may favourably influence processes involved in atherothrombosis.

  17. Rapid label-free profiling of oral cancer biomarker proteins using nano-UPLC-Q-TOF ion mobility mass spectrometry.

    Science.gov (United States)

    Nassar, Ala F; Williams, Brad J; Yaworksy, Dustin C; Patel, Vyomesh; Rusling, James F

    2016-03-01

    It has become quite clear that single cancer biomarkers cannot in general provide high sensitivity and specificity for reliable clinical cancer diagnostics. This paper explores the feasibility of rapid detection of multiple biomarker proteins in model oral cancer samples using label-free protein relative quantitation. MS-based label-free quantitative proteomics offer a rapid alternative that bypasses the need for stable isotope containing compounds to chemically bind and label proteins. Total protein content in oral cancer cell culture conditioned media was precipitated, subjected to proteolytic digestion, and then analyzed using a nano-UPLC (where UPLC is ultra-performance liquid chromatography) coupled to a hybrid Q-Tof ion-mobility mass spectrometry (MS). Rapid, simultaneous identification and quantification of multiple possible cancer biomarker proteins was achieved. In a comparative study between cancer and noncancer samples, approximately 952 proteins were identified using a high-throughput 1D ion mobility assisted data independent acquisition (IM-DIA) approach. As we previously demonstrated that interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGF-A) were readily detected in oral cancer cell conditioned media(1), we targeted these biomarker proteins to validate our approach. Target biomarker protein IL-8 was found between 3.5 and 8.8 fmol, while VEGF-A was found at 1.45 fmol in the cancer cell media. Overall, our data suggest that the nano-UPLC-IM-DIA bioassay is a feasible approach to identify and quantify proteins in complex samples without the need for stable isotope labeling. These results have significant implications for rapid tumor diagnostics and prognostics by monitoring proteins such as IL-8 and VEGF-A implicated in cancer development and progression. The analysis in tissue or plasma is not possible at this time, but the subsequent work would be needed for validation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Immunomodulation of antiretroviral drug-suppressed chronic HIV-1 infection in an oral probiotic double-blind placebo-controlled trial.

    Science.gov (United States)

    Yang, Otto O; Kelesidis, Theodoros; Cordova, Robert; Khanlou, Homayoon

    2014-10-01

    A putative source of inappropriate immune activation that drives human immunodeficiency virus (HIV)-1 immunopathogenesis is the gastrointestinal tract. Even with effective antiretroviral treatment, residual activation persists. We hypothesized that an oral probiotic could improve the residual immune activation in chronic treated HIV-1 infection, and tested a Bacillus coagulans GBI-30, 6086 capsule probiotic in HIV-1-infected persons with suppressed viremia on stable antiretroviral therapy in a 3-month double-blind placebo-controlled trial (10 probiotic, 7 placebo). The Gastrointestinal Symptom Rating Scale (GSRS) was administered monthly. Blood was tested at the start and end of placebo/probiotic administration for viremia, CD4(+) T cell percentage/concentration, soluble (s)CD14, soluble intestinal fatty acid binding protein, sCD163, D-dimer, C-reactive protein (CRP), interleukin-8, and tumor necrosis factor-α. All participants maintained viremia probiotic was safe and well tolerated, and appeared to improve chronic gastrointestinal symptoms. Its administration was associated with a significant increase in the percentage of blood CD4(+) T cells compared to placebo (+2.8% versus -1.8%, p=0.018) although CD4(+) T cell concentrations were generally unchanged in both groups. None of the biomarkers showed significant changes on probiotic treatment or between-group differences in change (although significance was borderline for a greater sCD163 drop in the probiotic versus placebo group, p=0.05). Some biomarkers showed significant correlations to each other, particularly D-dimer with CRP and sCD14 with tumor necrosis factor (TNF)-α. These data demonstrate the safety and possible benefit of this probiotic for residual inflammation in treated HIV-1 infection, although further study will be required to determine the immune pathways involved.

