Transcriptional profiles of cytokine/chemokine factors of immune cell-homing to the parasitic lesions: a comprehensive one-year course study in the liver of E. multilocularis-infected mice.

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Junhua Wang

Full Text Available Pathogenesis of chronically developing alveolar echinococcosis (AE is characterized by a continuous, granulomatous, periparasitic infiltration of immune cells surrounding the metacestode of Echinococcus multilocularis (E.multilocularis in the affected liver. A detailed cytokine and chemokine profile analysis of the periparasitic infiltrate in the liver has, however, not yet been carried out in a comprehensive way all along the whole course of infection in E. multilocularis intermediate hosts. We thus assessed the hepatic gene expression profiles of 18 selected cytokine and chemokine genes using qRT-PCR in the periparasitic immune reaction and the subsequent adjacent, not directly affected, liver tissue of mice from day 2 to day 360 post intra-hepatic injection of metacestode. DNA microarray analysis was also used to get a more complete picture of the transcriptional changes occurring in the liver surrounding the parasitic lesions. Profiles of mRNA expression levels in the hepatic parasitic lesions showed that a mixed Th1/Th2 immune response, characterized by the concomitant presence of IL-12α, IFN-γ and IL-4, was established very early in the development of E. multilocularis. Subsequently, the profile extended to a combined tolerogenic profile associating IL-5, IL-10 and TGF-β. IL-17 was permanently expressed in the liver, mostly in the periparasitic infiltrate; this was confirmed by the increased mRNA expression of both IL-17A and IL-17F from a very early stage, with a subsequent decrease of IL-17A after this first initial rise. All measured chemokines were significantly expressed at a given stage of infection; their expression paralleled that of the corresponding Th1, Th2 or Th17 cytokines. In addition to giving a comprehensive insight in the time course of cytokines and chemokines in E. multilocularis lesion, this study contributes to identify new targets for possible immune therapy to minimize E. multilocularis-related pathology and to

Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors.

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Amable, Paola Romina; Carias, Rosana Bizon Vieira; Teixeira, Marcus Vinicius Telles; da Cruz Pacheco, Italo; Corrêa do Amaral, Ronaldo José Farias; Granjeiro, José Mauro; Borojevic, Radovan

2013-06-07

Platelet-rich plasma (PRP) is nowadays widely applied in different clinical scenarios, such as orthopedics, ophthalmology and healing therapies, as a growth factor pool for improving tissue regeneration. Studies into its clinical efficiency are not conclusive and one of the main reasons for this is that different PRP preparations are used, eliciting different responses that cannot be compared. Platelet quantification and the growth factor content definition must be defined in order to understand molecular mechanisms behind PRP regenerative strength. Standardization of PRP preparations is thus urgently needed. PRP was prepared by centrifugation varying the relative centrifugal force, temperature, and time. Having quantified platelet recovery and yield, the two-step procedure that rendered the highest output was chosen and further analyzed. Cytokine content was determined in different fractions obtained throughout the whole centrifugation procedure. Our method showed reproducibility when applied to different blood donors. We recovered 46.9 to 69.5% of total initial platelets and the procedure resulted in a 5.4-fold to 7.3-fold increase in platelet concentration (1.4 × 10(6) to 1.9 × 10(6) platelets/μl). Platelets were highly purified, because only platelets after activation with calcium and calcium/thrombin. High concentrations of platelet-derived growth factor, endothelial growth factor and transforming growth factor (TGF) were secreted, together with the anti-inflammatory and proinflammatory cytokines interleukin (IL)-4, IL-8, IL-13, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-α. No cytokines were secreted before platelet activation. TGF-β3 and IFNγ were not detected in any studied fraction. Clots obtained after platelet coagulation retained a high concentration of several growth factors, including platelet-derived growth factor and TGF. Our study resulted in a consistent PRP preparation method that yielded a cytokine and growth factor pool

Effect of Cell Seeding Density and Inflammatory Cytokines on Adipose Tissue-Derived Stem Cells: an in Vitro Study

NARCIS (Netherlands)

Sukho, P. (Panithi); J. Kirpensteijn (Jolle); Hesselink, J.W. (Jan Willem); G.J.V.M. van Osch (Gerjo); F. Verseijden (Femke); Y.M. Bastiaansen-Jenniskens (Yvonne)

2017-01-01

textabstractAdipose tissue-derived stem cells (ASCs) are known to be able to promote repair of injured tissue via paracrine factors. However, the effect of cell density and inflammatory cytokines on the paracrine ability of ASCs remains largely unknown. To investigate these effects, ASCs were

Beneficial effects of cytokine induced hyperlipidemia.

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Feingold, K R; Hardardóttir, I; Grunfeld, C

1998-01-01

Infection, inflammation and trauma induce marked changes in the plasma levels of a wide variety of proteins (acute phase response), and these changes are mediated by cytokines. The acute phase response is thought to be beneficial to the host. The host's response to injury also results in dramatic alterations in lipid metabolism and circulating lipoprotein levels which are mediated by cytokines. A large number of cytokines including TNF, the interleukins, and the interferons increase serum triglyceride levels. This rapid increase (1-2 h) is predominantly due to an increase in hepatic VLDL secretion while the late increase may be due to a variety of factors including increased hepatic production of VLDL or delayed clearance secondary to a decrease in lipoprotein lipase activity and/or apolipoprotein E levels on VLDL. In animals other than primates, cytokines also increase serum cholesterol levels, most likely by increasing hepatic cholesterol. Cytokines increase hepatic cholesterol synthesis by stimulating HMG CoA reductase gene expression and decrease hepatic cholesterol catabolism by inhibiting cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis. Injury and/or cytokines also decrease HDL cholesterol levels and induce alterations in the composition of HDL. The content of SAA and apolipoprotein J increase, apolipoprotein A1 may decrease, and the cholesterol ester content decreases while free cholesterol increases. Additionally, key proteins involved in HDL metabolism are altered by cytokines; LCAT activity, hepatic lipase activity, and CETP levels decrease. These changes in lipid and lipoprotein metabolism may be beneficial in a number of ways including: lipoproteins competing with viruses for cellular receptors, apolipoproteins neutralizing viruses, lipoproteins binding and targeting parasites for destruction, apolipoproteins lysing parasites, redistribution of nutrients to cells involved in the immune response and/or tissue repair, and

Effect of Cell Seeding Density and Inflammatory Cytokines on Adipose Tissue-Derived Stem Cells : an in Vitro Study

NARCIS (Netherlands)

Sukho, Panithi; Kirpensteijn, Jolle; Hesselink, Jan Willem; van Osch, Gerjo J V M; Verseijden, Femke; Bastiaansen-Jenniskens, Yvonne M

Adipose tissue-derived stem cells (ASCs) are known to be able to promote repair of injured tissue via paracrine factors. However, the effect of cell density and inflammatory cytokines on the paracrine ability of ASCs remains largely unknown. To investigate these effects, ASCs were cultured in 8000

Cytokine balance in human malaria: does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum?

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Raquel M Gonçalves

Full Text Available BACKGROUND: The mechanisms by which humans regulate pro- and anti-inflammatory responses on exposure to different malaria parasites remains unclear. Although Plasmodium vivax usually causes a relatively benign disease, this parasite has been suggested to elicit more host inflammation per parasitized red blood cell than P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS: We measured plasma concentrations of seven cytokines and two soluble tumor necrosis factor (TNF-α receptors, and evaluated clinical and laboratory outcomes, in Brazilians with acute uncomplicated infections with P. vivax (n = 85, P. falciparum (n = 30, or both species (n = 12, and in 45 asymptomatic carriers of low-density P. vivax infection. Symptomatic vivax malaria patients, compared to those infected with P. falciparum or both species, had more intense paroxysms, but they had no clear association with a pro-inflammatory imbalance. To the contrary, these patients had higher levels of the regulatory cytokine interleukin (IL-10, which correlated positively with parasite density, and elevated IL-10/TNF-α, IL-10/interferon (IFN-γ, IL-10/IL-6 and sTNFRII/TNF-α ratios, compared to falciparum or mixed-species malaria patient groups. Vivax malaria patients had the highest levels of circulating soluble TNF-α receptor sTNFRII. Levels of regulatory cytokines returned to normal values 28 days after P. vivax clearance following chemotherapy. Finally, asymptomatic carriers of low P. vivax parasitemias had substantially lower levels of both inflammatory and regulatory cytokines than did patients with clinical malaria due to either species. CONCLUSIONS: Controlling fast-multiplying P. falciparum blood stages requires a strong inflammatory response to prevent fulminant infections, while reducing inflammation-related tissue damage with early regulatory cytokine responses may be a more cost-effective strategy in infections with the less virulent P. vivax parasite. The early induction

Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.

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Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klüter, Harald; Gratchev, Alexei; Harmsen, Martin C; Kzhyshkowska, Julia

2017-10-01

Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications. Copyright © 2016 Elsevier GmbH. All rights reserved.

A Comparitive Assessement of Cytokine Expression in Human-Derived Cell Lines Exposed to Alpha Particles and X-Rays

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Vinita Chauhan

2012-01-01

Full Text Available Alpha- (α- particle radiation exposure has been linked to the development of lung cancer and has been identified as a radiation type likely to be employed in radiological dispersal devices. Currently, there exists a knowledge gap concerning cytokine modulations associated with exposure to α-particles. Bio-plex technology was employed to investigate changes in proinflammatory cytokines in two human-derived cell lines. Cells were irradiated at a dose of 1.5 Gy to either α-particles or X-rays at equivalent dose rates. The two cell lines exhibited a unique pattern of cytokine expression and the response varied with radiation type. Of the 27 cytokines assessed, only vascular endothelin growth factor (VEGF was observed to be modulated in both cell lines solely after α-particle exposure, and the expression of VEGF was shown to be dose responsive. These results suggest that certain proinflammatory cytokines may be involved in the biological effects related to α- particle exposure and the responses are cell type and radiation type specific.

Cytokine Gene Expression in Response to SnSAG1 in Horses with Equine Protozoal Myeloencephalitis

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Spencer, Jennifer A.; Deinnocentes, Patricia; Moyana, Edith M.; Guarino, Anthony J.; Ellison, Siobhan E.; Bird, R. Curtis; Blagburn, Byron L.

2005-01-01

Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome seen in horses from the Americas and is mainly caused by Sarcocystis neurona. Recently, a 29-kDa surface antigen from S. neurona merozoites was identified as being highly immunodominant on a Western blot. This antigen has been sequenced and cloned, and the expressed protein has been named SnSAG1. In a previous study, cell-mediated immune responses to SnSAG1 were shown to be statistically significantly reduced in horses with EPM in comparison to EPM-negative control horses. It therefore appears as though the parasite is able to induce immunosuppression towards parasite-derived antigens as parasite-specific responses are decreased. Isolated peripheral blood lymphocytes from 21 EPM (cerebrospinal fluid [CSF] Western blot)-negative horses with no clinical signs and 21 horses with clinical signs of EPM (CSF Western blot positive) were cocultured with SnSAG1 for 48 and 72 h, and the effect on cytokine production was investigated by means of reverse transcriptase PCR. Cytokines assayed include gamma interferon (IFN-γ), tumor necrosis factor alpha, interleukin (IL)-2, IL-4, and IL-6. β-Actin was used as the housekeeping gene. A Wilcoxon signed-rank test of the findings indicated that there was a statistically significant decrease in IFN-γ production after 48 h in culture for samples from horses with clinical disease. There was also a statistically significant increase in IL-4 production after 72 h in culture for samples from horses with EPM. These results further support the notion that this parasite is able to subvert the immune system in horses with clinical disease. PMID:15879026

Ex Vivo Host and Parasite Response to Antileishmanial Drugs and Immunomodulators

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McMahon-Pratt, Diane; Saravia, Nancy Gore

2015-01-01

Background Therapeutic response in infectious disease involves host as well as microbial determinants. Because the immune and inflammatory response to Leishmania (Viannia) species defines the outcome of infection and efficacy of treatment, immunomodulation is considered a promising therapeutic strategy. However, since Leishmania infection and antileishmanial drugs can themselves modulate drug transport, metabolism and/or immune responses, immunotherapeutic approaches require integrated assessment of host and parasite responses. Methodology To achieve an integrated assessment of current and innovative therapeutic strategies, we determined host and parasite responses to miltefosine and meglumine antimoniate alone and in combination with pentoxifylline or CpG 2006 in peripheral blood mononuclear cells (PBMCs) of cutaneous leishmaniasis patients. Parasite survival and secretion of TNF-α, IFN-γ, IL-10 and IL-13 were evaluated concomitantly in PBMCs infected with Luc-L. (V.) panamensis exposed to meglumine antimoniate (4, 8, 16, 32 and 64 μg SbV/mL) or miltefosine (2, 4, 8, 16 and 32 μM HePC). Concentrations of 4 μM of miltefosine and 8 μg SbV/mL were selected for evaluation in combination with immunomodulators based on the high but partial reduction of parasite burden by these antileishmanial concentrations without affecting cytokine secretion of infected PBMCs. Intracellular parasite survival was determined by luminometry and cytokine secretion measured by ELISA and multiplex assays. Principal Findings Anti- and pro-inflammatory cytokines characteristic of L. (V.) panamensis infection were evaluable concomitantly with viability of Leishmania within monocyte-derived macrophages present in PBMC cultures. Both antileishmanial drugs reduced the parasite load of macrophages; miltefosine also suppressed IL-10 and IL-13 secretion in a dose dependent manner. Pentoxifylline did not affect parasite survival or alter antileishmanial effects of miltefosine or meglumine

Subfractions of enamel matrix derivative differentially influence cytokine secretion from human oral fibroblasts

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Oscar Villa

2015-03-01

Full Text Available 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.

Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

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Alnek, Kristi; Kisand, Kalle; Heilman, Kaire; Peet, Aleksandr; Varik, Karin; Uibo, Raivo

2015-01-01

The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13.

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Gabitass, Rachel F; Annels, Nicola E; Stocken, Deborah D; Pandha, Hardev A; Middleton, Gary W

2011-10-01

We undertook a comprehensive analysis of circulating myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) in pancreatic, esophageal and gastric cancer patients and investigated whether MDSCs are an independent prognostic factor for survival. We evaluated a series of plasma cytokines and in particular re-evaluated the Th2 cytokine interleukin-13 (IL-13). Peripheral blood was collected from 131 cancer patients (46 pancreatic, 60 esophageal and 25 gastric) and 54 healthy controls. PBMC were harvested with subsequent flow cytometric analysis of MDSC (HLADR(-) Lin1(low/-) CD33(+) CD11b(+)) and Treg (CD4(+) CD25(+) CD127(low/-) FoxP3(+)) percentages. Plasma IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 (p70), IL-13, IL-17, G-CSF, IFN-γ, TNF-α and VEGF levels were analyzed by the Bio-Plex cytokine assay. Plasma arginase I levels were analyzed by ELISA. MDSCs and Tregs were statistically significantly elevated in pancreatic, esophageal and gastric cancer compared with controls, and MDSC numbers correlated with Treg levels. Increasing MDSC percentage was associated with increased risk of death, and in a multivariate analysis, MDSC level was an independent prognostic factor for survival. A unit increase in MDSC percentage was associated with a 22% increased risk of death (hazard ratio 1.22, 95% confidence interval 1.06-1.41). Arginase I levels were also statistically significantly elevated in upper gastrointestinal cancer patients compared with controls. There was Th2 skewing for cytokine production in all three diseases, and importantly there were significant elevations of the pivotal Th2 cytokine interleukin-13, an increase that correlated with MDSC levels.

Ecological Factors Determining Abundance of Parasitic Mites on Aedes spp. Larvae

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Nurhadi Eko Firmansyah

2017-12-01

Full Text Available Ability to infestation and abundance of parasitic mites in Aedes spp. larvae cannot be separated from the influence of various factors. Ecological factors have been suggested to play a role determine the presence of parasitic mites that under certain conditions become a key factor in determining the abundance of parasitic mites on Aedes spp. larvae. The aim of this study to determine the ecological factors affect the abundance of parasitic mites on Aedes spp. larvae in Bogor Regency. Capturing of Aedes spp. larvae was performed directly on the habitats found in indoor and outdoor. Capturing mites in the body of Aedes spp. larvae was performed using insect forceps. Ecological factors measured were dissolved oxygen (DO, pH, temperature, and total dissolved solid (TDS. The influence of ecological factors was analyzed using regression and correlation analysis. The result of mite identification has been obtained three species of mites that are Halacarus sp., Histiostoma sp., and Hydrozetes sp. The result indicated that total dissolved solid (TDS and temperature was the factors that determined the abundance of mites. The factors of pH, and dissolved oxygen (DO did not determine the abundance of parasitic mites of Aedes spp. larvae. The research result can be further developed as a new alternative to Dengue Hemorraghic Fever control and provide information on parasitic mites that infest Aedes spp. larvae. In addition, this results become an early step in controlling of Aedes spp. strategy platform by the parasitic mites.

Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

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Kristi Alnek

Full Text Available The production of several cytokines could be dysregulated in type 1 diabetes (T1D. In particular, the activation of T helper (Th type 1 (Th1 cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF and interleukin (IL-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α, Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8, but not human leukocyte antigen (HLA genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

Human astrocytes: secretome profiles of cytokines and chemokines.

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Sung S Choi

Full Text Available Astrocytes play a key role in maintenance of neuronal functions in the central nervous system by producing various cytokines, chemokines, and growth factors, which act as a molecular coordinator of neuron-glia communication. At the site of neuroinflammation, astrocyte-derived cytokines and chemokines play both neuroprotective and neurotoxic roles in brain lesions of human neurological diseases. At present, the comprehensive profile of human astrocyte-derived cytokines and chemokines during inflammation remains to be fully characterized. We investigated the cytokine secretome profile of highly purified human astrocytes by using a protein microarray. Non-stimulated human astrocytes in culture expressed eight cytokines, including G-CSF, GM-CSF, GROα (CXCL1, IL-6, IL-8 (CXCL8, MCP-1 (CCL2, MIF and Serpin E1. Following stimulation with IL-1β and TNF-α, activated astrocytes newly produced IL-1β, IL-1ra, TNF-α, IP-10 (CXCL10, MIP-1α (CCL3 and RANTES (CCL5, in addition to the induction of sICAM-1 and complement component 5. Database search indicated that most of cytokines and chemokines produced by non-stimulated and activated astrocytes are direct targets of the transcription factor NF-kB. These results indicated that cultured human astrocytes express a distinct set of NF-kB-target cytokines and chemokines in resting and activated conditions, suggesting that the NF-kB signaling pathway differentially regulates gene expression of cytokines and chemokines in human astrocytes under physiological and inflammatory conditions.

Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity

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Francesca eCalabrese

2014-12-01

Full Text Available Cytokines are key regulatory mediators involved in the host response to immunological challenges, but also play a critical role in the communication between the immune and the central nervous system. For this, their expression in both systems is under a tight regulatory control. However, pathological conditions may lead to an overproduction of pro-inflammatory cytokines that may have a detrimental impact on central nervous system. In particular, they may damage neuronal structure and function leading to deficits of neuroplasticity, the ability of nervous system to perceive, respond and adapt to external or internal stimuli.In search of the mechanisms by which pro-inflammatory cytokines may affect this crucial brain capability, we will discuss one of the most interesting hypotheses: the involvement of the neurotrophin brain-derived neurotrophic factor, which represents one of the major mediators of neuroplasticity.

Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity.

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Mello, Debora B; Ramos, Isalira P; Mesquita, Fernanda C P; Brasil, Guilherme V; Rocha, Nazareth N; Takiya, Christina M; Lima, Ana Paula C A; Campos de Carvalho, Antonio C; Goldenberg, Regina S; Carvalho, Adriana B

2015-01-01

Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is a complex disease endemic in Central and South America. It has been gathering interest due to increases in non-vectorial forms of transmission, especially in developed countries. The objective of this work was to investigate if adipose tissue-derived mesenchymal stromal cells (ASC) can alter the course of the disease and attenuate pathology in a mouse model of chagasic cardiomyopathy. ASC were injected intraperitoneally at 3 days post-infection (dpi). Tracking by bioluminescence showed that cells remained in the abdominal cavity for up to 9 days after injection and most of them migrated to the abdominal or subcutaneous fat, an early parasite reservoir. ASC injection resulted in a significant reduction in blood parasitemia, which was followed by a decrease in cardiac tissue inflammation, parasitism and fibrosis at 30 dpi. At the same time point, analyses of cytokine release in cells isolated from the heart and exposed to T. cruzi antigens indicated an anti-inflammatory response in ASC-treated animals. In parallel, splenocytes exposed to the same antigens produced a pro-inflammatory response, which is important for the control of parasite replication, in placebo and ASC-treated groups. However, splenocytes from the ASC group released higher levels of IL-10. At 60 dpi, magnetic resonance imaging revealed that right ventricular (RV) dilation was prevented in ASC-treated mice. In conclusion, the injection of ASC early after T. cruzi infection prevents RV remodeling through the modulation of immune responses. Lymphoid organ response to the parasite promoted the control of parasite burden, while the heart, a target organ of Chagas disease, was protected from damage due to an improved control of inflammation in ASC-treated mice.

Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity.

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Debora B Mello

Full Text Available Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi, is a complex disease endemic in Central and South America. It has been gathering interest due to increases in non-vectorial forms of transmission, especially in developed countries. The objective of this work was to investigate if adipose tissue-derived mesenchymal stromal cells (ASC can alter the course of the disease and attenuate pathology in a mouse model of chagasic cardiomyopathy.ASC were injected intraperitoneally at 3 days post-infection (dpi. Tracking by bioluminescence showed that cells remained in the abdominal cavity for up to 9 days after injection and most of them migrated to the abdominal or subcutaneous fat, an early parasite reservoir. ASC injection resulted in a significant reduction in blood parasitemia, which was followed by a decrease in cardiac tissue inflammation, parasitism and fibrosis at 30 dpi. At the same time point, analyses of cytokine release in cells isolated from the heart and exposed to T. cruzi antigens indicated an anti-inflammatory response in ASC-treated animals. In parallel, splenocytes exposed to the same antigens produced a pro-inflammatory response, which is important for the control of parasite replication, in placebo and ASC-treated groups. However, splenocytes from the ASC group released higher levels of IL-10. At 60 dpi, magnetic resonance imaging revealed that right ventricular (RV dilation was prevented in ASC-treated mice.In conclusion, the injection of ASC early after T. cruzi infection prevents RV remodeling through the modulation of immune responses. Lymphoid organ response to the parasite promoted the control of parasite burden, while the heart, a target organ of Chagas disease, was protected from damage due to an improved control of inflammation in ASC-treated mice.

Peripheral parasitaemia and its association with plasma cytokines ...

African Journals Online (AJOL)

Also, plasma levels of cytokines were measured using Th1/Th2 human cytokine ELISA kits (Abcam, UK). Analysis of Variance and Student's t-test were used for Comparison of groups while Pearson's Correlation Coefficient was used for tests of association. Results: The results revealed a mean parasite density of ...