  19. MiR-124 down-regulation is critical for cancer associated fibroblasts-enhanced tumor growth of oral carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xia, E-mail: dentistlx@163.com [Department of Stomatology, School of Stomatology and medicine, Foshan Stomatology Hospital, Foshan University, Foshan 528000 (China); Fan, Qinqiao [Department of Hepatobiliary Surgery, Cancer Center, Chenzhou No.1 People' s Hospital, Chenzhou 423000 (China); Li, Jinyun [Department of Head and Neck Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Center South University, Changsha 410013 (China); Song, Jing; Gu, Yangcong [Department of Stomatology, School of Stomatology and medicine, Foshan Stomatology Hospital, Foshan University, Foshan 528000 (China)

    2017-02-01

    Cancer associated fibroblasts (CAFs) are known to be involved in initiation, progression and metastasis of various cancers. However, the molecular mechanism of how CAFs affects the biological function of oral cancer (OC) has not been fully-addressed. In this study, we demonstrated that miR-124 was downregulated in oral CAFs and oral cancer cells (OCCs) when compared with matched normal fibroblasts (NFs). Hypermethylation in the promoter region of miR-124 genes was accounted for its downregulation. Interestingly, CAFs but not NFs exerted promotion effect on OCCs cell proliferation, migration and tumor growth in CAFs/NFs-OCCs co-culture. Furthermore, we identified Chemokine (C-C motif) ligand 2 (CCL2) and Interleukin 8 (IL-8) as two direct targets of miR-124. Over-expression of miR-124 in CAFs-OCCs co-culture abrogated CAFs-promoted OCCs cell growth and migration, and this inhibitory effect can be rescued by addition of CCL2 and IL-8. Finally, we showed that restoration of miR-124 expression by lentiviral infection or formulated miR-124 injection inhibited oral tumor growth in vivo suggesting miR-124 rescue could be a potential rationale for therapeutic applications in oral cancer in the future. - Highlights: • miR-124 was downregulated in oral cancer cells and cancer associated fibroblasts. • Hypermethylation in the promoter region was accounted for miR-124 downregulation. • CCL2 and IL-8 are two direct targets of miR-124. • miR-124 rescue could be a potential rationale for oral cancer therapy.

  20. Pulmonary surfactant coating of multi-walled carbon nanotubes (MWCNTs influences their oxidative and pro-inflammatory potential in vitro

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    Gasser Michael

    2012-05-01

    Full Text Available Abstract Background Increasing concern has been expressed regarding the potential adverse health effects that may be associated with human exposure to inhaled multi-walled carbon nanotubes (MWCNTs. Thus it is imperative that an understanding as to the underlying mechanisms and the identification of the key factors involved in adverse effects are gained. In the alveoli, MWCNTs first interact with the pulmonary surfactant. At this interface, proteins and lipids of the pulmonary surfactant bind to MWCNTs, affecting their surface characteristics. Aim of the present study was to investigate if the pre-coating of MWCNTs with pulmonary surfactant has an influence on potential adverse effects, upon both (i human monocyte derived macrophages (MDM monocultures, and (ii a sophisticated in vitro model of the human epithelial airway barrier. Both in vitro systems were exposed to MWCNTs either pre-coated with a porcine pulmonary surfactant (Curosurf or not. The effect of MWCNTs surface charge was also investigated in terms of amino (−NH2 and carboxyl (−COOH surface modifications. Results Pre-coating of MWCNTs with Curosurf affects their oxidative potential by increasing the reactive oxygen species levels and decreasing intracellular glutathione depletion in MDM as well as decreases the release of Tumour necrosis factor alpha (TNF-α. In addition, an induction of apoptosis was observed after exposure to Curosurf pre-coated MWCNTs. In triple cell-co cultures the release of Interleukin-8 (IL-8 was increased after exposure to Curosurf pre-coated MWCNTs. Effects of the MWCNTs functionalizations were minor in both MDM and triple cell co-cultures. Conclusions The present study clearly indicates that the pre-coating of MWCNTs with pulmonary surfactant more than the functionalization of the tubes is a key factor in determining their ability to cause oxidative stress, cytokine/chemokine release and apoptosis. Thus the coating of nano-objects with pulmonary