The guanylhydrazone CNI-1493: an inhibitor with dual activity against malaria-inhibition of host cell pro-inflammatory cytokine release and parasitic deoxyhypusine synthase.

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Specht, Sabine; Sarite, Salem Ramadan; Hauber, Ilona; Hauber, Joachim; Görbig, Ulf F; Meier, Chris; Bevec, Dorian; Hoerauf, Achim; Kaiser, Annette

2008-05-01

Malaria is still a major cause of death in the tropics. There is an urgent need for new anti-malarial drugs because drug-resistant plasmodia frequently occur. Over recent years, we elucidated the biosynthesis of hypusine, a novel amino acid contained in eukaryotic initiation factor 5A (eIF-5A) in Plasmodium. Hypusine biosynthesis involves catalysis of deoxyhypusine synthase (DHS) in the first step of post-translational modification. In a screen for new inhibitors of purified plasmodium DHS, CNI-1493, a novel selective pro-inflammatory cytokine inhibitor used in clinical phase II for the treatment of Crohn's disease, inhibited the enzyme of the parasite 3-fold at a concentration of 2 microM. In vitro experiments with 200 microM CNI-1493 in Plasmodium-infected erythrocytes, which lack nuclei and DHS protein, showed a parasite clearance within 2 days. This can presumably be attributed to an anti-proliferating effect because of the inhibition of DHS by the parasite. The determined IC50 of CNI-1493 was 135.79 microM after 72 h. In vivo application of this substance in Plasmodium berghei ANKA-infected C57BL/6 mice significantly reduced parasitemia after dosage of 1 mg/kg or 4 mg/kg/body weight and prevented death of mice with cerebral malaria. This effect was paralleled by a decrease in serum TNF levels of the mice. We suggest that the new mechanism of CNI-1493 is caused by a decrease in modified eIF-5A biosynthesis with a downstream effect on the TNF synthesis of the host. From the current data, we consider CNI-1493 to be a promising drug for anti-malarial therapy because of its combined action, i.e., the decrease in eIF-5A biosynthesis of the parasite and host cell TNF biosynthesis.

Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from LPS-stimulated myeloid cells.

LENUS (Irish Health Repository)

Gleeson, Eimear M

2013-07-19

Vitamin K-dependent proteases generated in response to vascular injury and infection enable fibrin clot formation, but also trigger distinct immuno-regulatory signaling pathways on myeloid cells. Factor Xa, a protease crucial for blood coagulation, also induces protease-activated receptor-dependent cell signaling. Factor Xa can bind both monocytes and macrophages, but whether factor Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production in response to Toll-like receptor activation is not known. In this study, exposure to factor Xa significantly impaired pro-inflammatory cytokine production from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1 monocytic cells and murine macrophages. Furthermore, factor Xa inhibited nuclear factor-kappa B activation in THP-1 reporter cells, requiring phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. Active-site blockade, γ-carboxyglutamic acid domain truncation and a peptide mimic of the factor Xa inter-epidermal growth factor-like region prevented factor Xa inhibition of lipopolysaccharide-induced tumour necrosis factor-α release. In addition, factor Xa anti-inflammatory activity was markedly attenuated by the presence of an antagonist of protease-activated receptor 2, but not protease-activated receptor 1. The key role of protease-activated receptor 2 in eliciting factor Xa-dependent anti-inflammatory signaling on macrophages was further underscored by the inability of factor Xa to mediate inhibition of tumour necrosis factor-α and interleukin-6 release from murine bone marrow-derived protease-activated receptor 2-deficient macrophages. We also show for the first time that, in addition to protease-activated receptor 2, factor Xa requires a receptor-associated protein-sensitive low-density lipoprotein receptor to inhibit lipopolysaccharide-induced cytokine production. Collectively, this study supports a novel function for factor Xa as an endogenous, receptor

Angiogenic Factors and Cytokines in Diabetic Retinopathy

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Abcouwer, Steven F.

2013-01-01

Diabetic retinopathy (DR) is a sight-threatening complication of both type-1 and type-2 diabetes. The recent success of treatments inhibiting the function of vascular endothelial growth factor (VEGF) demonstrates that specific targeting of a growth factor responsible for vascular permeability and growth is an effective means of treating DR-associated vascular dysfunction, edema and angiogenesis. This has stimulated research of alternative therapeutic targets involved in the control of retinal vascular function. However, additional treatment options and preventative measures are still needed and these require a greater understanding of the pathological mechanisms leading to the disturbance of retinal tissue homeostasis in DR. Although severe DR can be treated as a vascular disease, abundant data suggests that inflammation is also occurring in the diabetic retina.Thus, anti-inflammatory therapies may also be useful for treatment and prevention of DR. Herein, the evidence for altered expression of angiogenic factors and cytokines in DR is reviewed and possible mechanisms by which the expression of VEGF and cytokines may be increased in the diabetic retina are examined. In addition, the potential role for microglial activation in diabetic retinal neuroinflammation is explored. PMID:24319628

Neutrophil-Derived Proteases Escalate Inflammation through Activation of IL-36 Family Cytokines

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Conor M. Henry

2016-02-01

Full Text Available Recent evidence has strongly implicated the IL-1 family cytokines IL-36α, IL-36β, and IL-36γ as key initiators of skin inflammation. Similar to the other members of the IL-1 family, IL-36 cytokines are expressed as inactive precursors and require proteolytic processing for activation; however, the responsible proteases are unknown. Here, we show that IL-36α, IL-36β, and IL-36γ are activated differentially by the neutrophil granule-derived proteases cathepsin G, elastase, and proteinase-3, increasing their biological activity ∼500-fold. Active IL-36 promoted a strong pro-inflammatory signature in primary keratinocytes and was sufficient to perturb skin differentiation in a reconstituted 3D human skin model, producing features resembling psoriasis. Furthermore, skin eluates from psoriasis patients displayed significantly elevated cathepsin G-like activity that was sufficient to activate IL-36β. These data identify neutrophil granule proteases as potent IL-36-activating enzymes, adding to our understanding of how neutrophils escalate inflammatory reactions. Inhibition of neutrophil-derived proteases may therefore have therapeutic benefits in psoriasis.

Trichomonas vaginalis exosomes deliver cargo to host cells and mediate host∶parasite interactions.

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Olivia Twu

Full Text Available Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogential tract where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Here, we use a combination of methodologies including cell fractionation, immunofluorescence and electron microscopy, RNA, proteomic and cytokine analyses and cell adherence assays to examine pathogenic properties of T. vaginalis. We have found that T.vaginalis produces and secretes microvesicles with physical and biochemical properties similar to mammalian exosomes. The parasite-derived exosomes are characterized by the presence of RNA and core, conserved exosomal proteins as well as parasite-specific proteins. We demonstrate that T. vaginalis exosomes fuse with and deliver their contents to host cells and modulate host cell immune responses. Moreover, exosomes from highly adherent parasite strains increase the adherence of poorly adherent parasites to vaginal and prostate epithelial cells. In contrast, exosomes from poorly adherent strains had no measurable effect on parasite adherence. Exosomes from parasite strains that preferentially bind prostate cells increased binding of parasites to these cells relative to vaginal cells. In addition to establishing that parasite exosomes act to modulate host∶parasite interactions, these studies are the first to reveal a potential role for exosomes in promoting parasite∶parasite communication and host cell colonization.

Prevalence and Risk Factors of Intestinal Parasites in Cats from China.

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Yang, Yurong; Liang, Hongde

2015-01-01

The prevalence of intestinal parasites in cats from China was largely unknown prior to this study. The aim of the present study was to investigate the presence of intestinal parasites in cats from central China and also identify risk factors for parasitism. Fecal samples from 360 cats were examined using sugar flotation procedure and fecal smear test by microscope. Cats had mixed two or three kinds of parasites infections. Of the 360 cats feces, intestinal parasites positive feces were 149 (41.39%). 64 (17.78%) were infected with Toxocara cati, 61 (16.94%) with Isospora felis, 41 (11.39%) with Isospora rivolta, 33 (9.17%) with Paragonimus, 23 (6.39%) with hookworms, 11 (3.06%) with Toxoplasma-like oocysts, 10 (2.78%) with Trichuris, 4 (1.11%) with lungworm, 2 (0.56%) with Sarcocystis, and 1 (0.28%) with Trematode. The cats' living outdoor was identified as risk factor by statistical analysis. These results provide relevant basic data for assessing the infection of intestinal parasites in cats from central region of China. In conclusion, there was high prevalence of intestinal parasites in cats from China.

Prevalence and Risk Factors of Intestinal Parasites in Cats from China

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Yurong Yang

2015-01-01

Full Text Available The prevalence of intestinal parasites in cats from China was largely unknown prior to this study. The aim of the present study was to investigate the presence of intestinal parasites in cats from central China and also identify risk factors for parasitism. Fecal samples from 360 cats were examined using sugar flotation procedure and fecal smear test by microscope. Cats had mixed two or three kinds of parasites infections. Of the 360 cats feces, intestinal parasites positive feces were 149 (41.39%. 64 (17.78% were infected with Toxocara cati, 61 (16.94% with Isospora felis, 41 (11.39% with Isospora rivolta, 33 (9.17% with Paragonimus, 23 (6.39% with hookworms, 11 (3.06% with Toxoplasma-like oocysts, 10 (2.78% with Trichuris, 4 (1.11% with lungworm, 2 (0.56% with Sarcocystis, and 1 (0.28% with Trematode. The cats’ living outdoor was identified as risk factor by statistical analysis. These results provide relevant basic data for assessing the infection of intestinal parasites in cats from central region of China. In conclusion, there was high prevalence of intestinal parasites in cats from China.

Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii.

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Erica S Martins-Duarte

Full Text Available Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a worldwide disease whose clinical manifestations include encephalitis and congenital malformations in newborns. Previously, we described the synthesis of new ethyl-ester derivatives of the antibiotic ciprofloxacin with ~40-fold increased activity against T. gondii in vitro, compared with the original compound. Cipro derivatives are expected to target the parasite's DNA gyrase complex in the apicoplast. The activity of these compounds in vivo, as well as their mode of action, remained thus far uncharacterized. Here, we examined the activity of the Cipro derivatives in vivo, in a model of acute murine toxoplasmosis. In addition, we investigated the cellular effects T. gondii tachyzoites in vitro, by immunofluorescence and transmission electron microscopy (TEM. When compared with Cipro treatment, 7-day treatments with Cipro derivatives increased mouse survival significantly, with 13-25% of mice surviving for up to 60 days post-infection (vs. complete lethality 10 days post-infection, with Cipro treatment. Light microscopy examination early (6 and 24h post-infection revealed that 6-h treatments with Cipro derivatives inhibited the initial event of parasite cell division inside host cells, in an irreversible manner. By TEM and immunofluorescence, the main cellular effects observed after treatment with Cipro derivatives and Cipro were cell scission inhibition--with the appearance of 'tethered' parasites--malformation of the inner membrane complex, and apicoplast enlargement and missegregation. Interestingly, tethered daughter cells resulting from Cipro derivatives, and also Cipro, treatment did not show MORN1 cap or centrocone localization. The biological activity of Cipro derivatives against C. parvum, an apicomplexan species that lacks the apicoplast, is, approximately, 50 fold lower than that in T. gondii tachyzoites, supporting that these compounds targets the apicoplast. Our results

Factors Associated with Gastrointestinal Parasitic Infections among Young Population in Northeast Brazil

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Juliana Vasconcelos Lyra da Silva

2016-01-01

Full Text Available Background. Intestinal parasitic infections constitute a major public health problem that is frequently associated with poverty, inadequate sanitation, and the nutritional status of the population. Objective. The aim of the present study is to investigate the possible association of parasitic infections, sanitary conditions, hygiene practices, and the nutritional and socioeconomic status of a poor youth population. Methods. A cross-sectional study was conducted with 367 children and adolescents inhabiting a substandard settlement in the urban area of Maceió (Alagoas State, Brazil. Data collection included socioeconomic status, anthropometric measurements, fecal sample examinations, and laboratory blood analysis. The identification of factors associated with gastrointestinal parasitic infections was undertaken through bi- and multivariate analyses. Results. Stool sample analysis obtained from 300 individuals revealed that 204 (68% were infected with at least one parasite species and of these 130 (63.7% were polyparasitized. No significant associations were identified between low height for age (stunted, parasitic infections, and polyparasitism. There was also no association between family income and parasitosis. However, low socioeconomic status proved to be a potential risk factor for parasitic infections. Conclusion. Actions must be taken to improve sanitation, housing, and environmental conditions in order to eliminate the risk factors for parasitic infections, and thereby guarantee a better quality of life for this population.

Stromal cell-derived factor-1 alpha (SDF-1 alpha) improves neural recovery after spinal cord contusion in rats

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Zendedel, A.; Nobakht, M.; Bakhtiyari, M.; Beyer, C.; Kipp, M.; Baazm, M.; Joghataie, M.T.

2012-01-01

Stromal cell-derived factor-1 alpha (SDF-1α) is an important cytokine, implicated in the control of stem cell trafficking and bone marrow-derived stem cell mobilization. Generally, SDF-1α regulates multiple physiological processes such as embryonic development and organ homeostasis. There is also

Withaferin A Associated Differential Regulation of Inflammatory Cytokines

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Seema Dubey

2018-02-01

Full Text Available A role of inflammation-associated cytokines/chemokines has been implicated in a wide variety of human diseases. Here, we investigated the regulation of inflammatory cytokines released by monocyte-derived THP-1 cells following treatment with the dietary agent withaferin A (WFA. Membrane-based cytokine array profiling of the culture supernatant from adenosine triphosphate-stimulated WFA-treated THP-1 cells showed differential regulation of multiple cytokines/chemokines. A selected group of cytokines/chemokines [interleukin-1 beta (IL-1β, CCL2/MCP-1, granulocyte-macrophage colony stimulating factor, PDGF-AA, PTX3, cystatin-3, relaxin-2, TNFRSF8/CD30, and ACRP30] was validated at the transcription level using qPCR. In silico analysis for transcriptional binding factors revealed the presence of nuclear factor-kappa B (NF-κB in a group of downregulated cytokine gene promoters. WFA treatment of THP-1 cells blocks the nuclear translocation of NF-kB and corresponds with the reduced levels of cytokine secretion. To further understand the differential expression of cytokines/chemokines, we showed that WFA alters the nigericin-induced co-localization of NLRP3 and ASC proteins, thereby inhibiting caspase-1 activation, which is responsible for the cleavage and maturation of pro-inflammatory cytokines IL-1β and IL-18. These data suggest that dietary agent WFA concurrently targets NF-κB and the inflammasome complex, leading to inhibition of IL-1β and IL-18, respectively, in addition to differential expression of multiple cytokines/chemokines. Taken together, these results provide a rationale for using WFA to further explore the anti-inflammatory mechanism of cytokines/chemokines associated with inflammatory diseases.

Neutrophil-Derived Proteases Escalate Inflammation through Activation of IL-36 Family Cytokines.

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Henry, Conor M; Sullivan, Graeme P; Clancy, Danielle M; Afonina, Inna S; Kulms, Dagmar; Martin, Seamus J

2016-02-02

Recent evidence has strongly implicated the IL-1 family cytokines IL-36α, IL-36β, and IL-36γ as key initiators of skin inflammation. Similar to the other members of the IL-1 family, IL-36 cytokines are expressed as inactive precursors and require proteolytic processing for activation; however, the responsible proteases are unknown. Here, we show that IL-36α, IL-36β, and IL-36γ are activated differentially by the neutrophil granule-derived proteases cathepsin G, elastase, and proteinase-3, increasing their biological activity ~500-fold. Active IL-36 promoted a strong pro-inflammatory signature in primary keratinocytes and was sufficient to perturb skin differentiation in a reconstituted 3D human skin model, producing features resembling psoriasis. Furthermore, skin eluates from psoriasis patients displayed significantly elevated cathepsin G-like activity that was sufficient to activate IL-36β. These data identify neutrophil granule proteases as potent IL-36-activating enzymes, adding to our understanding of how neutrophils escalate inflammatory reactions. Inhibition of neutrophil-derived proteases may therefore have therapeutic benefits in psoriasis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Three-dimensional structure and cytokine distribution of platelet-rich fibrin.

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Bai, Meng-Yi; Wang, Ching-Wei; Wang, Jyun-Yi; Lin, Ming-Fang; Chan, Wing P

2017-02-01

Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1) can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg); it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5) to low at the plasma end (p=0.19). Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.

Three-dimensional structure and cytokine distribution of platelet-rich fibrin

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Meng-Yi Bai

Full Text Available OBJECTIVES: Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1 can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. METHODS: Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg; it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. RESULTS: Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5 to low at the plasma end (p=0.19. Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. CONCLUSION: Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.

Intestinal parasites in children and soil from Turbaco, Colombia and associated risk factors.

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Villafañe-Ferrer, Lucy M; Pinilla-Pérez, Mavianis

2016-02-01

Objective To determine the frequency of intestinal parasites in children and soil from Turbaco- Colombia and associated risks factors. Methods Analytical study in which 390 children between 2 and 12 years old from 10 neighborhoods of Turbaco were included, whose legal representatives gave informed consent. Three serial samples of feces and 10 soil samples were processed. Risk factors were determined through an interview. Physicochemical and structural characteristics of soils were also evaluated. Results Parasites were found in 30.5 % of children. 162 parasites were observed; the most frequent protozoan was Endolimax nana (30.3 %) and in terms of helminthes, the most frequent was Ascaris lumbricoides (4.9 %). No statistical association between age or sex and intestinal parasites (p>0.05) or between risk factors and intestinal parasites (p>0.05) was found. Low frequencies of intestinal parasites were encountered in soil samples, being more common Entamoeba spp., Giardia spp., and Ascaris lumbricoides. Neighborhoods of Turbaco had sandy dry soil with low content of ions, low conductivity and low organic matter. Conclusion This study showed a low frequency of intestinal parasites in feces and soils. Despite this, pathogenic parasites were found which can affect the health of the population. Besides this, a high percentage of intestinal parasites that are transmitted through feces were detected indicating fecal contamination and low level of hygiene.

T-lymphocyte cytokine mRNA expression in cystic echinococcosis.

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Fauser, S; Kern, P

1997-04-01

In the present study we investigated cytokine mRNA expression by peripheral blood mononuclear cells (PBMC) from patients with cystic echinococcosis (CE) after stimulation with different antigens. By using reverse transcriptase polymerase chain reaction (RT-PCR) we could demonstrate that restimulation with crude Echinococcus granulosus antigen (Eg-Ag) induced or enhanced Th2 cytokine mRNA expression, especially IL-5 (by using antigen from sheep cyst fluid) in 23 out of 26 investigated CE patients and IL-10 (by using antigen from camel cyst fluid) in 10 out of 10 investigated CE patients. In contrast, IL-5 mRNA expression was absent in PBMC of healthy controls after Eg-Ag stimulation. To determine the specificity of this reaction we stimulated PBMC from 11 CE patients with crude Echinococcus multilocularis antigen (Em-Ag) and PBMC from 8 CE patients with Toxocara canis antigen (Tc-Ag). We found that the PBMC of patients showed a similar mRNA cytokine pattern on stimulation with Em-Ag when compared with Eg-Ag stimulation. The cytokine mRNA pattern on stimulation with Tc-Ag, however, resembled the cytokine mRNA pattern of unstimulated PBMC. Furthermore, the stimulation of PBMC with crude Mycobacterium tuberculosis antigen (H37Ra) and purified protein derivative (PPD) of M. tuberculosis revealed distinct IL-5 mRNA expression in all investigated CE patients, whereas in healthy controls IL-5 mRNA expression was very weak or totally absent. Thus, our results indicate an induction of Th2 cytokine mRNA expression in CE patients, which is frequently observed in parasite infections. Interestingly, this response persists after stimulation with tuberculosis antigens, which normally induce Th1 response.

Anti-parasitic action and elimination of intracellular Toxoplasma gondii in the presence of novel thiosemicarbazone and its 4-thiazolidinone derivatives

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C.S. Carvalho

2010-02-01

Full Text Available Toxoplasma, which infects all eukaryotic cells, is considered to be a good system for the study of drug action and of the behavior of infected host cells. In the present study, we asked if thiosemicarbazone derivatives can be effective against tachyzoites and which morphological and ultrastructural features of host cells and parasites are associated with the destruction of Toxoplasma. The compounds were tested in infected Vero cell culture using concentration screens (0.1 to 20 mM. The final concentration of 1 mM was chosen for biological assay. The following results were obtained: 1 These new derivatives decreased T. gondii infection with an in vitro parasite IC50% of 0.2-0.7 mM, without a significant effect on host cells and the more efficient compounds were 2, 3 (thiosemicarbazone derivatives and 4 (thiazolidinone derivative; 2 The main feature observed during parasite elimination was continuous morphological disorganization of the tachyzoite secretory system, progressive organelle vesiculation, and then complete disruption; 3 Ultrastructural assays also revealed that progressive vesiculation in the cytoplasm of treated parasites did not occur in the host cell; 4 Vesiculation inside the parasite resulted in death, but this feature occurred asynchronously in different intracellular tachyzoites; 5 The death and elimination of T. gondii was associated with features such as apoptosis-like stage, acidification and digestion of parasites into parasitophorous vacuoles. Our results suggest that these new chemical compounds are promising for the elimination of intracellular parasites by mainly affecting tachyzoite development at 1 mM concentration for 24 h of treatment.

Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells.

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Regan, Andrew D; Cohen, Rebecca D; Whittaker, Gary R

2009-02-05

Feline infectious peritonitis (FIP) is an invariably fatal disease of cats caused by systemic infection with a feline coronavirus (FCoV) termed feline infectious peritonitis virus (FIPV). The lethal pathology associated with FIP (granulomatous inflammation and T-cell lymphopenia) is thought to be mediated by aberrant modulation of the immune system due to infection of cells such as monocytes and macrophages. Overproduction of pro-inflammatory cytokines occurs in cats with FIP, and has been suggested to play a significant role in the disease process. However, the mechanism underlying this process remains unknown. Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation and pro-inflammatory cytokine production was inhibited by the pyridinyl imidazole inhibitors SB 203580 and SC 409 in a dose-dependent manner. FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors.

Effects of a novel β–lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis

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Danielle Oliveira dos Anjos

2016-12-01

Full Text Available Natural products comprise valuable sources for new antiparasitic drugs. Here we tested the effects of a novel β–lapachone derivative on Trypanosoma cruzi parasite survival and proliferation and used microscopy and cytometry techniques to approach the mechanism(s underlying parasite death. The selectivity index determination indicate that the compound trypanocidal activity was over ten-fold more cytotoxic to epimastigotes than to macrophages or splenocytes. Scanning electron microscopy analysis revealed that the R72 β–lapachone derivative affected the T. cruzi morphology and surface topography. General plasma membrane waving and blebbing particularly on the cytostome region were observed in the R72-treated parasites. Transmission electron microscopy observations confirmed the surface damage at the cytostome opening vicinity. We also observed ultrastructural evidence of the autophagic mechanism termed macroautophagy. Some of the autophagosomes involved large portions of the parasite cytoplasm and their fusion/confluence may lead to necrotic parasite death. The remarkably enhanced frequency of autophagy triggering was confirmed by quantitating monodansylcadaverine labeling. Some cells displayed evidence of chromatin pycnosis and nuclear fragmentation were detected. This latter phenomenon was also indicated by DAPI staining of R72-treated cells. The apoptotis induction was suggested to take place in circa one-third of the parasites assessed by annexin V labeling measured by flow cytometry. TUNEL staining corroborated the apoptosis induction. Propidium iodide labeling indicate that at least 10% of the R72-treated parasites suffered necrosis within 24 h. The present data indicate that the β–lapachone derivative R72 selectively triggers T. cruzi cell death, involving both apoptosis and autophagy-induced necrosis.

Cytokine-like factor-1, a novel soluble protein, shares homology with members of the cytokine type I receptor family.

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Elson, G C; Graber, P; Losberger, C; Herren, S; Gretener, D; Menoud, L N; Wells, T N; Kosco-Vilbois, M H; Gauchat, J F

1998-08-01

In this report we describe the identification, cloning, and expression pattern of human cytokine-like factor 1 (hCLF-1) and the identification and cloning of its murine homologue. They were identified from expressed sequence tags using amino acid sequences from conserved regions of the cytokine type I receptor family. Human CLF-1 and murine CLF-1 shared 96% amino acid identity and significant homology with many cytokine type I receptors. CLF-1 is a secreted protein, suggesting that it is either a soluble subunit within a cytokine receptor complex, like the soluble form of the IL-6R alpha-chain, or a subunit of a multimeric cytokine, e.g., IL-12 p40. The highest levels of hCLF-1 mRNA were observed in lymph node, spleen, thymus, appendix, placenta, stomach, bone marrow, and fetal lung, with constitutive expression of CLF-1 mRNA detected in a human kidney fibroblastic cell line. In fibroblast primary cell cultures, CLF-1 mRNA was up-regulated by TNF-alpha, IL-6, and IFN-gamma. Western blot analysis of recombinant forms of hCLF-1 showed that the protein has the tendency to form covalently linked di- and tetramers. These results suggest that CLF-1 is a novel soluble cytokine receptor subunit or part of a novel cytokine complex, possibly playing a regulatory role in the immune system and during fetal development.

Immunomodulatory effects of the aromatic geranyl derivative filifolinone tested by the induction of cytokine expression.

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Valenzuela, Beatriz; Imarai, Mónica; Torres, René; Modak, Brenda

2013-12-01

Fish farming crops are constantly exposed to infectious diseases due to intensive production conditions under which microorganisms develop and spread easily, resulting in severe economic losses. The massive use of antibiotics to control these diseases has lead to the accumulation of residues and the development of drug resistance. Consequently, it is urgent to develop new pharmacological tools to stimulate protective immune responses in salmonids to combat infectious diseases. We evaluated the immunostimulant activity of terpenoid derivatives isolated from species of the Heliotropium genus, which had previously shown antiviral activity in salmon. The immunomodulatory effects of the 3 H-spiro [1-benzofuran-2,1'-ciclohexane] derivative called filifolinone, were studied in vitro using the SHK-1 cell line derived from leucocytes of salmon head kidney and in vivo in Atlantic salmon. For the evaluation, we studied the effect of this compound in the expression of various cytokines. The results showed that Filifolinone increases the levels of expression of pro-inflammatory and anti-inflammatory cytokines. This suggests that Filifolinone is a potential alternative immunomodulator for veterinary purposes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites.

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Tajebe, Fitsumbrhan; Getahun, Mulusew; Adem, Emebet; Hailu, Asrat; Lemma, Mulualem; Fikre, Helina; Raynes, John; Tamiru, Aschalew; Mulugeta, Zemenay; Diro, Ermias; Toulza, Frederic; Shkedy, Ziv; Ayele, Tadesse; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Takele, Yegnasew; Kropf, Pascale

2017-07-01

Visceral leishmaniasis (VL) is a neglected tropical disease that affects the poorest communities and can cause substantial morbidity and mortality. Visceral leishmaniasis is characterized by the presence of Leishmania parasites in the spleen, liver and bone marrow, hepatosplenomegaly, pancytopenia, prolonged fever, systemic inflammation and low body mass index (BMI). The factors impacting on the severity of VL are poorly characterized. Here we performed a cross-sectional study to assess whether co-infection of VL patients with intestinal parasites influences disease severity, assessed with clinical and haematological data, inflammation, cytokine profiles and BMI. Data from VL patients was similar to VL patients co-infected with intestinal parasites, suggesting that co-infection of VL patients with intestinal parasites does not alter disease severity.

Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites

Science.gov (United States)

Adem, Emebet; Hailu, Asrat; Lemma, Mulualem; Fikre, Helina; Raynes, John; Tamiru, Aschalew; Mulugeta, Zemenay; Diro, Ermias; Toulza, Frederic; Shkedy, Ziv; Ayele, Tadesse; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Takele, Yegnasew

2017-01-01

Visceral leishmaniasis (VL) is a neglected tropical disease that affects the poorest communities and can cause substantial morbidity and mortality. Visceral leishmaniasis is characterized by the presence of Leishmania parasites in the spleen, liver and bone marrow, hepatosplenomegaly, pancytopenia, prolonged fever, systemic inflammation and low body mass index (BMI). The factors impacting on the severity of VL are poorly characterized. Here we performed a cross-sectional study to assess whether co-infection of VL patients with intestinal parasites influences disease severity, assessed with clinical and haematological data, inflammation, cytokine profiles and BMI. Data from VL patients was similar to VL patients co-infected with intestinal parasites, suggesting that co-infection of VL patients with intestinal parasites does not alter disease severity. PMID:28732017

Intestinal Parasitic Infections in Bahir Dar and Risk Factors for Transmission

OpenAIRE

Erko, Berhanu; Medhin, Girmay; Birrie, Hailu

1995-01-01

A study of intestinal parasites and assessment of transmission factors were made in Bahir Dar town, northwestern Ethiopia. Out of 528 children examined by formolether concentration method over 95 % were found to harbour one or more intestinal parasites. Human behaviour and poor sanitary conditions appeared to be responsible for the transmission of geohelminths, faeco-orally transmitted amoebae and water-related schistosome parasites. Health education is suggested to play a vital role in the c...

Evaluation of TNF-α, IL-4, and IL-10 and parasite density in spleen and liver of L. (L.) chagasi naturally infected dogs.

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DE F Michelin, A; Perri, S H V; De Lima, V M F

2011-07-01

Dogs are the main domestic reservoirs of L. (L.) chagasi. Once in the vertebrate host, the parasite can cause visceral leishmaniasis, which can also be transmitted to humans. Cytokines are key elements of the host immune response against Leishmania spp. To investigate whether tumor necrosis factor (TNF)-α, interleukin (IL)-4 and IL-10 are associated with pattern infection in dogs, these cytokines were quantified in the spleen and liver of dogs naturally infected with L. (L.) chagasi, with or without clinical manifestations, and their levels were correlated with the parasite load verified in these organs. A total of 40 adult dogs naturally infected with L. (L.) chagasi were assessed, together with 12 uninfected control dogs. Samples from spleen and liver were used to determine the cytokine levels by capture ELISA and for quantifying parasite load by real-time PCR. Statistical analysis was performed using the minimum Chi square method and group means were compared using the Tukey test. TNF-α, IL-4 and IL-10 levels in infected dogs were higher than in control groups; the liver was the main cytokine-producing organ during infection. The level of splenic TNF-α showed correlation with parasite load and may represent an important marker for infection process evolution, with the participation of IL-10. These results may contribute to a clearer understanding of the immune response in dogs infected with L. (L.) chagasi, which may lead to the development of prophylactic or preventive measures for these animals.

The effect of some ecological factors on the intestinal parasite loads ...

Indian Academy of Sciences (India)

Some ecological factors that might potentially influence intestinal parasite loads in the Asian elephant (Elephas maximus Linn.) were investigated in the Nilgiris, southern India. Fresh dung samples from identified animals were analysed, and the number of eggs/g of dung used as an index of parasite load. Comparisons ...

Southwestern willow flycatchers (Empidonax traillii extimus) in a grazed landscape: factors influencing brood parasitism

Science.gov (United States)

Katherine M. Brodhead; Scott H. Stoleson; Deborah M. Finch

2007-01-01

Brood parasitism by Brown-headed Cowbirds (Molothrus ater; hereafter "cowbirds") is an important factor contributing to the endangered status of the Southwestern Willow Flycatcher (Empidonax traillii extimus, hereafter "flycatcher"). We report on factors that influence brood parasitism on the flycatcher using...

Unique proliferation response in odontoblastic cells derived from human skeletal muscle stem cells by cytokine-induced matrix metalloproteinase-3

International Nuclear Information System (INIS)

Ozeki, Nobuaki; Hase, Naoko; Kawai, Rie; Yamaguchi, Hideyuki; Hiyama, Taiki; Kondo, Ayami; Nakata, Kazuhiko; Mogi, Makio

2015-01-01

A pro-inflammatory cytokine mixture (CM: interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ) and IL-1β-induced matrix metalloproteinase (MMP)-3 activity have been shown to increase the proliferation of rat dental pulp cells and murine stem cell-derived odontoblast-like cells. This suggests that MMP-3 may regulate wound healing and regeneration in the odontoblast-rich dental pulp. Here, we determined whether these results can be extrapolated to human dental pulp by investigating the effects of CM-induced MMP-3 up-regulation on the proliferation and apoptosis of purified odontoblast-like cells derived from human skeletal muscle stem cells. We used siRNA to specifically reduce MMP-3 expression. We found that CM treatment increased MMP-3 mRNA and protein levels as well as MMP-3 activity. Cell proliferation was also markedly increased, with no changes in apoptosis, upon treatment with CM and following the application of exogenous MMP-3. Endogenous tissue inhibitors of metalloproteinases were constitutively expressed during all experiments and unaffected by MMP-3. Although treatment with MMP-3 siRNA suppressed cell proliferation, it also unexpectedly increased apoptosis. This siRNA-mediated increase in apoptosis could be reversed by exogenous MMP-3. These results demonstrate that cytokine-induced MMP-3 activity regulates cell proliferation and suppresses apoptosis in human odontoblast-like cells. - Highlights: • Pro-inflammatory cytokines induce MMP-3 activity in human odontoblast-like cells. • Increased MMP-3 activity can promote cell proliferation in odontoblasts. • Specific loss of MMP-3 increases apoptosis in odontoblasts. • MMP-3 has potential as a promising new target for pupal repair and regeneration

Unique proliferation response in odontoblastic cells derived from human skeletal muscle stem cells by cytokine-induced matrix metalloproteinase-3

Energy Technology Data Exchange (ETDEWEB)

Ozeki, Nobuaki; Hase, Naoko; Kawai, Rie; Yamaguchi, Hideyuki; Hiyama, Taiki [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Aichi (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan); Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Aichi (Japan); Mogi, Makio, E-mail: makio@dpc.agu.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan)

2015-02-01

A pro-inflammatory cytokine mixture (CM: interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ) and IL-1β-induced matrix metalloproteinase (MMP)-3 activity have been shown to increase the proliferation of rat dental pulp cells and murine stem cell-derived odontoblast-like cells. This suggests that MMP-3 may regulate wound healing and regeneration in the odontoblast-rich dental pulp. Here, we determined whether these results can be extrapolated to human dental pulp by investigating the effects of CM-induced MMP-3 up-regulation on the proliferation and apoptosis of purified odontoblast-like cells derived from human skeletal muscle stem cells. We used siRNA to specifically reduce MMP-3 expression. We found that CM treatment increased MMP-3 mRNA and protein levels as well as MMP-3 activity. Cell proliferation was also markedly increased, with no changes in apoptosis, upon treatment with CM and following the application of exogenous MMP-3. Endogenous tissue inhibitors of metalloproteinases were constitutively expressed during all experiments and unaffected by MMP-3. Although treatment with MMP-3 siRNA suppressed cell proliferation, it also unexpectedly increased apoptosis. This siRNA-mediated increase in apoptosis could be reversed by exogenous MMP-3. These results demonstrate that cytokine-induced MMP-3 activity regulates cell proliferation and suppresses apoptosis in human odontoblast-like cells. - Highlights: • Pro-inflammatory cytokines induce MMP-3 activity in human odontoblast-like cells. • Increased MMP-3 activity can promote cell proliferation in odontoblasts. • Specific loss of MMP-3 increases apoptosis in odontoblasts. • MMP-3 has potential as a promising new target for pupal repair and regeneration.

Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis

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Magda Paula Pereira do Nascimento

2011-09-01

Full Text Available Multinucleated giant cells (MGC are cells present in characteristic granulomatous inflammation induced by intracellular infectious agents or foreign materials. The present study evaluated the modulatory effect of granulocyte macrophage colony-stimulating factor (GM-CSF in association with other cytokines such as interferon-gamma (IFN-γ, tumour necrosis factor-alpha, interleukin (IL-10 or transforming growth factor beta (TGF-β1 on the formation of MGC from human peripheral blood monocytes stimulated with Paracoccidioides brasiliensis antigen (PbAg. The generation of MGC was determined by fusion index (FI and the fungicidal activity of these cells was evaluated after 4 h of MGC co-cultured with viable yeast cells of P. brasiliensis strain 18 (Pb18. The results showed that monocytes incubated with PbAg and GM-CSF plus IFN-γ had a significantly higher FI than in all the other cultures, while the addition of IL-10 or TGF-β1 had a suppressive effect on MGC generation. Monocytes incubated with both pro and anti-inflammatory cytokines had a higher induction of foreign body-type MGC rather than Langhans-type MGC. MGC stimulated with PbAg and GM-CSF in association with the other cytokines had increased fungicidal activity and the presence of GM-CSF also partially inhibited the suppressive effects of IL-10 and TGF-β1. Together, these results suggest that GM-CSF is a positive modulator of PbAg-stimulated MGC generation and on the fungicidal activity against Pb18.

Virulent and avirulent strains of equine arteritis virus induce different quantities of TNF-α and other proinflammatory cytokines in alveolar and blood-derived equine macrophages

International Nuclear Information System (INIS)

Moore, Brian D.; Balasuriya, Udeni B.R.; Watson, Johanna L.; Bosio, Catharine M.; MacKay, Robert J.; MacLachlan, N. James

2003-01-01

Equine arteritis virus (EAV) infects endothelial cells (ECs) and macrophages in horses, and many of the clinical manifestations of equine viral arteritis (EVA) reflect vascular injury. To further evaluate the potential role of EAV-induced, macrophage-derived cytokines in the pathogenesis of EVA, we infected cultured equine alveolar macrophages (AMphi), blood monocyte-derived macrophages (BMphi), and pulmonary artery ECs with either a virulent (KY84) or an avirulent (CA95) strain of EAV. EAV infection of equine AMphi, BMphi, and ECs resulted in their activation with increased transcription of genes encoding proinflammatory mediators, including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α. Furthermore, the virulent KY84 strain of EAV induced significantly higher levels of mRNA encoding proinflammatory cytokines in infected AMphi and BMphi than did the avirulent CA95 strain. Treatment of equine ECs with the culture supernatants of EAV-infected AMphi and BMphi also resulted in EC activation with cell surface expression of E-selectin, whereas infection of ECs with purified EAV alone caused only minimal expression of E-selectin. The presence of TNF-α in the culture supernatants of EAV-infected equine AMphi, BMphi, and ECs was confirmed by bioassay, and the virulent KY84 strain of EAV induced significantly more TNF-α in all cell types than did the avirulent CA95 strain. Thus, the data indicate that EAV-induced, macrophage-derived cytokines may contribute to the pathogenesis of EVA in horses, and that the magnitude of the cytokine response of equine AMphi, BMphi, and ECs to EAV infection reflects the virulence of the infecting virus strain

Cytokines, brain-derived neurotrophic factor and C-reactive protein in bipolar I disorder

DEFF Research Database (Denmark)

Jacoby, Anne Sophie; Munkholm, Klaus; Vinberg, Maj

2016-01-01

BACKGROUND: Peripheral blood brain-derived neurotrophic factor (BDNF) and inflammatory markers may reflect key pathophysiological mechanisms in bipolar disorder in relation to disease activity and neuroprogression. AIMS: To investigate whether neutrophins and inflammatory marker vary with mood...... overall compared with healthy control subjects. However, in adjusted models, no statistically significant differences were found in any measure between patients and control individuals. Levels of hsCRP in depressive states were decreased with 40% (95% CI: 5-62%, p=0.029) compared with euthymia and with 48...

Detection of circulating parasite-derived microRNAs in filarial infections.

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Lucienne Tritten

2014-07-01

Full Text Available Filarial nematodes cause chronic and profoundly debilitating diseases in both humans and animals. Applications of novel technology are providing unprecedented opportunities to improve diagnosis and our understanding of the molecular basis for host-parasite interactions. As a first step, we investigated the presence of circulating miRNAs released by filarial nematodes into the host bloodstream. miRNA deep-sequencing combined with bioinformatics revealed over 200 mature miRNA sequences of potential nematode origin in Dirofilaria immitis-infected dog plasma in two independent analyses, and 21 in Onchocerca volvulus-infected human serum. Total RNA obtained from D. immitis-infected dog plasma was subjected to stem-loop RT-qPCR assays targeting two detected miRNA candidates, miR-71 and miR-34. Additionally, Brugia pahangi-infected dog samples were included in the analysis, as these miRNAs were previously detected in extracts prepared from this species. The presence of miR-71 and miR-34 discriminated infected samples (both species from uninfected samples, in which no specific miRNA amplification occurred. However, absolute miRNA copy numbers were not significantly correlated with microfilaraemia for either parasite. This may be due to the imprecision of mf counts to estimate infection intensity or to miRNA contributions from the unknown number of adult worms present. Nonetheless, parasite-derived circulating miRNAs are found in plasma or serum even for those species that do not live in the bloodstream.

Entamoeba lysyl-tRNA synthetase contains a cytokine-like domain with chemokine activity towards human endothelial cells.

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Manuel Castro de Moura

2011-11-01

Full Text Available Immunological pressure encountered by protozoan parasites drives the selection of strategies to modulate or avoid the immune responses of their hosts. Here we show that the parasite Entamoeba histolytica has evolved a chemokine that mimics the sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens endothelial monocyte activating polypeptide II. This Entamoeba EMAPII-like polypeptide (EELP is translated as a domain attached to two different aminoacyl-tRNA synthetases (aaRS that are overexpressed when parasites are exposed to inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human cells, but its cell specificity is different from that of HsEMAPII. We show that cell specificity differences between HsEMAPII and EELP can be swapped by site directed mutagenesis of only two residues in the cytokines' signal sequence. Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human cytokine with modified cell specificity.

Gametocytes of the Malaria Parasite Plasmodium falciparum Interact With and Stimulate Bone Marrow Mesenchymal Cells to Secrete Angiogenetic Factors

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Valeria Messina

2018-03-01

Full Text Available The gametocytes of Plasmodium falciparum, responsible for the transmission of this malaria parasite from humans to mosquitoes, accumulate and mature preferentially in the human bone marrow. In the 10 day long sexual development of P. falciparum, the immature gametocytes reach and localize in the extravascular compartment of this organ, in contact with several bone marrow stroma cell types, prior to traversing the endothelial lining and re-entering in circulation at maturity. To investigate the host parasite interplay underlying this still obscure process, we developed an in vitro tridimensional co-culture system in a Matrigel scaffold with P. falciparum gametocytes and self-assembling spheroids of human bone marrow mesenchymal cells (hBM-MSCs. Here we show that this co-culture system sustains the full maturation of the gametocytes and that the immature, but not the mature, gametocytes adhere to hBM-MSCs via trypsin-sensitive parasite ligands exposed on the erythrocyte surface. Analysis of a time course of gametocytogenesis in the co-culture system revealed that gametocyte maturation is accompanied by the parasite induced stimulation of hBM-MSCs to secrete a panel of 14 cytokines and growth factors, 13 of which have been described to play a role in angiogenesis. Functional in vitro assays on human bone marrow endothelial cells showed that supernatants from the gametocyte mesenchymal cell co-culture system enhance ability of endothelial cells to form vascular tubes. These results altogether suggest that the interplay between immature gametocytes and hBM-MSCs may induce functional and structural alterations in the endothelial lining of the human bone marrow hosting the P. falciparum transmission stages.

Parasitism as the main factor shaping peptide vocabularies in current organisms.

Science.gov (United States)

Zemková, Michaela; Zahradník, Daniel; Mokrejš, Martin; Flegr, Jaroslav

2017-06-01

Self/non-self-discrimination by vertebrate immune systems is based on the recognition of the presence of peptides in proteins of a parasite that are not contained in the proteins of a host. Therefore, a reduction of the number of 'words' in its own peptide vocabulary could be an efficient evolutionary strategy of parasites for escaping recognition. Here, we compared peptide vocabularies of 30 endoparasitic and 17 free-living unicellular organisms and also eight multicellular parasitic and 16 multicellular free-living organisms. We found that both unicellular and multicellular parasites used a significantly lower number of different pentapeptides than free-living controls. Impoverished pentapeptide vocabularies in parasites were observed across all five clades that contain both the parasitic and free-living species. The effect of parasitism on a number of peptides used in an organism's proteins is larger than effects of all other studied factors, including the size of a proteome, the number of encoded proteins, etc. This decrease of pentapeptide diversity was partly compensated for by an increased number of hexapeptides. Our results support the hypothesis of parasitism-associated reduction of peptide vocabulary and suggest that T-cell receptors mostly recognize the five amino acids-long part of peptides that are presented in the groove of major histocompatibility complex molecules.

Plant Hormone Salicylic Acid Produced by a Malaria Parasite Controls Host Immunity and Cerebral Malaria Outcome.