  1. Dose-Dependent Responses of I3C and DIM on T-Cell Activation in the Human T Lymphocyte Jurkat Cell Line

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    Man Liu

    2017-07-01

    Full Text Available Indole-3-carbinol (I3C and its dimer diindolylmethane (DIM are bioactive metabolites of a glucosinolate, glucobrassicin, found in cruciferous vegetables. Both I3C and DIM have been reported to possess pro-apoptotic, anti-proliferative and anti-carcinogenic properties via modulation of immune pathways. However, results from these studies remain inconclusive since they lack thorough evaluation of these bioactives’ physiological versus pharmacological effects. In the present study, we investigated I3C and DIM’s dose-dependent effects on cytokines production in human T lymphocytes Jurkat cell line (Clone E6-1. The results showed that I3C and DIM pretreatment, at higher concentrations of 50 and 10 μM, respectively, significantly increased PMA/ionomycin-induced interleukin-2 (IL-2, interleukin-8 (IL-8 and tumor necrosis factor-α (TNF-α production, measured by real time polymerase chain reaction (RT-PCR and enzyme linked immunosorbent assay (ELISA. As a plausible mechanism underlying such pronounced cytokine release, we found robust increase in downstream nuclear factor κB (NF-κB and nuclear factor of activated T-cells 1 (NFAT1 signaling with I3C pretreatment, whereas DIM pretreatment only significantly induced NF-κB activation, but not NFAT1. We hypothesize that I3C/DIM pretreatment primes the T cells to become hyperresponsive upon PMA/ionomycin stimulation which in turn differentially induces two major downstream Ca2+-dependent inflammatory pathways, NF-κB and NFAT1. Our data show novel insights into the mechanisms underlying induction of pro-inflammatory cytokine release by pharmacological concentrations of I3C and DIM, an effect negligible under physiological conditions.

  2. Anti-inflammatory activity of silymarin in patients with knee osteoarthritis

    International Nuclear Information System (INIS)

    Hussain, Saad A.; Numan, Intesar T.; Al-Khalifa, Ihab I.; Jassim, Nizar A.; Abdullah, Talal A.

    2009-01-01

    Objective was to evaluate the anti-inflammatory effect of Silymarin in patients with knee osteoarthritis (OA) in comparison with piroxicam and meloxicam. A double-blind clinical trial was performed at the Department of Rheumatology, Baghdad Teaching Hospital, Iraq during the period from October 2004 to September 2005, in which 220 patients (79 males and 141 females) with painful knee osteoarthritis were randomized into 5 groups, treated with either silymarin (300mg/day), piroxicam (20mg/day), meloxicam (15mg) or a combination of silymarin with piroxicam or meloxicam. Serum levels of interleukin-1 alpha, interleukin-8 and the complement proteins C3 and C4 were assessed at zero time and after 8 weeks. Silymarin reduces significantly serum levels of IL-1 alpha and IL-8, C3 and C4 after 8 weeks compared to the pre-treatment levels, while IL-8 decreased significantly, compared to pre-treatment value. Meloxicam elevates serum levels of IL-1 alpha significantly, IL-8 did not significantly change compared to the pre-treatment value. Piroxicam or meloxicam produced slight, non-significant increase in serum levels of complement proteins after the 8-week treatment period. Adjunct use of silymarin with piroxicam results in significant reduction in both cytokines (IL-1 alpha and IL-8) and serum levels of C3 and C4. However, its adjunct use with, meloxicam did not reveal any significant changes in this respect. Silymarin reduces the elevated levels of interleukins and complement proteins, when used alone, or in combination with NSAIDs for treatment of knee OA. (author)

  3. Oxidative stress and inflammatory response to printer toner particles in human epithelial A549 lung cells.

    Science.gov (United States)

    Könczöl, Mathias; Weiß, Adilka; Gminski, Richard; Merfort, Irmgard; Mersch-Sundermann, Volker

    2013-02-04

    Reports on adverse health effects related to occupational exposure to toner powder are still inconclusive. Therefore, we have previously conducted an in vitro-study to characterize the genotoxic potential of three commercially available black printer toner powders in A549 lung cells. In these cell-based assays it was clearly demonstrated that the tested toner powders damage DNA and induce micronucleus (MN) formation. Here, we have studied the cytotoxic and proinflammatory potential of these three types of printer toner particles and the influence of ROS and NF-κB induction in order to unravel the underlying mechanisms. A549 cells were exposed to various concentrations of printer toner particle suspensions for 24 h. The toner particles were observed to exert significant cytotoxic effects in the WST-1 and neutral red (NR)-