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Ryuma Matsubara

Full Text Available The apicomplexan parasite Toxoplasma gondii produces the plant hormone abscisic acid, but it is unclear if phytohormones are produced by the malaria parasite Plasmodium spp., the most important parasite of this phylum. Here, we report detection of salicylic acid, an immune-related phytohormone of land plants, in P. berghei ANKA and T. gondii cell lysates. However, addition of salicylic acid to P. falciparum and T. gondii culture had no effect. We transfected P. falciparum 3D7 with the nahG gene, which encodes a salicylic acid-degrading enzyme isolated from plant-infecting Pseudomonas sp., and established a salicylic acid-deficient mutant. The mutant had a significantly decreased concentration of parasite-synthesized prostaglandin E2, which potentially modulates host immunity as an adaptive evolution of Plasmodium spp. To investigate the function of salicylic acid and prostaglandin E2 on host immunity, we established P. berghei ANKA mutants expressing nahG. C57BL/6 mice infected with nahG transfectants developed enhanced cerebral malaria, as assessed by Evans blue leakage and brain histological observation. The nahG-transfectant also significantly increased the mortality rate of mice. Prostaglandin E2 reduced the brain symptoms by induction of T helper-2 cytokines. As expected, T helper-1 cytokines including interferon-γ and interleukin-2 were significantly elevated by infection with the nahG transfectant. Thus, salicylic acid of Plasmodium spp. may be a new pathogenic factor of this threatening parasite and may modulate immune function via parasite-produced prostaglandin E2.

The levels of 12 cytokines and growth factors in tears: hyperthyreosis vs euthyreosis.

Science.gov (United States)

Mandić, Jelena Juri; Kozmar, Ana; Kusačić-Kuna, Sanja; Jazbec, Anamarija; Mandić, Krešimir; Mrazovac, Danijela; Vukojević, Nenad

2018-04-01

Simultaneous analyses of the contents and ratios of 12 cytokines and growth factors in single samples of human tears were performed, and the results were compared between a group of healthy subjects and a group of patients with Graves' hyperthyreosis (GH) without thyroid-associated orbitopathy (TAO). Determinations and concentration measurements of interleukins (IL-2, IL4, IL-6, IL-8, IL-10, IL-1α, and IL-1β) interferon (IFN-γ), tumor necrosis factor (TNF-α), monocyte chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were performed with single tear samples from 21 patients with hyperthyreosis and 22 healthy subjects. The analyses were performed using a Randox microchip with an Evidence Biochip Array Analyzer. We found significant differences between the healthy donor group and the hyperthyreosis group in the levels of IL-6, IL-10, VEGF, IL-1α, and MCP-1. The concentration of IL-6 was considerably higher in the hyperthyreosis group, IL-10 was higher in the healthy donor group, and VEGF and MPC-1 were higher in the hyperthyreosis group. The IL-8 and IFN-γ levels were higher in the hyperthyreosis group. The ratios of all of the cytokines to anti-inflammatory IL-10 were significantly elevated in the hyperthyreosis group. There are clear differences in the levels of cytokines and growth factors in the tears of healthy subjects and patients with GH without TAO. Tear cytokine changes and related dysfunctional tear syndrome (DTS) could be an early sign of occult TAO in Graves' hyperthyreosis patients.

Functional Impairment of Myeloid Dendritic Cells during Advanced Stage of HIV-1 Infection: Role of Factors Regulating Cytokine Signaling.

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Meenakshi Sachdeva

Full Text Available Severely immunocompromised state during advanced stage of HIV-1 infection has been linked to functionally defective antigen presentation by dendritic cells (DCs. The molecular mechanisms behind DC impairment are still obscure. We investigated changes in DC function and association of key regulators of cytokine signaling during different stages of HIV-1 infection and following antiretroviral therapy (ART.Phenotypic and functional characteristics of circulating myeloid DCs (mDCs in 56 ART-naive patients (23 in early and 33 in advanced stage of disease, 36 on ART and 24 healthy controls were evaluated. Sixteen patients were studied longitudinally prior-to and 6 months after the start of ART. For functional studies, monocyte-derived DCs (Mo-DCs were evaluated for endocytosis, allo-stimulation and cytokine secretion. The expression of suppressor of cytokine signaling (SOCS-1 and other regulators of cytokine signaling was evaluated by real-time RT-PCR.The ability to respond to an antigenic stimulation was severely impaired in patients in advanced HIV-1 disease which showed partial recovery in the treated group. Mo-DCs from patients with advanced HIV-disease remained immature with low allo-stimulation and reduced cytokine secretion even after TLR-4 mediated stimulation ex-vivo. The cells had an increased expression of negative regulatory factors like SOCS-1, SOCS-3, SH2-containing phosphatase (SHP-1 and a reduced expression of positive regulators like Janus kinase (JAK2 and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB1. A functional recovery after siRNA mediated silencing of SOCS-1 in these mo-DCs confirms the role of negative regulatory factors in functional impairment of these cells.Functionally defective DCs in advanced stage of HIV-1 infection seems to be due to imbalanced state of negative and positive regulatory gene expression. Whether this is a cause or effect of increased viral replication at this stage of disease

Emerging Functions of Transcription Factors in Malaria Parasite

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Renu Tuteja

2011-01-01

Full Text Available Transcription is a process by which the genetic information stored in DNA is converted into mRNA by enzymes known as RNA polymerase. Bacteria use only one RNA polymerase to transcribe all of its genes while eukaryotes contain three RNA polymerases to transcribe the variety of eukaryotic genes. RNA polymerase also requires other factors/proteins to produce the transcript. These factors generally termed as transcription factors (TFs are either associated directly with RNA polymerase or add in building the actual transcription apparatus. TFs are the most common tools that our cells use to control gene expression. Plasmodium falciparum is responsible for causing the most lethal form of malaria in humans. It shows most of its characteristics common to eukaryotic transcription but it is assumed that mechanisms of transcriptional control in P. falciparum somehow differ from those of other eukaryotes. In this article we describe the studies on the main TFs such as myb protein, high mobility group protein and ApiA2 family proteins from malaria parasite. These studies show that these TFs are slowly emerging to have defined roles in the regulation of gene expression in the parasite.

Comparison of Different Cytokine Conditions Reveals Resveratrol as a New Molecule for Ex Vivo Cultivation of Cord Blood-Derived Hematopoietic Stem Cells.

Science.gov (United States)

Heinz, Niels; Ehrnström, Birgitta; Schambach, Axel; Schwarzer, Adrian; Modlich, Ute; Schiedlmeier, Bernhard

2015-09-01

Human cord blood (CB)-derived hematopoietic stem cells (HSCs) are an interesting source for HSC transplantation. However, the number of collected CB-HSCs is often too low for one transplantation; therefore, ex vivo expansion of CB-HSCs is desirable. Current expansion protocols are based on the use of cytokine combinations, including insulin-like growth factor-binding protein 2 (IGFBP2) and angiopoietin-like proteins, or combinations with "small molecules" such as stemregenin-1. The aim of our project was to compare the potential of different CB-HSC expansion strategies side-by-side by phenotypical analysis in vitro and serial engraftment properties in NOD/SCID/IL2rg-/- (NSG) immunodeficient mice. We further identified resveratrol, a naturally occurring polyphenol, as a new, alternative small molecule combined with cytokines to facilitate serum-free ex vivo expansion of human CB-HSCs. The cultivation in resveratrol preserved the CB-HSC phenotype in vitro most efficiently and was ∼2 times more potent than commonly used cytokine conditions (including stem cell factor, thrombopoietin, Fms-related tyrosine kinase 3 ligand, interleukin-6) and the recently established serum-free culture, including IGFBP2 and angiopoietin-like 5. Serial transplantation studies further confirmed resveratrol to support robust multilineage engraftment in primary and secondary NSG recipients. Therefore, our work proposes resveratrol as a new small molecule for improved ex vivo culture and modification of human HSCs based on an efficient ex vivo propagation of the HSC fate. Human cord blood (CB)-derived hematopoietic stem cells (HSCs) are an important source for HSC transplantations but restricted in their usage because of their low numbers. In gene therapy, modifications of HSCs relies on their ex vivo modification without losing their stemness properties. Therefore, ex vivo cultivation and expansion of CB-HSCs is important for their effective application in HSC transplantation and gene

Cytokines and Growth Factors Expressed by Human Cutaneous Melanoma

Energy Technology Data Exchange (ETDEWEB)

Elias, Elias G., E-mail: george.elias@medstar.net; Hasskamp, Joanne H.; Sharma, Bhuvnesh K. [Maryland Melanoma Center, Weinberg Cancer Institute, Franklin Square Hospital Center, Baltimore, MD (United States)

2010-05-07

Cytokines and growth factors have biologic effects that could stimulate tumor growth, invasion and angiogenesis. The incidence of 24 factors was investigated in 25 cultured human melanoma cell lines and in 62 fixed tissues at different stages of the disease. Over 80% of the human melanoma cell lines expressed TGF-β, IL-8, IL-6, VEGF, PDGF-AA and OPN. Significantly higher TGF-β, IGF-1 and IL-15 were determined in primary lesions compared to distant metastases by immunohistochemistry. Illustrating the complexity of the milieu of the tumor microenvironment, some of these factors may have to be considered in targeted therapy.

Cytokine modulation by glucocorticoids: mechanisms and actions in cellular studies.

Science.gov (United States)

Brattsand, R; Linden, M

1996-01-01

Glucocorticoids inhibit the expression and action of most cytokines. This is part of the in vivo feed-back system between inflammation-derived cytokines and CNS-adrenal produced corticosteroids with the probable physiological relevance to balance parts of the host defence and anti-inflammatory systems of the body. Glucocorticoids modulate cytokine expression by a combination of genomic mechanisms. The activated glucocorticoid-receptor complex can (i) bind to and inactivate key proinflammatory transcription factors (e.g. AP-1, NF kappa B). This takes place at the promotor responsive elements of these factors, but has also been reported without the presence of DNA; (ii) via glucocorticoid responsive elements (GRE), upregulate the expression of cytokine inhibitory proteins, e.g. I kappa B, which inactivates the transcription factor NF kappa B and thereby the secondary expression of a series of cytokines; (iii) reduce the half-life time and utility of cytokine mRNAs. In studies with triggered human blood mononuclear cells in culture, glucocorticoids strongly diminish the production of the 'initial phase' cytokines IL-1 beta and TNF-alpha and the 'immunomodulatory' cytokines IL-2, IL-3, IL-4, IL-5, IL-10, IL-12 and IFN-gamma, as well as of IL-6, IL-8 and the growth factor GM-CSF. While steroid treatment broadly attenuates cytokine production, it cannot modulate it selectively, e.g. just the TH0, the TH1 or the TH2 pathways. The production of the 'anti-inflammatory' IL-10 is also inhibited. The exceptions of steroid down-regulatory activity on cytokine expression seem to affect 'repair phase' cytokines like TGF-beta and PDGF. These are even reported to be upregulated, which may explain the rather weak steroid dampening action on healing and fibrotic processes. Some growth factors, e.g. G-CSF and M-CSF, are only weakly affected. In addition to diminishing the production of a cytokine, steroids can also often inhibit its subsequent actions. Because cytokines work in

PERIPHERAL PARASITAEMIA AND ITS ASSOCIATION WITH PLASMA CYTOKINES LEVELS IN MALARIA-INFECTED PREGNANT WOMEN IN ABA, ABIA STATE, NIGERIA.

Science.gov (United States)

Ifeanyichukwu, M O; Okamgba, O C; Amilo, G I; Nwokorie, E A

2017-01-01

Cytokines in pregnant female may not be a normal phenomenon as malarial infection is often associated with strong CD4+ cell activation and up-regulation of pro-inflammatory cytokines. We investigated the relationship between peripheral parasitaemia and plasma levels of cytokines among malaria infected pregnant women in Aba, Abia State, Nigeria. A total of 206 non-HIV positive asymptomatic malaria parasitaemic (n=144) and non-parasitaemic (n=62) pregnant women were recruited for this study alongside 80 non-pregnant women who served as positive (n=40) and negative (n=40) controls. Blood samples were aseptically collected from each subject and tested for HIV and malaria parasites using standard methods. Also, plasma levels of cytokines were measured using Th1/Th2 human cytokine ELISA kits (Abcam, UK). Analysis of Variance and Student's t-test were used for Comparison of groups while Pearson's Correlation Coefficient was used for tests of association. The results revealed a mean parasite density of 685.56±484.55 parasites/µl of blood. Malaria infected pregnant subjects showed significantly higher levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-10 when compared with their non-infected counterparts (P< 0.05). The cytokines evaluated were higher in moderate parasitaemia than mild parasitaemia. Positive correlation existed between peripheral parasite density (PPD) and IL-4 (r= 0.24, P=0.004), PPD and IL-6 (r = 0.35, P = 0.001) as well as PPD and IL-10 (r = 0.29, P = 0.001). This study showed that increase in peripheral parasitaemia increased levels of some plasma cytokines (IL-4, IL-6 and IL-10) but not IFN-γ and TNF-α in the malaria infected pregnant women studied.

Cytokines, chemokines, and colony-stimulating factors in human milk: the 1997 update.

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Garofalo, R P; Goldman, A S

1998-01-01

Epidemiologic studies conducted over the past 30 years to investigate the protective functions of human milk strongly support the notion that breast-feeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult due to its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. Nevertheless, a host of bioactive substances including hormones, growth factors, and immunological factors such as cytokines have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of the immune system. Several different cytokines and chemokines have been discovered in human milk over the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system.

The cellular prion protein negatively regulates phagocytosis and cytokine expression in murine bone marrow-derived macrophages.

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Min Wang

Full Text Available The cellular prion protein (PrP(C is a glycosylphosphatidylinositol (GPI-anchored glycoprotein on the cell surface. Previous studies have demonstrated contradictory roles for PrP(C in connection with the phagocytic ability of macrophages. In the present work, we investigated the function of PrP(C in phagocytosis and cytokine expression in bone marrow-derived macrophages infected with Escherichia coli. E. coli infection induced an increase in the PRNP mRNA level. Knockout of PrP(C promoted bacterial uptake; upregulated Rab5, Rab7, and Eea1 mRNA expression; and increased the recruitment of lysosomal-associated membrane protein-2 to phagosomes, suggesting enhanced microbicidal activity. Remarkably, knockout of PrP(C suppressed the proliferation of internalized bacteria and increased the expression of cytokines such as interleukin-1β. Collectively, our data reveal an important role of PrP(C as a negative regulator for phagocytosis, phagosome maturation, cytokine expression, and macrophage microbicidal activity.

Food plant derived disease tolerance and resistance in a natural butterfly-plant-parasite interactions.

Science.gov (United States)

Sternberg, Eleanore D; Lefèvre, Thierry; Li, James; de Castillejo, Carlos Lopez Fernandez; Li, Hui; Hunter, Mark D; de Roode, Jacobus C

2012-11-01

Organisms can protect themselves against parasite-induced fitness costs through resistance or tolerance. Resistance includes mechanisms that prevent infection or limit parasite growth while tolerance alleviates the fitness costs from parasitism without limiting infection. Although tolerance and resistance affect host-parasite coevolution in fundamentally different ways, tolerance has often been ignored in animal-parasite systems. Where it has been studied, tolerance has been assumed to be a genetic mechanism, unaffected by the host environment. Here we studied the effects of host ecology on tolerance and resistance to infection by rearing monarch butterflies on 12 different species of milkweed food plants and infecting them with a naturally occurring protozoan parasite. Our results show that monarch butterflies experience different levels of tolerance to parasitism depending on the species of milkweed that they feed on, with some species providing over twofold greater tolerance than other milkweed species. Resistance was also affected by milkweed species, but there was no relationship between milkweed-conferred resistance and tolerance. Chemical analysis suggests that infected monarchs obtain highest fitness when reared on milkweeds with an intermediate concentration, diversity, and polarity of toxic secondary plant chemicals known as cardenolides. Our results demonstrate that environmental factors-such as interacting species in ecological food webs-are important drivers of disease tolerance. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Modulation of PBMC-decay accelerating factor (PBMC-DAF) and cytokines in rheumatoid arthritis.

Science.gov (United States)

Pahwa, Roma; Kumar, Uma; Das, Nibhriti

2016-03-01

Studies have suggested that abnormal expression of complement regulatory proteins and cytokines contribute significantly to the path-physiology of rheumatoid arthritis. In this context, Decay accelerating factor (DAF) a complement regulatory protein is gaining increased attention. With the notion that immune effecter mechanisms are all interlinked and circulating peripheral blood mononuclear cells (PBMCs) should have a role in a systemic disease like rheumatoid arthritis, we studied the modulation and significance of PBMC-DAF and cytokines in RA. Seventy-five RA patients and 75 healthy controls were recruited. Expression of DAF and cytokines (IFN-γ, IL-17A and IL-10) in the PBMCs of patients and controls was determined. Correlations among DAF, cytokines, and disease activity were evaluated by standard statistical methods. The effect of IFN-γ, IL-17A, and IL-10 on the expression of DAF in patients and controls was studied in vitro. Expression of PBMC-DAF declined in patients both at mRNA and surface level and correlated negatively with the disease activity. Expression of IFN-γ also declined in patients but correlated positively with DAF and negatively with disease activity. Expression of IL-17A and IL-10 was higher in patients. The levels correlated positively with disease activity and negatively with DAF both in patients and controls. In vitro studies indicated that IFN-γ up-regulated DAF expression in PBMCs, whereas IL-17A and IL-10 had negative effect on the same. The decline in the PBMC-DAF is a contributing factor in manifestations of RA. Cytokine environment contributes to this decline. These findings brought novel insights into the complement-cytokine axis in the path-physiology of RA.

Novel application of stem cell-derived factors for periodontal regeneration

International Nuclear Information System (INIS)

Inukai, Takeharu; Katagiri, Wataru; Yoshimi, Ryoko; Osugi, Masashi; Kawai, Takamasa; Hibi, Hideharu; Ueda, Minoru

2013-01-01

Highlights: ► Mesenchymal stem cells (MSCs) secrete a variety of cytokines. ► Cytokines were detected in conditioned medium from cultured MSCs (MSC-CM). ► MSC-CM enhanced activation of dog MSCs and periodontal ligament cells. ► MSC-CM significantly promoted alveolar bone and cementum regeneration. ► Multiple cytokines contained in MSC-CM promote periodontal regeneration. -- Abstract: The effect of conditioned medium from cultured mesenchymal stem cells (MSC-CM) on periodontal regeneration was evaluated. In vitro, MSC-CM stimulated migration and proliferation of dog MSCs (dMSCs) and dog periodontal ligament cells (dPDLCs). Cytokines such as insulin-like growth factor, vascular endothelial growth factor, transforming growth factor-β1, and hepatocyte growth factor were detected in MSC-CM. In vivo, one-wall critical-size, intrabony periodontal defects were surgically created in the mandible of dogs. Dogs with these defects were divided into three groups that received MSC-CM, PBS, or no implants. Absorbable atelo-collagen sponges (TERUPLUG®) were used as a scaffold material. Based on radiographic and histological observation 4 weeks after transplantation, the defect sites in the MSC-CM group displayed significantly greater alveolar bone and cementum regeneration than the other groups. These findings suggest that MSC-CM enhanced periodontal regeneration due to multiple cytokines contained in MSC-CM.

Cytokines and Growth Factors Expressed by Human Cutaneous Melanoma

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Elias G. Elias

2010-05-01

Full Text Available Cytokines and growth factors have biologic effects that could stimulate tumor growth, invasion and angiogenesis. The incidence of 24 factors was investigated in 25 cultured human melanoma cell lines and in 62 fixed tissues at different stages of the disease. Over 80% of the human melanoma cell lines expressed TGF-β, IL-8, IL-6, VEGF, PDGF-AA and OPN. Significantly higher TGF-β, IGF-1 and IL-15 were determined in primary lesions compared to distant metastases by immunohistochemistry. Illustrating the complexity of the milieu of the tumor microenvironment, some of these factors may have to be considered in targeted therapy.

Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids.

Science.gov (United States)

Das, Undurti N

2013-10-01

Autism has a strong genetic and environmental basis in which inflammatory markers and factors concerned with synapse formation, nerve transmission, and information processing such as brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs): arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) and their products and neurotransmitters: dopamine, serotonin, acetylcholine, γ-aminobutyric acid, and catecholamines and cytokines are altered. Antioxidants, vitamins, minerals, and trace elements are needed for the normal metabolism of neurotrophic factors, eicosanoids, and neurotransmitters, supporting reports of their alterations in autism. But, the exact relationship among these factors and their interaction with genes and proteins concerned with brain development and growth is not clear. It is suggested that maternal infections and inflammation and adverse events during intrauterine growth of the fetus could lead to alterations in the gene expression profile and proteomics that results in dysfunction of the neuronal function and neurotransmitters, alteration(s) in the metabolism of PUFAs and their metabolites resulting in excess production of proinflammatory eicosanoids and cytokines and a deficiency of anti-inflammatory cytokines and bioactive lipids that ultimately results in the development of autism. Based on these evidences, it is proposed that selective delivery of BDNF and methods designed to augment the production of anti-inflammatory cytokines and eicosanoids and PUFAs may prevent, arrest, or reverse the autism disease process. Copyright © 2013 Elsevier Inc. All rights reserved.

Key cytokines of adaptive immunity are differentially induced in rainbow trout kidney by a group of structurally related geranyl aromatic derivatives.

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Valenzuela, Beatriz; Obreque, Javiera; Soto-Aguilera, Sarita; Maisey, Kevin; Imarai, Mónica; Modak, Brenda

2016-02-01

Filifolinone is a semi-synthetic terpenoid derivative obtained from Heliotropium filifolium that increases the expression level of pro-inflammatory and anti-inflammatory cytokines in kidney cells of salmon. Because cytokines are produced in response to a foreign organism and by distinct other signals modulating immune responses, we further studied the potential immunomodulatory effects of a group of structural related terpenoid derivatives from H. filifolium on salmonids to determine the relationship between the chemical structure of the derivatives and their ability to modify cytokine expression and the lymphoid content. The resin and four 3H-spiro 1-benzofuran-2,1'-cyclohexane derivatives were tested in vivo in rainbow trout (Oncorhynchus mykiss) by quantifying the transcript levels of antiviral and T helper-type cytokines and T and B cells in the kidney. Three of the four terpenoids differ only in the C-7'substituent of the cyclohexane and the presence of the ketone group at this position in Filifolinone appeared responsible of an important up-regulation of IFN-α1, IFN-γ, IL-4/13A and IL-17D in the kidney of the treated trout. In addition, the absence of a methoxy group in carbon 7 of the benzene ring, found in all compounds but not in Folifolinoic acid, produced a significant reduction of IFN-γ, IL-12 and IL-4/13A transcripts. B cells were not affected by the compound treatment but Filifolinoic acid and the resin induced a significant reduction of T cells. Altogether, results showed that immunomodulating responses observed in the trout by effect of 3H-spiro 1-benzofuran-2,1'-cyclohexane derivatives is related to the presence of the ketone group in the carbon 7' and the methoxy group in carbon 7 of the benzene ring, being Filifolinone the most active immunostimulatory compound identified. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ant parasite queens revert to mating singly

DEFF Research Database (Denmark)

Sumner, Seirian; Hughes, William Owen Hamar; Pedersen, Jes Søe

2004-01-01

quantified and they tend to be similar in related species. Here we compare the mating strategies of the leaf-cutting ant Acromyrmex echinatior and its recently derived social parasite Acromyrmex insinuator, which is also its closest relative 2 (see Fig. 1 ). We find that although the host queens mate with up......A parasitic ant has abandoned the multiple mating habit of the queens of its related host. Multiple mating (polyandry) is widespread among animal groups, particularly insects 1 . But the factors that maintain it and underlie its evolution are hard to verify because benefits and costs are not easily...... to a dozen different males, the social parasite mates only singly. This rapid and surprising reversion to single mating in a socially parasitic ant indicates that the costs of polyandry are probably specific to a free-living lifestyle....

Long-term cytokine and growth factor release from equine platelet-rich fibrin clots obtained with two different centrifugation protocols.

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Jiménez-Aristizabal, Román F; López, Catalina; Álvarez, María E; Giraldo, Carlos; Prades, Marta; Carmona, Jorge U

2017-09-01

To compare the temporal release (over three weeks) of tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-1 receptor antagonist (IL-1ra), platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta-1 (TGF-β 1 ) from two platelet-rich fibrin (PRF) preparations from equine blood obtained at either 240g/8min or 416g/10min. Whole blood from 10 horses was used to obtain PRF clots by two different centrifugation protocols. After 1h of rest, PRF clots were deposited in wells with culture medium, which was changed at 6h, 24h and then every 48h to 21days. Cytokines and GFs were measured by ELISA at 1h (serum supernatants from PRF clots) and all time points of culture medium change. A negative control (plasma) and a positive control (blood lysate) were also included. There were no relevant differences between the two protocols for the temporal release of proteins. However, a significant (p=0.01) effect of time was noted. All cytokines were detected after 6h of PRF clot culture until day 21. GF were detected at 1h until day 21. The concentrations for these proteins diminished gradually over time. A highly significant (p=0.01) correlation was noticed between all the proteins evaluated. Leukocytes enmeshed in PRF clots were able to produce cytokines, TGF-β 1 and PDGF-BB. These findings demonstrate a paramount role of leukocytes in wound healing induced or modified by PRF clots in mammals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytokines and Liver Diseases

Directory of Open Access Journals (Sweden)

Herbert Tilg

2001-01-01

Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

Parasitism can be a confounding factor in assessing the response of zebra mussels to water contamination.

Science.gov (United States)

Minguez, Laëtitia; Buronfosse, Thierry; Beisel, Jean-Nicolas; Giambérini, Laure

2012-03-01

Biological responses measured in aquatic organisms to monitor environmental pollution could be also affected by different biotic and abiotic factors. Among these environmental factors, parasitism has often been neglected even if infection by parasites is very frequent. In the present field investigation, the parasite infra-communities and zebra mussel biological responses were studied up- and downstream a waste water treatment plant in northeast France. In both sites, mussels were infected by ciliates and/or intracellular bacteria, but prevalence rates and infection intensities were different according to the habitat. Concerning the biological responses differences were observed related to the site quality and the infection status. Parasitism affects both systems but seemed to depend mainly on environmental conditions. The influence of parasites is not constant, but remains important to consider it as a potential confounding factor in ecotoxicological studies. This study also emphasizes the interesting use of integrative indexes to synthesize data set. Copyright © 2011 Elsevier Ltd. All rights reserved.

Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children

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Sijuade Abayomi

2010-02-01

Full Text Available Abstract Background Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. Methods The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. Results 1,237 of 2,752 children (45% had delay in parasite clearance. Overall 211 children (17% with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P 50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P 20000/μl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P Conclusion Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa.

Novel application of stem cell-derived factors for periodontal regeneration

Energy Technology Data Exchange (ETDEWEB)

Inukai, Takeharu, E-mail: t-inukai@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Katagiri, Wataru, E-mail: w-kat@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Yoshimi, Ryoko, E-mail: lianzi@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Osugi, Masashi, E-mail: masashi@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Kawai, Takamasa, E-mail: takamasa@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Hibi, Hideharu, E-mail: hibihi@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Ueda, Minoru, E-mail: mueda@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan)

2013-01-11

Highlights: Black-Right-Pointing-Pointer Mesenchymal stem cells (MSCs) secrete a variety of cytokines. Black-Right-Pointing-Pointer Cytokines were detected in conditioned medium from cultured MSCs (MSC-CM). Black-Right-Pointing-Pointer MSC-CM enhanced activation of dog MSCs and periodontal ligament cells. Black-Right-Pointing-Pointer MSC-CM significantly promoted alveolar bone and cementum regeneration. Black-Right-Pointing-Pointer Multiple cytokines contained in MSC-CM promote periodontal regeneration. -- Abstract: The effect of conditioned medium from cultured mesenchymal stem cells (MSC-CM) on periodontal regeneration was evaluated. In vitro, MSC-CM stimulated migration and proliferation of dog MSCs (dMSCs) and dog periodontal ligament cells (dPDLCs). Cytokines such as insulin-like growth factor, vascular endothelial growth factor, transforming growth factor-{beta}1, and hepatocyte growth factor were detected in MSC-CM. In vivo, one-wall critical-size, intrabony periodontal defects were surgically created in the mandible of dogs. Dogs with these defects were divided into three groups that received MSC-CM, PBS, or no implants. Absorbable atelo-collagen sponges (TERUPLUG Registered-Sign ) were used as a scaffold material. Based on radiographic and histological observation 4 weeks after transplantation, the defect sites in the MSC-CM group displayed significantly greater alveolar bone and cementum regeneration than the other groups. These findings suggest that MSC-CM enhanced periodontal regeneration due to multiple cytokines contained in MSC-CM.

Parasitism can be a confounding factor in assessing the response of zebra mussels to water contamination

International Nuclear Information System (INIS)

Minguez, Laëtitia; Buronfosse, Thierry; Beisel, Jean-Nicolas; Giambérini, Laure

2012-01-01

Biological responses measured in aquatic organisms to monitor environmental pollution could be also affected by different biotic and abiotic factors. Among these environmental factors, parasitism has often been neglected even if infection by parasites is very frequent. In the present field investigation, the parasite infra-communities and zebra mussel biological responses were studied up- and downstream a waste water treatment plant in northeast France. In both sites, mussels were infected by ciliates and/or intracellular bacteria, but prevalence rates and infection intensities were different according to the habitat. Concerning the biological responses differences were observed related to the site quality and the infection status. Parasitism affects both systems but seemed to depend mainly on environmental conditions. The influence of parasites is not constant, but remains important to consider it as a potential confounding factor in ecotoxicological studies. This study also emphasizes the interesting use of integrative indexes to synthesize data set. Highlights: ► Study of potential bias associated with the use of infected zebra mussels in ecotoxicological studies. ► Presence of infected mussels on banks and channels, up- and downstream a waste water treatment plant. ► Parasitism influence on biological responses dependent of mussel population history. ► Integrative index, an interesting tool to synthesize the set of biological data. - Parasitism influence on the host physiology would be strongly dependent on environmental conditions but remains a potential confounding factor in ecotoxicological studies.

Helminth parasites alter protection against Plasmodium infection.

Science.gov (United States)

Salazar-Castañon, Víctor H; Legorreta-Herrera, Martha; Rodriguez-Sosa, Miriam

2014-01-01

More than one-third of the world's population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host's immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths and Plasmodium affects the host's immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host's susceptibility to subsequent infections by Plasmodium. There are a number of reports on the interactions between helminths and Plasmodium; in some, the burden of Plasmodium parasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodium coinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response.

Cytokines and clustered cardiovascular risk factors in children

DEFF Research Database (Denmark)

Andersen, Lars Bo; Müller, Klaus; Eiberg, Stig

2010-01-01

pronounced in fat and unfit children based on the association with CRP levels. The association between fitness and fatness variables, insulin resistance, and clustered risk could be caused by other mechanisms related to these exposures. The role of IL-6 remains unclear.......The aim was to evaluate the possible role of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), C-reactive protein (CRP), low fitness, and fatness in the early development of clustering of cardiovascular disease (CVD) risk factors and insulin resistance. Subjects for this cross......-sectional study were obtained from 18 schools near Copenhagen, Denmark. Two hundred ten 9-year-old children were selected for cytokine analysis from 434 third-grade children with complete CVD risk profiles. The subgroup was selected according to the CVD risk factor profile (upper and lower quartile of a composite...

Skin rejuvenation using cosmetic products containing growth factors, cytokines, and matrikines: a review of the literature

Directory of Open Access Journals (Sweden)

Aldag C

2016-11-01

Full Text Available Caroline Aldag,1,* Diana Nogueira Teixeira,1,* Phillip S Leventhal2 1Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany; 24Clinics, Paris, France *These authors contributed equally to this work Abstract: Skin aging is primarily due to alterations in the dermal extracellular matrix, especially a decrease in collagen I content, fragmentation of collagen fibrils, and accumulation of amorphous elastin material, also known as elastosis. Growth factors and cytokines are included in several cosmetic products intended for skin rejuvenation because of their ability to promote collagen synthesis. Matrikines and matrikine-like peptides offer the advantage of growth factor-like activities but better skin penetration due to their much smaller molecular size. In this review, we summarize the commercially available products containing growth factors, cytokines, and matrikines for which there is evidence that they promote skin rejuvenation. Keywords: cosmetics, skin, aging, growth factor, cytokine, matrikine

Cytokine expression in mice exposed to diesel exhaust particles by inhalation. Role of tumor necrosis factor

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Loft Steffen

2006-02-01

Full Text Available Abstract Background Particulate air pollution has been associated with lung and cardiovascular disease, for which lung inflammation may be a driving mechanism. The pro-inflammatory cytokine, tumor necrosis factor (TNF has been suggested to have a key-role in particle-induced inflammation. We studied the time course of gene expression of inflammatory markers in the lungs of wild type mice and Tnf-/- mice after exposure to diesel exhaust particles (DEPs. Mice were exposed to either a single or multiple doses of DEP by inhalation. We measured the mRNA level of the cytokines Tnf and interleukin-6 (Il-6 and the chemokines, monocyte chemoattractant protein (Mcp-1, macrophage inflammatory protein-2 (Mip-2 and keratinocyte derived chemokine (Kc in the lung tissue at different time points after exposure. Results Tnf mRNA expression levels increased late after DEP-inhalation, whereas the expression levels of Il-6, Mcp-1 and Kc increased early. The expression of Mip-2 was independent of TNF if the dose was above a certain level. The expression levels of the cytokines Kc, Mcp-1 and Il-6, were increased in the absence of TNF. Conclusion Our data demonstrate that Tnf is not important in early DEP induced inflammation and rather exerts negative influence on Mcp-1 and Kc mRNA levels. This suggests that other signalling pathways are important, a candidate being one involving Mcp-1.

Cytokine-Modulating Strategies and Newer Cytokine Targets for Arthritis Therapy

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Shivaprasad H. Venkatesha

2014-12-01

Full Text Available Cytokines are the key mediators of inflammation in the course of autoimmune arthritis and other immune-mediated diseases. Uncontrolled production of the pro-inflammatory cytokines such as interferon-γ (IFN-γ, tumor necrosis factor α (TNFα, interleukin-6 (IL-6, and IL-17 can promote autoimmune pathology, whereas anti-inflammatory cytokines including IL-4, IL-10, and IL-27 can help control inflammation and tissue damage. The pro-inflammatory cytokines are the prime targets of the strategies to control rheumatoid arthritis (RA. For example, the neutralization of TNFα, either by engineered anti-cytokine antibodies or by soluble cytokine receptors as decoys, has proven successful in the treatment of RA. The activity of pro-inflammatory cytokines can also be downregulated either by using specific siRNA to inhibit the expression of a particular cytokine or by using small molecule inhibitors of cytokine signaling. Furthermore, the use of anti-inflammatory cytokines or cytokine antagonists delivered via gene therapy has proven to be an effective approach to regulate autoimmunity. Unexpectedly, under certain conditions, TNFα, IFN-γ, and few other cytokines can display anti-inflammatory activities. Increasing awareness of this phenomenon might help develop appropriate regimens to harness or avoid this effect. Furthermore, the relatively newer cytokines such as IL-32, IL-34 and IL-35 are being investigated for their potential role in the pathogenesis and treatment of arthritis.

Host and parasite morphology influence congruence between host and parasite phylogenies.

Science.gov (United States)

Sweet, Andrew D; Bush, Sarah E; Gustafsson, Daniel R; Allen, Julie M; DiBlasi, Emily; Skeen, Heather R; Weckstein, Jason D; Johnson, Kevin P

2018-03-23

Comparisons of host and parasite phylogenies often show varying degrees of phylogenetic congruence. However, few studies have rigorously explored the factors driving this variation. Multiple factors such as host or parasite morphology may govern the degree of phylogenetic congruence. An ideal analysis for understanding the factors correlated with congruence would focus on a diverse host-parasite system for increased variation and statistical power. In this study, we focused on the Brueelia-complex, a diverse and widespread group of feather lice that primarily parasitise songbirds. We generated a molecular phylogeny of the lice and compared this tree with a phylogeny of their avian hosts. We also tested for the contribution of each host-parasite association to the overall congruence. The two trees overall were significantly congruent, but the contribution of individual associations to this congruence varied. To understand this variation, we developed a novel approach to test whether host, parasite or biogeographic factors were statistically associated with patterns of congruence. Both host plumage dimorphism and parasite ecomorphology were associated with patterns of congruence, whereas host body size, other plumage traits and biogeography were not. Our results lay the framework for future studies to further elucidate how these factors influence the process of host-parasite coevolution. Copyright © 2018 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Temporal Regulation by Innate Type 2 Cytokines in Food Allergies.

Science.gov (United States)

Graham, Michelle T; Andorf, Sandra; Spergel, Jonathan M; Chatila, Talal A; Nadeau, Kari C

2016-10-01

Food allergies (FAs) are a growing epidemic in western countries with poorly defined etiology. Defined as an adverse immune response to common food allergens, FAs present heterogeneously as a single- or multi-organ response that ranges in severity from localized hives and angioedema to systemic anaphylaxis. Current research focusing on epithelial-derived cytokines contends that temporal regulation by these factors impact initial sensitization and persistence of FA responses upon repeated food allergen exposure. Mechanistic understanding of FA draws insight from a myriad of atopic conditions studied in humans and modeled in mice. In this review, we will highlight how epithelial-derived cytokines initiate and then potentiate FAs. We will also review existing evidence of the contribution of other atopic diseases to FA pathogenesis and whether FA symptoms overlap with other atopic diseases.

The Effect of Repeated Electroacupuncture Analgesia on Neurotrophic and Cytokine Factors in Neuropathic Pain Rats

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Junying Wang

2016-01-01

Full Text Available Chronic pain is a common disability influencing quality of life. Results of previous studies showed that acupuncture has a cumulative analgesic effect, but the relationship with spinal cytokines neurotrophic factors released by astrocytes remains unknown. The present study was designed to observe the effect of electroacupuncture (EA treatment on spinal cytokines neurotrophic factors in chronic neuropathic pain rats. The chronic neuropathic pain was established by chronic constrictive injury (CCI. EA treatment was applied at Zusanli (ST36 and Yanglingquan (GB34 (both bilateral once a day, for 30 min. IL-1β mRNA, TNF-α mRNA, and IL-1 mRNA were detected by quantitative real-time PCR, and the proteins of BDNF, NGF, and NT3/4 were detected by Western blot. The expression levels of cytokines such as IL-1β mRNA, TNF-α mRNA, IL-6 mRNA, and neurotrophic factors such as BDNF, NGF, and NT3/4 in the spinal cord were increased significantly after CCI. The astrocytes released more IL-1β and BDNF after CCI. Repeated EA treatment could suppress the elevated expression of IL-1β mRNA, TNFα mRNA, and BDNF, NGF, and NT3/4 but had no effect on IL-6 mRNA. It is suggested that cytokines and neurotrophic factors which may be closely associated with astrocytes participated in the process of EA relieving chronic pain.

Prevalence and intensity of intestinal parasitic infections and factors ...

African Journals Online (AJOL)

The factors established to be independently associated with presence of intestinal parasitic infection were: age 11-15 years P<0.001, use of plain water for hand washing P<0.05, eating food without spoon P<0.05, consuming raw vegetables P<0.001, untrimmed finger nails P<0.001 and source of drinking water [river ...

Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue.

Science.gov (United States)

Taurone, Samanta; Bianchi, Enrica; Attanasio, Giuseppe; Di Gioia, Cira; Ierinó, Rocco; Carubbi, Cecilia; Galli, Daniela; Pastore, Francesco Saverio; Giangaspero, Felice; Filipo, Roberto; Zanza, Christian; Artico, Marco

2015-07-01

Vestibular schwannomas, also known as acoustic neuromas, are benign tumors, which originate from myelin-forming Schwann cells. They develop in the vestibular branch of the eighth cranial nerve in the internal auditory canal or cerebellopontine angle. The clinical progression of the condition involves slow and progressive growth, eventually resulting in brainstem compression. The objective of the present study was to investigate the expression level and the localization of the pro-inflammatory cytokines, transforming growth factor-β1 (TGF-β1) interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), as well as the adhesion molecules, intracellular adhesion molecule-1 and vascular endothelial growth factor (VEGF), in order to determine whether these factors are involved in the transformation and development of human vestibular schwannoma. The present study investigated whether changes in inflammation are involved in tumor growth and if so, the mechanisms underlying this process. The results of the current study demonstrated that pro-inflammatory cytokines, including TGF-β1, IL-1β and IL-6 exhibited increased expression in human vestibular schwannoma tissue compared with normal vestibular nerve samples. TNF-α was weakly expressed in Schwann cells, confirming that a lower level of this cytokine is involved in the proliferation of Schwann cells. Neoplastic Schwann cells produce pro-inflammatory cytokines that may act in an autocrine manner, stimulating cellular proliferation. In addition, the increased expression of VEGF in vestibular schwannoma compared with that in normal vestibular nerve tissue, suggests that this factor may induce neoplastic growth via the promotion of angiogenesis. The present findings suggest that inflammation may promote angiogenesis and consequently contribute to tumor progression. In conclusion, the results of the present study indicated that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in vestibular

Echinococcus multilocularis and Its Intermediate Host: A Model of Parasite-Host Interplay

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Dominique Angèle Vuitton

2010-01-01

Full Text Available Host-parasite interactions in the E. multilocularis-intermediate host model depend on a subtle balance between cellular immunity, which is responsible for host's resistance towards the metacestode, the larval stage of the parasite, and tolerance induction and maintenance. The pathological features of alveolar echinococcosis. the disease caused by E. multilocularis, are related both to parasitic growth and to host's immune response, leading to fibrosis and necrosis, The disease spectrum is clearly dependent on the genetic background of the host as well as on acquired disturbances of Th1-related immunity. The laminated layer of the metacestode, and especially its carbohydrate components, plays a major role in tolerance induction. Th2-type and anti-inflammatory cytokines, IL-10 and TGF-β, as well as nitric oxide, are involved in the maintenance of tolerance and partial inhibition of cytotoxic mechanisms. Results of studies in the experimental mouse model and in patients suggest that immune modulation with cytokines, such as interferon-α, or with specific antigens could be used in the future to treat patients with alveolar echinococcosis and/or to prevent this very severe parasitic disease.

Influence of Age and Other Factors on Cytokine Expression Profiles in Healthy Children—A Systematic Review

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Marie-Luise Decker

2017-12-01

Full Text Available Cytokines have attracted much attention as diagnostic biomarkers for infectious and inflammatory diseases in recent years. However, understanding of maturation and normal age-associated values is limited. This review summarizes evidence on the influence of age and other factors on expression profiles of soluble and intracellular cytokines in healthy children. IFN-γ, IL-6, IL-10, and TNF-α are the most frequently investigated cytokines, of which an age-associated increase was shown consistently for IFN-γ and TNF-α. An age-associated decrease of IL-13 was seen in resource-limited settings. For other cytokines, including IL-1RA, IL-2, and IL-10, uni- or bimodal curves have been described, and results were influenced by study setting. To conclude, despite limited current understanding of the development of cytokine expression, age clearly influences expression profiles in healthy children. Dynamics of cytokine expression in childhood need to be considered when these are measured in diagnostic assays or as biomarkers. In addition, cytokine-targeting agents may require adjustment for normal values when used in children.

Evaluation of cytokines, oxidative stress markers and brain-derived neurotrophic factor in patients with fibromyalgia - A controlled cross-sectional study.

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Ranzolin, Aline; Duarte, Angela Luzia Branco Pinto; Bredemeier, Markus; da Costa Neto, Cláudio Antônio; Ascoli, Bruna Maria; Wollenhaupt-Aguiar, Bianca; Kapczinski, Flávio; Xavier, Ricardo Machado

2016-08-01

Previous studies measuring serum levels of biomarkers of inflammation/oxidative stress and neurotrophins levels in fibromyalgia (FM) have rendered inconsistent results. In the present study, our aim was to explore the levels of interleukins, oxidative stress markers and brain-derived neurotrophic factor (BDNF) in patients with FM in relation to depression and severity of disease. In a prospective controlled cross-sectional study, serum concentrations of IL-6, IL-8, IL-10, TNF-α, thiobarbituric acid reactive substances (TBARS), protein carbonyl and BDNF were measured in 69 FM patients and 61 healthy controls (all women). In the FM group, the Fibromyalgia Impact Questionnaire (FIQ), the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS) were applied. Mann Whitney's and Spearman correlation tests were used for statistical analysis. The FM patients demonstrated a significant impact of the disease on quality of life (FIQ 70.2±17.8) and most of them had depression at some level (82.6% and 87.0% as assessed by BDI and HDRS, respectively). Most biomarkers (IL-6, IL-8, TNF-α, TBARS and protein carbonyl) and BDNF did not differ significantly between patients and controls, but the IL-10 levels were higher in FM patients (adjusted p=0.041). Among FM patients, there was no correlation of HDRS, FIQ, and BDI scores with any biomarker tested here. We observed no significant differences in biomarkers between FM patients and controls, except for higher levels of IL-10 (an anti-inflammatory cytokine) in patients. The levels of biomarkers were not correlated with parameters of disease and depression severity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cytokines interleukin-1beta and tumor necrosis factor-alpha regulate different transcriptional and alternative splicing networks in primary beta-cells

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Ortis, Fernanda; Naamane, Najib; Flamez, Daisy

2010-01-01

by the cytokines interleukin (IL)-1beta + interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha + IFN-gamma in primary rat beta-cells. RESEARCH DESIGN AND METHODS: Fluorescence-activated cell sorter-purified rat beta-cells were exposed to IL-1beta + IFN-gamma or TNF-alpha + IFN-gamma for 6 or 24 h......-cells, with temporal differences in the number of genes modulated by IL-1beta + IFNgamma or TNF-alpha + IFN-gamma. These cytokine combinations induced differential expression of inflammatory response genes, which is related to differential induction of IFN regulatory factor-7. Both treatments decreased the expression...... of genes involved in the maintenance of beta-cell phenotype and growth/regeneration. Cytokines induced hypoxia-inducible factor-alpha, which in this context has a proapoptotic role. Cytokines also modified the expression of >20 genes involved in RNA splicing, and exon array analysis showed cytokine...

Prevalence and risk factors of intestinal parasitic infections among hill tribe schoolchildren, Northern Thailand

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Tawatchai Apidechkul

2015-09-01

Full Text Available Objective: To study the prevalence and risk factors of intestinal parasitic infections among hill tribe schoolchildren who attended 10 border patrol police schools in 2012, Chiang Rai, Thailand. Methods: A total of 339 subjects were recruited into the study from 2 194 children. Questionnaire was tested for validity and reliability before use. About 5 g stool specimens were collected and investigated for intestinal parasite infections by using cellophane-covered thick smear technique. Logistic regression at α = 0.05 was used to test the associations between variables to find risk factors. Results: There were 339 subjects of whom 51.9% were males and 66.1% were Buddhist; racially 31.2% were Akha and 30.4% were Kmong; mean age was 10.3 years old (minimum = 6, maximum = 16. The prevalence of parasitic infection was 9.7%. After controlling for age, sex, religion, parents’ education levels and parents’ occupations, the only factor that showed a statistically significant association with intestinal parasitic infection was the source of drinking water. The group of drinking mountain piped water had a greater risk of 8.22 times (adjusted odds ratio = 8.22, 95%; confidence interval: 1.07–63.18 compared to the drinking commercially bottled water group, while the group of drinking underground water had a greater risk of 9.83 times (adjusted odds ratio = 9.83, 95%; confidence interval: 0.93–104.12 compared to the drinking commercially bottled water group. Conclusions: Drinking water contaminated by soil was shown to be an important risk factor for intestinal parasitic infection in hill tribe schoolchildren living in mountainous border areas in the northern part of Thailand. Safer alternative drinking water source should be provided along with health education for schools and villagers to be aware of the risk of intestinal parasites from drinking water sources such as mountain piped or underground wells. Such sources are likely to contain higher soil

Cytokine expression in malaria-infected non-human primate placentas

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M.M. Gicheru

2012-06-01

Full Text Available Malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (PM leading to adverse consequences like pre-term deliveries and abortions. Immunological events that take place within the malaria-infected placental micro-environment leading to retarded foetal growth and disruption of pregnancies are among the critical parameters that are still in need of further elucidation. The establishment of more animal models for studying placental malaria can provide novel ways of circumventing problems experienced during placental malaria research in humans such as inaccurate estimation of gestational ages. Using the newly established olive baboon (Papio anubis-Plasmodium knowlesi (P. knowlesi H strain model of placental malaria, experiments were carried out to determine placental cytokine profiles underlying the immunopathogenesis of placental malaria. Four pregnant olive baboons were infected with blood stage P. knowlesi H strain parasites on the one fiftieth day of gestation while four other uninfected pregnant olive baboons were maintained as uninfected controls. After nine days of infection, placentas were extracted from all the eight baboons through cesarean surgery and used for the processing of placental plasma and sera samples for cytokine sandwich enzyme linked immunosorbent assays (ELISA. Results indicated that the occurrence of placental malaria was associated with elevated concentrations of tumour necrosis factor alpha (TNF-α and interleukin 12 (IL-12. Increased levels of IL-4, IL-6 and IL-10 and interferon gamma (IFN-γ levels were detected in uninfected placentas. These findings match previous reports regarding immunity during PM thereby demonstrating the reliability of the olive baboon-P. knowlesi model for use in further studies.

Myeloid-derived suppressor cell functionality and interaction with Leishmania major parasites differ in C57BL/6 and BALB/c mice.

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Schmid, Maximilian; Zimara, Nicole; Wege, Anja Kathrin; Ritter, Uwe

2014-11-01

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of CD11b+ cells. According to the surface molecules Ly6G and Ly6C (where Ly6G and Ly6C are lymphocyte antigen 6, locus G and C, respectively), MDSCs are further divided into monocytic (Mo-MDSCs, CD11b+ /Ly6C(high) /Ly6G-) and polymorphonucleated suppressor cells (PMN-MDSCs, CD11b+ /Ly6C(int) /Ly6G+). Most published manuscripts focus on the suppressive role of MDSCs in cancer, whereas their impact on adaptive immunity against obligatory intracellular parasites is not well understood. Furthermore, it is not clear how the genetic background of mice influences MDSC functionality. Therefore, we implemented an experimental model of leishmaniasis, and analyzed MDSC maturation and the impact of MDSCs on the parasite-specific T-cell responses in resistant C57BL/6 and susceptible BALB/c mice. This experimental setup demonstrated the impaired ability of BALB/c mice to produce Mo-MDSCs when compared with C57BL/6 mice. This phenotype is detectable after subcutaneous infection with parasites and is specifically represented by a reduced accumulation of Mo-MDSCs at the site of infection in BALB/c mice. Moreover, infected C57BL/6-derived MDSCs were able to suppress Leishmania-specific CD4+ -cell proliferation, whereas BALB/c-derived MDSCs harboring parasites lost this suppressive function. In conclusion, we demonstrate that (i) genetic background defines MDSC differentiation; and (ii) Leishmania major parasites are able to modulate the suppressive effect of MDSCs in a strain-dependent manner. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Risk factors with the occurrence of parasites and coliform in vegetables from an agroindustry

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Francisco Rafael Martins Soto

Full Text Available ABSTRACT In this study, we evaluated the risk factors associated with the occurrence of total coliforms, thermotolerant coliforms, and intestinal parasite eggs in vegetables from an agroindustry in the city of Ibiúna - SP, Brazil. A questionnaire with 17 questions was applied to 24 producers to carry out a diagnosis of the risk factors and their posterior association or not with total coliforms, thermotolerant coliforms, and intestinal parasite eggs. The questions addressed mainly the production system, fertilizer used, source of the water used for irrigation, sanitization of the vegetables, and form of transport. For the investigation of total coliforms, thermotolerant coliforms, and intestinal parasite eggs, the samples were processed at the microbiology and parasitology laboratory of the Federal Institute of São Paulo, São Roque Campus. The results revealed that total coliforms were found in 100% of the investigated samples and thermotolerant coliforms were detected in 95.83% of the samples. There was a significant statistical association for the risk factor use of reservoir water, where there was release of wastewater and absence of sanitization of the vegetables at the moment of harvest in relation to the presence of thermotolerant coliforms. Intestinal parasite eggs were found in 33.33% of the samples.

Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF).

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Masuki, Hideo; Okudera, Toshimitsu; Watanebe, Taisuke; Suzuki, Masashi; Nishiyama, Kazuhiko; Okudera, Hajime; Nakata, Koh; Uematsu, Kohya; Su, Chen-Yao; Kawase, Tomoyuki

2016-12-01

The development of platelet-rich fibrin (PRF) drastically simplified the preparation procedure of platelet-concentrated biomaterials, such as platelet-rich plasma (PRP), and facilitated their clinical application. PRF's clinical effectiveness has often been demonstrated in pre-clinical and clinical studies; however, it is still controversial whether growth factors are significantly concentrated in PRF preparations to facilitate wound healing and tissue regeneration. To address this matter, we performed a comparative study of growth factor contents in PRP and its derivatives, such as advanced PRF (A-PRF) and concentrated growth factors (CGF). PRP and its derivatives were prepared from the same peripheral blood samples collected from healthy donors. A-PRF and CGF preparations were homogenized and centrifuged to produce extracts. Platelet and white blood cell counts in A-PRF and CGF preparations were determined by subtracting those counts in red blood cell fractions, supernatant acellular serum fractions, and A-PRF/CGF exudate fractions from those counts of whole blood samples. Concentrations of growth factors (TGF-β1, PDGF-BB, VEGF) and pro-inflammatory cytokines (IL-1β, IL-6) were determined using ELISA kits. Compared to PRP preparations, both A-PRF and CGF extracts contained compatible or higher levels of platelets and platelet-derived growth factors. In a cell proliferation assay, both A-PRF and CGF extracts significantly stimulated the proliferation of human periosteal cells without significant reduction at higher doses. These data clearly demonstrate that both A-PRF and CGF preparations contain significant amounts of growth factors capable of stimulating periosteal cell proliferation, suggesting that A-PRF and CGF preparations function not only as a scaffolding material but also as a reservoir to deliver certain growth factors at the site of application.

Serum levels of cytokines in water buffaloes experimentally infected with Fasciola gigantica.

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Zhang, Fu-Kai; Guo, Ai-Jiang; Hou, Jun-Ling; Sun, Miao-Miao; Sheng, Zhao-An; Zhang, Xiao-Xuan; Huang, Wei-Yi; Elsheikha, Hany M; Zhu, Xing-Quan

2017-09-15

Fasciola gigantica infection in water buffaloes causes significant economic losses especially in developing countries. Although modulation of the host immune response by cytokine neutralization or vaccination is a promising approach to control infection with this parasite, our understanding of cytokine's dynamic during F. gigantica infection is limited. To address this, we quantified the levels of serum cytokines produced in water buffaloes following experimental infection with F. gigantica. Five buffaloes were infected via oral gavage with 500 viable F. gigantica metacercariae and blood samples were collected from buffaloes one week before infection and for 13 consecutive weeks thereafter. The levels of 10 cytokines in serum samples were simultaneously determined using ELISA. F. gigantica failed to elicit the production of various pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-2, IL-6, IL-12, and IFN-γ. On the other hand, evidence of a Th2 type response was detected, but only early in the course of parasite colonization and included modest increase in the levels of IL-10 and IL-13. The results also revealed suppression of the immune responses as a feature of chronic F. gigantica infection in buffaloes. Taken together, F. gigantica seems to elicit a modest Th2 response at early stage of infection in order to downregulate harmful Th1- and Th17-type inflammatory responses in experimentally infected buffaloes. The full extent of anti-F. gigantica immune response and its relation to pathogenesis requires further study. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of trans-stilbene and terphenyl compounds on different strains of Leishmania and on cytokines production from infected macrophages.

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Bruno, Federica; Castelli, Germano; Vitale, Fabrizio; Giacomini, Elisa; Roberti, Marinella; Colomba, Claudia; Cascio, Antonio; Tolomeo, Manlio

2018-01-01

Most of the antileishmanial modern therapies are not satisfactory due to high toxicity or emergence of resistance and high cost of treatment. Previously, we observed that two compounds of a small library of trans-stilbene and terphenyl derivatives, ST18 and TR4, presented the best activity and safety profiles against Leishmania infantum promastigotes and amastigotes. In the present study we evaluated the effects of ST18 and the TR4 in 6 different species of Leishmania and the modifications induced by these two compounds in the production of 8 different cytokines from infected macrophages. We observed that TR4 was potently active in all Leishmania species tested in the study showing a leishmanicidal activity higher than that of ST18 and meglumine antimoniate in the most of the species. Moreover, TR4 was able to decrease the levels of IL-10, a cytokine able to render the host macrophage inactive allowing the persistence of parasites inside its phagolysosome, and increase the levels of IL-1β, a cytokine important for host resistance to Leishmania infection by inducible iNOS-mediated production of NO, and IL-18, a cytokine implicated in the development of Th1-type immune response. Copyright © 2017 Elsevier Inc. All rights reserved.

Cellular and molecular mechanisms of chronic rhinosinusitis and potential therapeutic strategies: review on cytokines, nuclear factor kappa B and transforming growth factor beta.

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Phan, N T; Cabot, P J; Wallwork, B D; Cervin, A U; Panizza, B J

2015-07-01

Chronic rhinosinusitis is characterised by persistent inflammation of the sinonasal mucosa. Multiple pathophysiological mechanisms are likely to exist. Previous research has focused predominantly on T-helper type cytokines to highlight the inflammatory mechanisms. However, proteins such as nuclear factor kappa B and transforming growth factor beta are increasingly recognised to have important roles in sinonasal inflammation and tissue remodelling. This review article explores the roles of T-helper type cytokines, nuclear factor kappa B and transforming growth factor beta in the pathophysiological mechanisms of chronic rhinosinusitis. An understanding of these mechanisms will allow for better identification and classification of chronic rhinosinusitis endotypes, and, ultimately, improved therapeutic strategies.

Barrier abnormalities and keratinocyte-derived cytokine cascade after cessation of long-term topical glucocorticosteroid on hairless mouse skin

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Tzu-Kai Lin

2015-06-01

Conclusion: An epidermis-derived cytokine cascade was observed following TCS-induced barrier disruption, which is similar to that from permeability barrier insults by acetone or tape stripping. The study suggests that concurrent application of skin care products during TCS treatment improves barrier homeostasis, and should become a standard practice to alleviate TCS-induced WD.

Sex and death: the effects of innate immune factors on the sexual reproduction of malaria parasites.

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Ricardo S Ramiro

2011-03-01

Full Text Available Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. Recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria parasites adjust their sex ratios in response to infection genetic diversity, precisely as predicted. Theory also predicts that parasites should adjust sex allocation in response to host immunity. Whilst data are supportive, the assumptions underlying this prediction - that host immune responses have differential effects on the mating ability of males and females - have not yet been tested. Here, we combine experimental work with theoretical models in order to investigate whether the development and fertility of male and female parasites is affected by innate immune factors and develop new theory to predict how parasites' sex allocation strategies should evolve in response to the observed effects. Specifically, we demonstrate that reactive nitrogen species impair gametogenesis of males only, but reduce the fertility of both male and female gametes. In contrast, tumour necrosis factor-α does not influence gametogenesis in either sex but impairs zygote development. Therefore, our experiments demonstrate that immune factors have complex effects on each sex, ranging from reducing the ability of gametocytes to develop into gametes, to affecting the viability of offspring. We incorporate these results into theory to predict how the evolutionary trajectories of parasite sex ratio strategies are shaped by sex differences in gamete production, fertility and offspring development. We show that medical interventions targeting offspring development are more likely

Helminths and skewed cytokine profiles increase tuberculin skin test positivity in Warao Amerindians

NARCIS (Netherlands)

Verhagen, L. M.; Hermans, P. W. M.; Warris, A.; de Groot, R.; Maes, M.; Villalba, J. A.; del Nogal, B.; van den Hof, S.; Mughini Gras, L.; van Soolingen, D.; Pinelli, E.; de Waard, J. H.

2012-01-01

The immune regulatory mechanisms involved in the acquisition of Mycobacterium tuberculosis infection in children are largely unknown. We investigated the influence of parasitic infections, malnutrition and plasma cytokine profiles on tuberculin skin test (TST) positivity in Warao Amerindians in

Donor lung derived myeloid and plasmacytoid dendritic cells differentially regulate T cell proliferation and cytokine production

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Benson Heather L

2012-03-01

Full Text Available Abstract Background Direct allorecognition, i.e., donor lung-derived dendritic cells (DCs stimulating recipient-derived T lymphocytes, is believed to be the key mechanism of lung allograft rejection. Myeloid (cDCs and plasmacytoid (pDCs are believed to have differential effects on T cell activation. However, the roles of each DC type on T cell activation and rejection pathology post lung transplantation are unknown. Methods Using transgenic mice and antibody depletion techniques, either or both cell types were depleted in lungs of donor BALB/c mice (H-2d prior to transplanting into C57BL/6 mice (H-2b, followed by an assessment of rejection pathology, and pDC or cDC-induced proliferation and cytokine production in C57BL/6-derived mediastinal lymph node T cells (CD3+. Results Depleting either DC type had modest effect on rejection pathology and T cell proliferation. In contrast, T cells from mice that received grafts depleted of both DCs did not proliferate and this was associated with significantly reduced acute rejection scores compared to all other groups. cDCs were potent inducers of IFNγ, whereas both cDCs and pDCs induced IL-10. Both cell types had variable effects on IL-17A production. Conclusion Collectively, the data show that direct allorecognition by donor lung pDCs and cDCs have differential effects on T cell proliferation and cytokine production. Depletion of both donor lung cDC and pDC could prevent the severity of acute rejection episodes.

Generalized Liver- and Blood-Derived CD8+ T-Cell Impairment in Response to Cytokines in Chronic Hepatitis C Virus Infection.

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Stephanie C Burke Schinkel

Full Text Available Generalized CD8+ T-cell impairment in chronic hepatitis C virus (HCV infection and the contribution of liver-infiltrating CD8+ T-cells to the immunopathogenesis of this infection remain poorly understood. It is hypothesized that this impairment is partially due to reduced CD8+ T-cell activity in response to cytokines such as IL-7, particularly within the liver. To investigate this, the phenotype and cytokine responsiveness of blood- and liver-derived CD8+ T-cells from healthy controls and individuals with HCV infection were compared. In blood, IL-7 receptor α (CD127 expression on bulk CD8+ T-cells in HCV infection was no different than controls yet was lower on central memory T-cells, and there were fewer naïve cells. IL-7-induced signalling through phosphorylated STAT5 was lower in HCV infection than in controls, and differed between CD8+ T-cell subsets. Production of Bcl-2 following IL-7 stimulation was also lower in HCV infection and inversely related to the degree of liver fibrosis. In liver-derived CD8+ T-cells, STAT5 activation could not be increased with cytokine stimulation and basal Bcl-2 levels of liver-derived CD8+ T-cells were lower than blood-derived counterparts in HCV infection. Therefore, generalized CD8+ T-cell impairment in HCV infection is characterized, in part, by impaired IL-7-mediated signalling and survival, independent of CD127 expression. This impairment is more pronounced in the liver and may be associated with an increased potential for apoptosis. This generalized CD8+ T-cell impairment represents an important immune dysfunction in chronic HCV infection that may alter patient health.

Proliferative and antiproliferative effects of interferon-gamma and tumor necrosis factor-alpha on cell lines derived from cervical and ovarian malignancies

International Nuclear Information System (INIS)

Mutch, D.G.; Massad, L.S.; Kao, M.S.; Collins, J.L.

1990-01-01

Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three human cell lines derived from ovarian carcinomas (SK-OV-3, Caov-3, and NIH:OVCAR-3) were analyzed in vitro to determine the effect of recombinant interferon-gamma and recombinant human tumor necrosis factor-alpha on cell growth and survival. The effects of interferon-gamma, tumor necrosis factor-alpha, and both interferon-gamma and tumor necrosis factor-alpha on cell growth were measured after 24 and 72 hours of incubation by the incorporation of chromium 51. The results of this analysis showed that all seven cell lines were resistant to the antiproliferative action of tumor necrosis factor-alpha, that the growth of most cell lines was inhibited by interferon-gamma by 72 hours of incubation, and that after 72 hours of incubation all cell lines demonstrated a synergistic antiproliferative response to the combination of interferon-gamma and tumor necrosis factor-alpha. However, the effects of these cytokines on cell growth were found to differ among cell lines and varied with the concentration and the duration of incubation. The growth of one cell line (Caov-3) was stimulated by both tumor necrosis factor-alpha and interferon-gamma. These results suggest that the clinical effects of these cytokines on the growth of gynecologic cancers may be more complex than previously supposed

The landscape of human genes involved in the immune response to parasitic worms

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Fumagalli Matteo

2010-08-01

Full Text Available Abstract Background More than 2 billion individuals worldwide suffer from helminth infections. The highest parasite burdens occur in children and helminth infection during pregnancy is a risk factor for preterm delivery and reduced birth weight. Therefore, helminth infections can be regarded as a strong selective pressure. Results Here we propose that candidate susceptibility genes for parasitic worm infections can be identified by searching for SNPs that display a strong correlation with the diversity of helminth species/genera transmitted in different geographic areas. By a genome-wide search we identified 3478 variants that correlate with helminth diversity. These SNPs map to 810 distinct human genes including loci involved in regulatory T cell function and in macrophage activation, as well as leukocyte integrins and co-inhibitory molecules. Analysis of functional relationships among these genes identified complex interaction networks centred around Th2 cytokines. Finally, several genes carrying candidate targets for helminth-driven selective pressure also harbour susceptibility alleles for asthma/allergy or are involved in airway hyper-responsiveness, therefore expanding the known parallelism between these conditions and parasitic infections. Conclusions Our data provide a landscape of human genes that modulate susceptibility to helminths and indicate parasitic worms as one of the major selective forces in humans.

Mechanism-based design of parasite-targeted artemisinin derivatives: synthesis and antimalarial activity of new diamine containing analogues.

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Hindley, Stephen; Ward, Stephen A; Storr, Richard C; Searle, Natalie L; Bray, Patrick G; Park, B Kevin; Davies, Jill; O'Neill, Paul M

2002-02-28

The potent antimalarial activity of chloroquine against chloroquine-sensitive strains can be attributed, in part, to its high accumulation in the acidic environment of the heme-rich parasite food vacuole. A key component of this intraparasitic chloroquine accumulation mechanism is a weak base "ion-trapping" effect whereupon the basic drug is concentrated in the acidic food vacuole in its membrane-impermeable diprotonated form. By the incorporation of amino functionality into target artemisinin analogues, we hoped to prepare a new series of analogues that, by virtue of increased accumulation into the ferrous-rich vacuole, would display enhanced antimalarial potency. The initial part of the project focused on the preparation of piperazine-linked analogues (series 1 (7-16)). Antimalarial evaluation of these derivatives demonstrated potent activity versus both chloroquine-sensitive and chloroquine-resistant parasites. On the basis of these observations, we then set about preparing a series of C-10 carba-linked amino derivatives. Optimization of the key synthetic step using a newly developed coupling protocol provided a key intermediate, allyldeoxoartemisinin (17) in 90% yield. Further elaboration, in three steps, provided nine target C-10 carba analogues (series 2 (21-29)) in good overall yields. Antimalarial assessment demonstrated that these compounds were 4-fold more potent than artemisinin and about twice as active as artemether in vitro versus chloroquine-resistant parasites. On the basis of the products obtained from biomimetic Fe(II) degradation of the C-10 carba analogue (23), we propose that these analogues may have a mode of action subtly different from that of the parent drug artemisinin (series 1 (7-16)) and other C-10 ether derivatives such as artemether. Preliminary in vivo testing by the WHO demonstrated that four of these compounds are active orally at doses of less than 10 mg/kg. Since these analogues are available as water-soluble salts and cannot

Cytokine profile and pathology in human leishmaniasis

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Ribeiro-de-Jesus A.

1998-01-01

Full Text Available The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. In humans, production of IFN-g is associated with the control of infection in children infected by Leishmania chagasi. In visceral leishmaniasis, an impairment in IFN-g production and high IL-4 and IL-10 levels (Th2 cytokines are observed in antigen-stimulated peripheral blood mononuclear cells (PBMC. Moreover, IL-12 restores IFN-g production and enhances the cytotoxic response. IL-10 is the cytokine involved in down-regulation of IFN-g production, since anti-IL-10 monoclonal antibody (mAb restores in vitro IFN-g production and lymphoproliferative responses, and IL-10 abrogates the effect of IL-12. In cutaneous and mucosal leishmaniasis, high levels of IFN-g are found in L. amazonensis-stimulated PBMC. However, low or absent IFN-g levels were observed in antigen-stimulated PBMC from 50% of subjects with less than 60 days of disease (24 ± 26 pg/ml. This response was restored by IL-12 (308 ± 342 pg/ml and anti-IL-10 mAb (380 ± 245 pg/ml (P<0.05. Later during the disease, high levels of IFN-g and TNF-a are produced both in cutaneous and mucosal leishmaniasis. After treatment there is a decrease in TNF-a levels (366 ± 224 pg/ml before treatment vs 142 ± 107 pg/ml after treatment, P = 0.02. Although production of IFN-g and TNF-a might be involved in the control of parasite multiplication in the early phases of Leishmania infection, these cytokines might also be involved in the tissue damage seen in tegumentary leishmaniasis

Cytokines as endogenous pyrogens.

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Dinarello, C A

1999-03-01

Cytokines are pleiotropic molecules mediating several pathologic processes. Long before the discovery of cytokines as immune system growth factors or as bone marrow stimulants, investigators learned a great deal about cytokines when they studied them as the endogenous mediators of fever. The terms "granulocytic" or "endogenous pyrogen" were used to describe substances with the biologic property of fever induction. Today, we recognize that pyrogenicity is a fundamental biologic property of several cytokines and hence the clinically recognizeable property of fever links host perturbations during disease with fundamental perturbations in cell biology. In this review, the discoveries made on endogenous pyrogens are revisited, with insights into the importance of the earlier work to the present-day understanding of cytokines in health and in disease.

Effect of atopic skin stressors on natural moisturizing factors and cytokines in healthy adult epidermis

DEFF Research Database (Denmark)

Engebretsen, K A; Kezic, S; Jakasa, I

2018-01-01

: To explore the effect of selected exogenous skin stressors on NMF and skin cytokines levels in healthy adult epidermis. MATERIAL AND METHODS: 40 healthy volunteers (18-49 years) were exposed to hard, soft, and chlorinated water, 0.5% SLS, house dust mite, cat allergen, staphylococcal enterotoxin B (SEB...... of various skin cytokines in healthy individuals. Our data highlight environmental factors that might play a role in AD pathophysiology, but needs confirmation in AD patients. This article is protected by copyright. All rights reserved....

Chalcones from Chinese liquorice inhibit proliferation of T cells and production of cytokines

DEFF Research Database (Denmark)

Barfod, Lea; Kemp, Kåre; Hansen, Majbritt

2002-01-01

Licochalcone A (LicA), an oxygenated chalcone, has been shown to inhibit the growth of both parasites and bacteria. In this study, we investigated the effect of LicA and four synthetic analogues on the activity of human peripheral blood mononuclear cell proliferation and cytokine production. Four...... out of five chalcones tested inhibited the proliferation of lymphocytes measured by thymidine incorporation and by flow cytometry. The production of pro- and anti-inflammatory cytokines from monocytes and T cells was also inhibited by four of five chalcones. Furthermore, intracellular detection...... of cytokines revealed that the chalcones inhibited the production rather than the release of the cytokines. Taken together, these results indicate that LicA and some analogues may have immunomodulatory effects, and may thus be candidates not only as anti-microbial agents, but also for the treatment of other...

Endothelial-derived GM-CSF influences expression of oncostatin M

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During and following transendothelial migration, neutrophils undergo a number of phenotypic changes resulting from encounters with endothelial-derived factors. This report uses an in vitro model with HUVEC and isolated human neutrophils to examine the effects of two locally-derived cytokines, granul...

Th-17 regulatory cytokines IL-21, IL-23, and IL-6 enhance neutrophil production of IL-17 cytokines during asthma.

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Halwani, Rabih; Sultana, Asma; Vazquez-Tello, Alejandro; Jamhawi, Amer; Al-Masri, Abeer A; Al-Muhsen, Saleh

2017-11-01

In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils. Peripheral blood neutrophils isolated from asthmatics were stimulated with IL-21, IL-23, and IL-6 cytokines and their ability to produce IL-17A and IL-17F was determined relative to healthy controls. Signal transducer and activator of transcription 3 (STAT3) phosphorylation levels were measured in stimulated neutrophil using flow cytometry. The requirement for STAT3 phosphorylation was determined by blocking its activation using a specific chemical inhibitor. Stimulating asthmatic neutrophils with IL-21, 23, and 6 enhanced the production of IL-17A and IL-17F at significantly higher levels comparatively to healthy controls. Stimulating neutrophils with IL-21, IL-23, and IL-6 cytokines enhanced STAT3 phosphorylation, in all cases. Interestingly, inhibiting STAT3 phosphorylation using a specific chemical inhibitor dramatically blocked the ability of neutrophils to produce IL-17, demonstrating that STAT3 activation is the major factor mediating IL-17 gene expression. These findings suggest that neutrophil infiltration in lungs of severe asthmatics may represent an important source of pro-inflammatory IL-17A and -F cytokines, a production enhanced by Th-17 regulatory cytokines, and thus providing a feedback mechanism that sustains inflammation. Our results suggest that STAT3 pathway could be a potential target for regulating neutrophilic inflammation during severe asthma.

RSV-Induced H3K4 Demethylase KDM5B Leads to Regulation of Dendritic Cell-Derived Innate Cytokines and Exacerbates Pathogenesis In Vivo

DEFF Research Database (Denmark)

Ptaschinski, Catherine; Mukherjee, Sumanta; Moore, Martin L

2015-01-01

-transfected cells. The generation of Kdm5bfl/fl-CD11c-Cre+ mice recapitulated the latter results during in vitro DC activation showing innate cytokine modulation. In vivo, infection of Kdm5bfl/fl-CD11c-Cre+ mice with RSV resulted in higher production of IFN-γ and reduced IL-4 and IL-5 compared to littermate....../fl-CD11c-CRE mice were used, the exacerbated response was abrogated. Importantly, human monocyte-derived DCs treated with a chemical inhibitor for KDM5B resulted in increased innate cytokine levels as well as elicited decreased Th2 cytokines when co-cultured with RSV reactivated CD4+ T cells...

Longitudinal Study of Cytokine Expression, Lipid Profile and Neuronal Growth Factors in Human Breast Milk from Term and Preterm Deliveries

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Maria Carmen Collado

2015-10-01

Full Text Available Breast milk (BM is considered as a reference for infant nutrition. The role of bioactive components, such as cytokines, hormones, growth factors (GFs and fatty acids (FAs is poorly known, but they might be implicated in immune response development. The aim of this study was to identify the lipid profile and the spectrum of cytokines and neuronal GF in BM samples and analyse the influence of gestational age and lactation time on these components. This study used a longitudinal prospective method for the characterization of cytokines, FAs and GFs global profiles in 120 BM samples from 40 healthy mothers (20 preterm and 20 term collected as colostrum, transitional and mature milk. The cytokines were analysed by protein array (Ray Bio® Human Cytokine Array G6. Ray Biotech, Inc. Norcross, GA, USA and the FAs were analysed by gas chromatography. The FA profile was similar between the term and the preterm BM samples. Omega-3-α-linoleic and docosahexaenoic acid (DHA and omega-6-linoleic acid were the most abundant in the term and preterm samples during lactation. Omega-3 ETA and omega-3 EPA we observed exclusively in the preterm samples. The cytokine profile showed a different trend based on gestational age. A significantly higher expression of neurotrophic factors was found in the mature preterm milk samples as compared to the mature term samples. Our study is the first to identify the influence and interactions of perinatal factors on cytokine, GFs and FAs in human milk.

Prevalence and Risk Factors of Human Intestinal Parasites in Roudehen, Tehran Province, Iran.

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Hemmati, Nasrin; Razmjou, Elham; Hashemi-Hafshejani, Saeideh; Motevalian, Abbas; Akhlaghi, Lameh; Meamar, Ahmad Reza

2017-01-01

Intestinal parasitic infections are among the most common infections and health problems worldwide. Due to the lack of epidemiologic information of such infections, the prevalence of, and the risk factors for, enteric parasites were investigated in residents of Roudehen, Tehran Province, Iran. In this cross-sectional study, 561 triple fecal samples were collected through a two-stage cluster-sampling protocol from Jun to Dec 2014. The samples were examined by formalin-ether concentration, culture, and with molecular methods. The prevalence of enteric parasites was 32.7% (95% CI 27.3-38). Blastocystis sp. was the most common intestinal protozoan (28.4%; 95% CI 23.7-33.0). The formalin-ether concentration and culture methods detected Blastocystis sp., Entamoeba coli , Giardia intestinalis , Dientamoeba fragilis , Iodamoeba butschlii , Entamoeba complex cysts or trophozoite , Chilomastix mesnilii , and Enterobius vermicularis . Single-round PCR assay for Entamoeba complex were identified Entamoeba dispar and E. moshkovskii . E. histolytica was not observed in any specimen. Multivariate analysis showed a significant association of parasites with water source and close animal contact. There was no correlation between infections and gender, age, occupation, education, or travel history. Protozoan infections were more common than helminth infections. This study revealed a high prevalence of enteric protozoan parasite infection among citizens of Rodehen. As most of the species detected are transmitted through a water-resistant cyst, public and individual education on personal hygiene should be considered to reduce transmission of intestinal parasites in the population.

Surface antigens and potential virulence factors from parasites detected by comparative genomics of perfect amino acid repeats

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Adler Joël

2007-12-01

Full Text Available Abstract Background Many parasitic organisms, eukaryotes as well as bacteria, possess surface antigens with amino acid repeats. Making up the interface between host and pathogen such repetitive proteins may be virulence factors involved in immune evasion or cytoadherence. They find immunological applications in serodiagnostics and vaccine development. Here we use proteins which contain perfect repeats as a basis for comparative genomics between parasitic and free-living organisms. Results We have developed Reptile http://reptile.unibe.ch, a program for proteome-wide probabilistic description of perfect repeats in proteins. Parasite proteomes exhibited a large variance regarding the proportion of repeat-containing proteins. Interestingly, there was a good correlation between the percentage of highly repetitive proteins and mean protein length in parasite proteomes, but not at all in the proteomes of free-living eukaryotes. Reptile combined with programs for the prediction of transmembrane domains and GPI-anchoring resulted in an effective tool for in silico identification of potential surface antigens and virulence factors from parasites. Conclusion Systemic surveys for perfect amino acid repeats allowed basic comparisons between free-living and parasitic organisms that were directly applicable to predict proteins of serological and parasitological importance. An on-line tool is available at http://genomics.unibe.ch/dora.

Analysis of the cytokine profile in spleen cells from dogs naturally infected by Leishmania chagasi.

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Lage, R S; Oliveira, G C; Busek, S U; Guerra, L L; Giunchetti, R C; Corrêa-Oliveira, R; Reis, A B

2007-01-15

Recent studies suggest that asymptomatic dogs infected with canine visceral leishmaniasis (CVL) develop a Th1 immunological profile whilst oligosymptomatic and symptomatic CVL-infected animals present a Th2 profile. In the present study, an RT-PCR method has been standardised and employed to evaluate the frequency and the semi-quantitative level of expression of the cytokines IL-4, IL-10, IL-12, INF-gamma and TNF-alpha in splenocytes of 30 dogs naturally infected with Leishmania chagasi and of 7 non-infected dogs (NID). An increase in the level of expression of IL-12 (p=0.059) was detected in all CVL-infected dogs compared with NID. In dogs exhibiting high parasitism, the frequency of expression of IL-10 was higher (p=0.011) than in animals presenting low parasitism or medium parasitism (MP) and in NID animals, whilst the level of expression of IL-10 was higher (p=0.0094) than in animals exhibiting MP and in the NID group. Positive correlations between the levels of expression of IL-10 with respect to the progression of the disease (IL-10: r=0.3510; p=0.0337) and the levels of expression of IL-10 and INF-gamma increase in parasitism (IL-10: r=0.3428; p=0.0438 and INF-gamma: r=0.4690; p=0.0045) were observed. Such data suggest that CVL is marked by a balanced production of Th1 and Th2 cytokines, with a predominant accumulation of IL-10 as a consequence of an increase in parasitic load and progression of the disease, and INF-gamma was related with the increase in parasitic load.

Pro-inflammatory Cytokine Response and Genetic Diversity in Merozoite Surface Protein 2 of Plasmodium falciparum Isolates from Nigeria.

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Ajibaye, Olusola; Osuntoki, Akinniyi A; Ebuehi, Albert Ot; Iwalokun, Bamidele A; Balogun, Emmanuel O; Egbuna, Kathleen N

2017-01-01

Polymorphisms in Plasmodium falciparum merozoite surface protein-2 ( msp -2) and associated parasite genetic diversity which varies between malaria-endemic regions remain a limitation in malaria vaccine development. Pro-inflammatory cytokines are important in immunity against malaria, understanding the influence of genetic diversity on cytokine response is important for effective vaccine design. P. falciparum isolates obtained from 300 Nigerians with uncomplicated falciparum malaria at Ijede General Hospital, Ijede (IJE), General Hospital Ajeromi, Ajeromi (AJE) and Saint Kizito Mission Hospital, Lekki, were genotyped by nested polymerase chain reaction of msp -2 block 3 while ELISA was used to determine the pro-inflammatory cytokine response to describe the genetic diversity of P. falciparum . Eighteen alleles were observed for msp -2 loci. Of the 195 isolates, 61 (31.0%) had only FC27-type alleles, 38 (19.7%) had only 3D7-type alleles, and 49.3% had multiple parasite lines with both alleles. Band sizes were 275-625 bp for FC27 and 150-425 bp for 3D7. Four alleles were observed from LEK, 2 (375-425 bp) and 2 (275-325 bp) of FC27-and 3D7-types, respectively; 12 alleles from AJE, 9 (275-625 bp) and 3 (325-425 bp) of FC27-types and 3D7-types, respectively; while IJE had a total of 12 alleles, 9 (275-625 bp) and 3 (325-425 bp) of FC27-types and 3D7-types, respectively. Mean multiplicity of infection (MOI) was 1.54. Heterozygosity ( H E ) ranged from 0.77 to 0.87 and was highest for IJE (0.87). Cytokine response was higher among 0.05) but with neither parasite density nor infection type. P. falciparum genetic diversity is extensive in Nigeria, protection via pro-inflammatory cytokines have little or no interplay with infection multiplicity.

Caspase-8 regulates the expression of pro- and anti-inflammatory cytokines in human bone marrow-derived mesenchymal stromal cells.

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Moen, Siv H; Westhrin, Marita; Zahoor, Muhammad; Nørgaard, Nikolai N; Hella, Hanne; Størdal, Berit; Sundan, Anders; Nilsen, Nadra J; Sponaas, Anne-Marit; Standal, Therese

2016-09-01

Mesenchymal stem cells, also called mesenchymal stromal cells, MSCs, have great potential in stem cell therapy partly due to their immunosuppressive properties. How these cells respond to chronic inflammatory stimuli is therefore of importance. Toll-like receptors (TLR)s are innate immune receptors that mediate inflammatory signals in response to infection, stress, and damage. Caspase-8 is involved in activation of NF-kB downstream of TLRs in immune cells. Here we investigated the role of caspase-8 in regulating TLR-induced cytokine production from human bone marrow-derived mesenchymal stromal cells (hBMSCs). Cytokine expression in hBMCs in response to poly(I:C) and LPS was evaluated by PCR, multiplex cytokine assay, and ELISA. TLR3, TRIF, and caspase-8 were silenced using siRNA. Caspase-8 was also inhibited using a caspase-8 inhibitor, z-IEDT. We found that TLR3 agonist poly(I:C) and TLR4 agonist LPS induced secretion of several pro-inflammatory cytokines in a TLR-dependent manner which required the TLR signaling adaptor molecule TRIF. Further, poly(I:C) reduced the expression of anti-inflammatory cytokines HGF and TGFβ whereas LPS reduced HGF expression only. Notably, caspase-8 was involved in the induction of IL- IL-1β, IL-6, CXCL10, and in the inhibition of HGF and TGFβ. Caspase-8 appears to modulate hBMSCs into gaining a pro-inflammatory phenotype. Therefore, inhibiting caspase-8 in hBMSCs might promote an immunosuppressive phenotype which could be useful in clinical applications to treat inflammatory disorders.

Caspase‐8 regulates the expression of pro‐ and anti‐inflammatory cytokines in human bone marrow‐derived mesenchymal stromal cells

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Moen, Siv H.; Westhrin, Marita; Zahoor, Muhammad; Nørgaard, Nikolai N.; Hella, Hanne; Størdal, Berit; Sundan, Anders; Nilsen, Nadra J.; Sponaas, Anne‐Marit

2016-01-01

Abstract Introduction Mesenchymal stem cells, also called mesenchymal stromal cells, MSCs, have great potential in stem cell therapy partly due to their immunosuppressive properties. How these cells respond to chronic inflammatory stimuli is therefore of importance. Toll‐like receptors (TLR)s are innate immune receptors that mediate inflammatory signals in response to infection, stress, and damage. Caspase‐8 is involved in activation of NF‐kB downstream of TLRs in immune cells. Here we investigated the role of caspase‐8 in regulating TLR‐induced cytokine production from human bone marrow‐derived mesenchymal stromal cells (hBMSCs). Methods Cytokine expression in hBMCs in response to poly(I:C) and LPS was evaluated by PCR, multiplex cytokine assay, and ELISA. TLR3, TRIF, and caspase‐8 were silenced using siRNA. Caspase‐8 was also inhibited using a caspase‐8 inhibitor, z‐IEDT. Results We found that TLR3 agonist poly(I:C) and TLR4 agonist LPS induced secretion of several pro‐inflammatory cytokines in a TLR‐dependent manner which required the TLR signaling adaptor molecule TRIF. Further, poly(I:C) reduced the expression of anti‐inflammatory cytokines HGF and TGFβ whereas LPS reduced HGF expression only. Notably, caspase‐8 was involved in the induction of IL‐ IL‐1β, IL‐6, CXCL10, and in the inhibition of HGF and TGFβ. Conclusion Caspase‐8 appears to modulate hBMSCs into gaining a pro‐inflammatory phenotype. Therefore, inhibiting caspase‐8 in hBMSCs might promote an immunosuppressive phenotype which could be useful in clinical applications to treat inflammatory disorders. PMID:27621815

Cytokines: applications in domestic food animals.

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Blecha, F

1991-01-01

Cytokines such as human, bovine, and porcine interferons and human and bovine interleukin-1 and interleukin-2 have been used in vivo in cattle and pigs. Colony-stimulating factors and tumor necrosis factor alpha have been evaluated in vitro in food animals. Studies to evaluate cytokines in domestic food animals have shown that specific and nonspecific immunomodulation is possible in immunosuppressed or pathogen-exposed animals. Cytokine prophylaxis or therapy in food animals may have the greatest potential for control of respiratory disease and mastitis.

Radiotherapy- and chemotherapy-induced normal tissue damage. The role of cytokines and adhesion molecules

International Nuclear Information System (INIS)

Plevova, P.

2002-01-01

Background. Ionising radiation and cytostatic agents used in cancer therapy exert damaging effects on normal tissues and induce a complex response at the cellular and molecular levels. Cytokines and adhesion molecules are involved in this response. Methods. Published data on the given topic have been reviewed. Results and conclusions. Various cytokines and adhesion molecules, including tumor necrosis factor α, interleukins- 1,-2,-4, and -6, interferon γ, granulocyte macrophage- and macrophage- colony stimulating factors, transforming growth factor β, platelet-derived growth factor, insulin-like growth factor I, fibroblast and epidermal growth factors, platelet-activating factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E- and P-selectins are involved in the response of normal tissues to ionizing radiation- and chemotherapy- induced normal tissues damage and are co-responsible for some side effects of these treatment modalities, including fever, anorexia and fatigue, suppression of hematopoiesis, both acute and late local tissue response. (author)

More inflammation but less brain-derived neurotrophic factor in antisocial personality disorder.

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Wang, Tzu-Yun; Lee, Sheng-Yu; Hu, Ming-Chuan; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chu, Chun-Hsien; Lin, Shih-Hsien; Li, Chia-Ling; Wang, Liang-Jen; Chen, Po See; Chen, Shih-Heng; Huang, San-Yuan; Tzeng, Nian-Sheng; Lee, I Hui; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

2017-11-01

Antisocial personality disorder (ASPD) is highly comorbid with substance use disorders (SUDs). We hypothesize that chronic neuroinflammation and the loss of neurotrophic factors prompts the pathogenesis of both disorders. We used ELISA to measure plasma levels of proinflammatory (tumor necrosis factor-α [TNF-α], C-reactive protein [CRP]) and anti-inflammatory factors (transforming growth factor-β1 [TGF-β1] and interleukin-10 [IL-10]), and brain-derived neurotrophic factor (BDNF) in male patients with ASPD (n=74), SUDs (n=168), ASPD comorbid with SUDs (ASPD+SUDs) (n=438), and Healthy Controls (HCs) (n=81). A multivariate analysis of covariance (MANCOVA) controlled for possible confounders was used to compare cytokines and BDNF levels between groups. The results of MANCOVA adjusted for age showed a significant (pdisorder (OUD) and other SUDs groups showed that the IL-10 levels were specifically higher in OUD and ASPD±OUD groups than other SUDs (P≤0.001). We conclude that uncontrolled inflammation and losing neurotrophic factors, with or without comorbid SUDs, underlies ASPD. IL-10 expression might be more specifically associated with OUD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of poor hygiene on cytokine phenotypes in children in the tropics

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C. A. Figueiredo

2016-11-01

Full Text Available Abstract We describe immune phenotypes (innate and adaptive cytokines according to environmental exposure using latent class analysis. A total of 310 schoolchildren living in Ecuador were assayed for spontaneous cytokine production as well as mitogen (SEB-stimulated cytokines in whole blood cultures. We collected data on environmental exposures by questionnaire and on intestinal parasites by examination of stool samples. Latent class analysis (LCA was used to group children according to their innate (IL-6, IL-8, IL-10 and TNF-α and adaptive (IL-5, IL-13, IL-17, IFN-γ and IL-10 cytokine profile. We also conducted multiple-group LCA and LCA with covariates to evaluate the effect of predictors on profile membership. We identified both hyporesponsive and Th2-modified immune phenotypes produced by peripheral blood leukocytes (PBLs that were associated with intestinal worms and birth order, providing insights into how poor hygiene mediates immunologic effects on immune-mediated diseases.

Effect of soluble factors derived from oral cancer cells on the production of interferon-γ from peripheral blood mononuclear cells following stimulation with OK-432.

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Ohe, Go; Sasai, Akiko; Uchida, Daisuke; Tamatani, Tetsuya; Nagai, Hirokazu; Miyamoto, Youji

2013-08-01

The streptococcal antitumor agent OK-432 is commonly used as an immunopotentiator for immunotherapy in various types of malignant tumors including oral cancer. It has been demonstrated that OK-432 elicits an antitumor effect by stimulating immunocompetent cells, thereby inducing multiple cytokines including interferon (IFN)-γ, interleukin (IL)-2 and IL-12. Serum concentrations of IFN-γ in patients with oral cancer were examined 24 h after administration of OK-432. Serum concentrations of IFN-γ in patients with advanced cancer were significantly lower than those in patients with early cancer. These results suggested that some soluble factors produced by cancer cells may inhibit IFN-γ production with OK-432. Thus, in the present study, an in vitro simulation model was established for the immune status of patients with oral cancer by adding conditioned medium (CM) derived from oral cancer cell lines into a culture of peripheral blood mononuclear cells (PBMCs) derived from a healthy volunteer. We investigated whether soluble factors derived from oral cancer cells affected IFN-γ production from PBMCs following stimulation with OK-432. PBMCs stimulated with OK-432 produced a large amount of IFN-γ; however, both IFN-γ production and cytotoxic activity from PBMCs induced by OK-432 were inhibited by the addition of CM in a dose-dependent manner. In order to examine these inhibitory effects against IFN-γ production, the contribution of inhibitory cytokines such as IL-4, IL-6, IL-10, transforming growth factor-β and vascular endothelial growth factor was investigated. However, neutralization of these inhibitory cytokines did not recover IFN-γ production inhibited by CM. These results indicated that unknown molecules may inhibit IFN-γ production from PBMCs following stimulation with OK-432.

Hematopoietic stem cell cytokines and fibroblast growth factor-2 stimulate human endothelial cell-pericyte tube co-assembly in 3D fibrin matrices under serum-free defined conditions.

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Annie O Smith

Full Text Available We describe a novel 3D fibrin matrix model using recombinant hematopoietic stem cell cytokines under serum-free defined conditions which promotes the assembly of human endothelial cell (EC tubes with co-associated pericytes. Individual ECs and pericytes are randomly mixed together and EC tubes form that is accompanied by pericyte recruitment to the EC tube abluminal surface over a 3-5 day period. These morphogenic processes are stimulated by a combination of the hematopoietic stem cell cytokines, stem cell factor, interleukin-3, stromal derived factor-1α, and Flt-3 ligand which are added in conjunction with fibroblast growth factor (FGF-2 into the fibrin matrix. In contrast, this tube morphogenic response does not occur under serum-free defined conditions when VEGF and FGF-2 are added together in the fibrin matrices. We recently demonstrated that VEGF and FGF-2 are able to prime EC tube morphogenic responses (i.e. added overnight prior to the morphogenic assay to hematopoietic stem cell cytokines in collagen matrices and, interestingly, they also prime EC tube morphogenesis in 3D fibrin matrices. EC-pericyte interactions in 3D fibrin matrices leads to marked vascular basement membrane assembly as demonstrated using immunofluorescence and transmission electron microscopy. Furthermore, we show that hematopoietic stem cell cytokines and pericytes stimulate EC sprouting in fibrin matrices in a manner dependent on the α5β1 integrin. This novel co-culture system, under serum-free defined conditions, allows for a molecular analysis of EC tube assembly, pericyte recruitment and maturation events in a critical ECM environment (i.e. fibrin matrices that regulates angiogenic events in postnatal life.

Pro-inflammatory cytokines derived from West Nile virus (WNV-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death

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Nerurkar Vivek R

2010-10-01

Full Text Available Abstract Background WNV-associated encephalitis (WNVE is characterized by increased production of pro-inflammatory mediators, glial cells activation and eventual loss of neurons. WNV infection of neurons is rapidly progressive and destructive whereas infection of non-neuronal brain cells is limited. However, the role of neurons and pathological consequences of pro-inflammatory cytokines released as a result of WNV infection is unclear. Therefore, the objective of this study was to examine the role of key cytokines secreted by WNV-infected neurons in mediating neuroinflammatory markers and neuronal death. Methods A transformed human neuroblastoma cell line, SK-N-SH, was infected with WNV at multiplicity of infection (MOI-1 and -5, and WNV replication kinetics and expression profile of key pro-inflammatory cytokines were analyzed by plaque assay, qRT-PCR, and ELISA. Cell death was measured in SK-N-SH cell line in the presence and absence of neutralizing antibodies against key pro-inflammatory cytokines using cell viability assay, TUNEL and flow cytometry. Further, naïve primary astrocytes were treated with UV-inactivated supernatant from mock- and WNV-infected SK-N-SH cell line and the activation of astrocytes was measured using flow cytometry and ELISA. Results WNV-infected SK-N-SH cells induced the expression of IL-1β, -6, -8, and TNF-α in a dose- and time-dependent manner, which coincided with increase in virus-induced cell death. Treatment of cells with anti-IL-1β or -TNF-α resulted in significant reduction of the neurotoxic effects of WNV. Furthermore treatment of naïve astrocytes with UV-inactivated supernatant from WNV-infected SK-N-SH cell line increased expression of glial fibrillary acidic protein and key inflammatory cytokines. Conclusion Our results for the first time suggest that neurons are one of the potential sources of pro-inflammatory cytokines in WNV-infected brain and these neuron-derived cytokines contribute to WNV

Parasites of the Giant Panda: A Risk Factor in the Conservation of a Species.

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Wang, Tao; Xie, Yue; Zheng, Youle; Wang, Chengdong; Li, Desheng; Koehler, Anson V; Gasser, Robin B

2018-01-01

The giant panda, with an estimated population size of 2239 in the world (in 2015), is a global symbol of wildlife conservation that is threatened by habitat loss, poor reproduction and limited resistance to some infectious diseases. Of these factors, some diseases caused by parasites are considered as the foremost threat to its conservation. However, there is surprisingly little published information on the parasites of the giant panda, most of which has been disseminated in the Chinese literature. Herein, we review all peer-reviewed publications (in English or Chinese language) and governmental documents for information on parasites of the giant pandas, with an emphasis on the intestinal nematode Baylisascaris schroederi (McIntosh, 1939) as it dominates published literature. The purpose of this chapter is to: (i) review the parasites recorded in the giant panda and describe what is known about their biology; (ii) discuss key aspects of the pathogenesis, diagnosis, treatment and control of key parasites that are reported to cause clinical problems and (iii) conclude by making some suggestions for future research. This chapter shows that we are only just 'scratching the surface' when it comes to parasites and parasitological research of the giant panda. Clearly, there needs to be a concerted research effort to support the conservation of this iconic species. © 2018 Elsevier Ltd All rights reserved.

Prevalence and Risk Factors of Human Intestinal Parasites in Roudehen, Tehran Province, Iran

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Nasrin HEMMATI

2017-09-01

Full Text Available Background: Intestinal parasitic infections are among the most common infections and health problems worldwide. Due to the lack of epidemiologic information of such infections, the prevalence of, and the risk factors for, enteric parasites were investigated in residents of Roudehen, Tehran Province, Iran.Methods: In this cross-sectional study, 561 triple fecal samples were collected through a two-stage cluster-sampling protocol from Jun to Dec 2014. The samples were examined by formalin-ether concentration, culture, and with molecular methods.Results: The prevalence of enteric parasites was 32.7% (95% CI 27.3–38. Blastocystis sp. was the most common intestinal protozoan (28.4%; 95% CI 23.7–33.0. The formalin-ether concentration and culture methods detected Blastocystis sp., Entamoeba coli, Giardia intestinalis, Dientamoeba fragilis, Iodamoeba butschlii, Entamoeba complex cysts or trophozoite, Chilomastix mesnilii, and Enterobius vermicularis. Single-round PCR assay for Entamoeba complex were identified Entamoeba dispar and E. moshkovskii. E. histolytica was not observed in any specimen. Multivariate analysis showed a significant association of parasites with water source and close animal contact. There was no correlation between infections and gender, age, occupation, education, or travel history. Protozoan infections were more common than helminth infections.Conclusion: This study revealed a high prevalence of enteric protozoan parasite infection among citizens of Rodehen. As most of the species detected are transmitted through a water-resistant cyst, public and individual education on personal hygiene should be considered to reduce transmission of intestinal parasites in the population. 

Factor XI Deficiency Alters the Cytokine Response and Activation of Contact Proteases during Polymicrobial Sepsis in Mice.

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Charles E Bane

Full Text Available Sepsis, a systemic inflammatory response to infection, is often accompanied by abnormalities of blood coagulation. Prior work with a mouse model of sepsis induced by cecal ligation and puncture (CLP suggested that the protease factor XIa contributed to disseminated intravascular coagulation (DIC and to the cytokine response during sepsis. We investigated the importance of factor XI to cytokine and coagulation responses during the first 24 hours after CLP. Compared to wild type littermates, factor XI-deficient (FXI-/- mice had a survival advantage after CLP, with smaller increases in plasma levels of TNF-α and IL-10 and delayed IL-1β and IL-6 responses. Plasma levels of serum amyloid P, an acute phase protein, were increased in wild type mice 24 hours post-CLP, but not in FXI-/- mice, supporting the impression of a reduced inflammatory response in the absence of factor XI. Surprisingly, there was little evidence of DIC in mice of either genotype. Plasma levels of the contact factors factor XII and prekallikrein were reduced in WT mice after CLP, consistent with induction of contact activation. However, factor XII and PK levels were not reduced in FXI-/- animals, indicating factor XI deficiency blunted contact activation. Intravenous infusion of polyphosphate into WT mice also induced changes in factor XII, but had much less effect in FXI deficient mice. In vitro analysis revealed that factor XIa activates factor XII, and that this reaction is enhanced by polyanions such polyphosphate and nucleic acids. These data suggest that factor XI deficiency confers a survival advantage in the CLP sepsis model by altering the cytokine response to infection and blunting activation of the contact (kallikrein-kinin system. The findings support the hypothesis that factor XI functions as a bidirectional interface between contact activation and thrombin generation, allowing the two processes to influence each other.

Killing of trypanosomatid parasites by a modified bovine host defense peptide, BMAP-18.

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Lee R Haines

-induced secretion of tumour necrosis factor alpha (TNF-alpha, a cytokine that is associated with inflammation and cachexia (wasting in sleeping sickness patients. As a prelude to in vivo applications, high affinity antibodies to BMAP-18 were produced in rabbits and used in immuno-mass spectrometry assays to detect the intact peptide in human blood and plasma. CONCLUSIONS/SIGNIFICANCE: BMAP-18, a truncated form of the potent antimicrobial BMAP-27, showed low toxicity to mammalian cells, insect cells and the tsetse bacterial symbiont Sodalis glossinidius while retaining an ability to kill a variety of species and life cycle stages of pathogenic kinetoplastid parasites in vitro. BMAP-18 also inhibited secretion of TNF-alpha, an inflammatory cytokine that plays a role in the cachexia associated with African sleeping sickness. These findings support the idea that BMAP-18 should be explored as a candidate for therapy of economically important trypanosome-infected hosts, such as cattle, fish and humans, and for paratransgenic expression in Sodalis glossinidius, a bacterial symbiont in the tsetse vector, as a strategy for interference with trypanosome transmission.

Cytokine Tuning of Intestinal Epithelial Function

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Caroline Andrews

2018-06-01

Full Text Available The intestine serves as both our largest single barrier to the external environment and the host of more immune cells than any other location in our bodies. Separating these potential combatants is a single layer of dynamic epithelium composed of heterogeneous epithelial subtypes, each uniquely adapted to carry out a subset of the intestine’s diverse functions. In addition to its obvious role in digestion, the intestinal epithelium is responsible for a wide array of critical tasks, including maintaining barrier integrity, preventing invasion by microbial commensals and pathogens, and modulating the intestinal immune system. Communication between these epithelial cells and resident immune cells is crucial for maintaining homeostasis and coordinating appropriate responses to disease and can occur through cell-to-cell contact or by the release or recognition of soluble mediators. The objective of this review is to highlight recent literature illuminating how cytokines and chemokines, both those made by and acting on the intestinal epithelium, orchestrate many of the diverse functions of the intestinal epithelium and its interactions with immune cells in health and disease. Areas of focus include cytokine control of intestinal epithelial proliferation, cell death, and barrier permeability. In addition, the modulation of epithelial-derived cytokines and chemokines by factors such as interactions with stromal and immune cells, pathogen and commensal exposure, and diet will be discussed.

Cytokines and uveitis, a review

NARCIS (Netherlands)

de Vos, A. F.; Hoekzema, R.; Kijlstra, A.

1992-01-01

Although the exact pathogenic mechanisms underlying uveitis are unknown, cytokines appear to be involved in this inflammatory disorder. This review describes the studies in which the uveitogenic properties of several cytokines, including tumor necrosis factor (TNF), interleukin 1 (IL-1), IL-6, IL-8

Parasite-specific IL-4 responses in Ascaris suum and Trichuris suis-infected pigs evaluated by ELISPOT

DEFF Research Database (Denmark)

Steenhard, N. R.; Kringel, H.; Roepstorff, A.

2007-01-01

method is a valuable tool for future experimental settings as it enables repeated and parasite-specific measurement of IL-4 at protein level when investigating, for example, immunomodulatory properties of helminths. Furthermore, the method could be used to identify specific parasite antigens inducing IL......The objective of the present study was to develop an ELISPOT method to measure parasite-specific IL-4 producing cells during experimental Ascaris suum and Trichuris suis infections in pigs. In many experimental settings it is useful to be able to measure changes in specifically induced cytokines...

Cytokines and the neurodevelopmental basis of mental illness

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Udani eRatnayake

2013-10-01

Full Text Available Epidemiological studies suggest that prenatal exposure to different types of viral or bacterial infections may be associated with similar outcomes; i.e., an increased risk of mental illness disorders in the offspring. Infections arising from various causes have similar debilitating effects in later life, suggesting that the exact pathogen may not be the critical factor in determining the neurological and cognitive outcome in the offspring. Instead, it is thought that response of the innate immune system, specifically the increased production of inflammatory cytokines, may be the critical mediator in altering fetal brain development pre-disposing the offspring to mental illness disorders later in life. Inflammatory cytokines are essential for normal brain development. Factors such as the site of cytokine production, a change in balance between anti- and pro- inflammatory cytokines, placental transfer of cytokines, the effects of cytokines on glial cells, and the effects of glucocorticoids are important when evaluating the impact of maternal infection on fetal brain development. Although it is clear that cytokines are altered in the fetal brain following maternal infection, further evidence is required to determine if cytokines are the critical factor that alters the trajectory of brain development, subsequently leading to postnatal behavioural and neurological abnormalities.

Leukemia inhibitory factor (LIF) enhances MAP2 + and HUC/D + neurons and influences neurite extension during differentiation of neural progenitors derived from human embryonic stem cells.

Science.gov (United States)

Leukemia Inhibitory Factor (L1F), a member of the Interleukin 6 cytokine family, has a role in differentiation of Human Neural Progenitor (hNP) cells in vitro. hNP cells, derived from Human Embryonic Stem (hES) cells, have an unlimited capacity for self-renewal in monolayer cultu...

Immune response to Taenia solium cysticerci after anti-parasitic therapy.

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Singh, Aloukick K; Singh, Satyendra K; Singh, Amrita; Gupta, Kamlesh K; Khatoon, Jahanarah; Prasad, Amit; Rai, Ravi P; Gupta, Rakesh K; Tripathi, Mukesh; Husain, Nuzhat; Prasad, Kashi N

2015-10-01

Albendazole is the drug of choice for Taenia solium infection. Concomitant administration of steroid has been advocated to avoid adverse reactions to albendazole therapy in neurocysticercosis. Some T. solium cysticerci (larvae) respond to albendazole therapy while others do not and the reasons remain unexplained. We hypothesise that the immune response differs between treatment responder and non-responder cysticerci and this may determine the outcome. Twenty swine naturally infected with T. solium were purchased from the market and the infection was confirmed by magnetic resonance imaging. Swine were divided into two groups; swine in group 1 were treated with albendazole and those in group 2 were treated with albendazole plus steroid (prednisolone). All the animals underwent follow-up MRIs at 6 and 12 weeks after start of therapy and were then sacrificed. Tissues surrounding the cysticerci were collected and studied for the expression of different cytokines by reverse transcriptase PCR and ELISA. Albendazole therapy was found to be more effective in parasite killing than albendazole plus steroid (94.11% versus 70.96%, P=0.011). Albendazole therapy provoked a pro-inflammatory, Th1 (IFN-γ) and pleiotropic (IL-6) cytokine response around the dead cysticerci. Despite a heavy parasite burden in the brain, all the pigs treated with albendazole plus steroid survived. In this group of animals, a mixed pro-inflammatory Th1, Th2 (IL-4) and regulatory cytokine (IL-10) response was associated with responder cysticerci. Further, Th2 and regulatory cytokine responses were associated with non-responder cysticerci. Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Prevalence and Risk Factors of Intestinal Parasite Infection among Schoolchildren in the Peripheral Highland Regions of Huanuco, Peru.

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Choi, Byungjin; Kim, Bongyoung

2017-10-01

Schoolchildren in developing countries are at greater risk of intestinal parasitic infections. This study aimed to estimate the prevalence and assess the risk factors of intestinal parasite infection among schoolchildren in rural areas of Peru. A volunteer team from the Korea International Cooperation Agency (KOICA) conducted a campaign for parasite eradication called "Chao parasitos" at five schools in the peripheral highland regions of Huanuco in October 2013. The study collected questionnaires and stool samples from children of participating schools. Entamoeba coli , Iodamoeba buschii , and Chilomastix mesnil were classified as nonpathogenic parasites. The overall prevalence of intestinal parasite infection in the students was 100% (185/185). Among them, 25.9% (48/185) were infected only with nonpathogenic parasites whereas 74.1% (137/185) were infected with at least one pathogenic parasite. Ascaris lumbricoides was the most commonly detected (37.3%, 69/185), followed by Giardia lamblia (15.1%, 28/185) and I. buschii (11.9%, 22/185). Among lifestyle practices associated with parasitic infection, the rate of washing hands before meals was significantly lower in the students with pathogenic parasites compared to those with nonpathogenic parasites (77.4%, 106/137 vs. 93.8%, 45/48, p = 0.025). The prevalence of intestinal parasite was 100%. Both personal hygiene and water supply facilities are required to eradicate parasite infection in rural areas of Peru.

Brain derived neurotrophic factor

DEFF Research Database (Denmark)

Mitchelmore, Cathy; Gede, Lene

2014-01-01

Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

Associations between socioeconomic factors and proinflammatory cytokines in children, adolescents and young adults: a systematic review protocol.

Science.gov (United States)

Fredman, Nick John; Duque, Gustavo; Duckham, Rachel Louise; Green, Darci; Brennan-Olsen, Sharon Lee

2018-02-28

There is now substantial evidence of a social gradient in bone health. Social stressors, related to socioeconomic status, are suggested to produce an inflammatory response marked by increased levels of proinflammatory cytokines. Here we focus on the particular role in the years before the achievement of peak bone mass, encompassing childhood, adolescence and young adulthood. An examination of such associations will help explain how social factors such as occupation, level of education and income may affect later-life bone disorders. This paper presents the protocol for a systematic review of existing literature regarding associations between socioeconomic factors and proinflammatory cytokines in those aged 6-30 years. We will conduct a systematic search of PubMed, OVID and CINAHL databases to identify articles that examine associations between socioeconomic factors and levels of proinflammatory cytokines, known to influence bone health, during childhood, adolescence or young adulthood. The findings of this review have implications for the equitable development of peak bone mass regardless of socioeconomic factors. Two independent reviewers will determine the eligibility of studies according to predetermined criteria, and studies will be assessed for methodological quality using a published scoring system. Should statistical heterogeneity be non-significant, we will conduct a meta-analysis; however, if heterogeneity prevent numerical syntheses, we will undertake a best-evidence analysis to determine whether socioeconomic differences exist in the levels of proinflammatory cytokines from childhood through to young adulthood. This study will be a systematic review of published data, and thus ethics approval is not required. In addition to peer-reviewed publication, these findings will be presented at professional conferences in national and international arenas. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All

Heterogeneity in cytokine profiles of Babesia bovis-specific bovine CD4+ T cells clones activated in vitro.

OpenAIRE

Brown, W C; Woods, V M; Dobbelaere, D A; Logan, K S

1993-01-01

The central role of T cells in the immune response against hemoprotozoan parasites, both as helper cells for T cell-dependent antibody production and as effector cells acting on intracellular parasites through the elaboration of cytokines, has prompted an investigation of the bovine cellular immune response against Babesia bovis antigens. CD4+ T helper (Th) cell clones generated from four B. bovis-immune cattle by in vitro stimulation with a soluble or membrane-associated merozoite antigen we...

Cytokines, growth, and environment factors in bone marrow plasma of acute lymphoblastic leukemia pediatric patients

Czech Academy of Sciences Publication Activity Database

Kováč, M.; Vášková, M.; Petráčková, Denisa; Pelková, V.; Mejstříková, E.; Kalina, T.; Žaliová, M.

2014-01-01

Roč. 25, č. 1 (2014), s. 8-13 ISSN 1148-5493 R&D Projects: GA MZd NR9531 Institutional support: RVO:61388971 Keywords : pediatric acute lymphoblastic leukemia * bone marrow plasma * cytokine Subject RIV: CE - Biochemistry Impact factor: 1.960, year: 2014

Proteomic analysis of Fasciola hepatica excretory and secretory products (FhESPs) involved in interacting with host PBMCs and cytokines by shotgun LC-MS/MS.

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Liu, Qing; Huang, Si-Yang; Yue, Dong-Mei; Wang, Jin-Lei; Wang, Yujian; Li, Xiangrui; Zhu, Xing-Quan

2017-02-01

Fasciola hepatica is a helminth parasite with a worldwide distribution, which can cause chronic liver disease, fasciolosis, leading to economic losses in the livestock and public health in many countries. Control is mostly reliant on the use of drugs, and as a result, drug resistance has now emerged. The identification of F. hepatica genes involved in interaction between the parasite and host immune system is utmost important to elucidate the evasion mechanisms of the parasite and develop more effective strategies against fasciolosis. In this study, we aimed to identify molecules in F. hepatica excretory and secretory products (FhESPs) interacting with the host peripheral blood mononuclear cells (PBMCs), Th1-like cytokines (IL2 and IFN-γ), and Th17-like cytokines (IL17) by Co-IP combined with tandem mass spectrometry. The results showed that 14, 16, and 9 proteins in FhESPs could bind with IL2, IL17, and IFN-γ, respectively, which indicated that adult F. hepatica may evade the host immune responses through directly interplaying with cytokines. In addition, nine proteins in FhESPs could adhere to PBMCs. Our findings provided potential targets as immuno-regulators, and will be helpful to elucidate the molecular basis of host-parasite interactions and search for new potential proteins as vaccine and drug target candidates.

Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections.

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Sordillo, Peter P; Helson, Lawrence

2015-01-01

The terminal stage of Ebola and other viral diseases is often the onset of a cytokine storm, the massive overproduction of cytokines by the body's immune system. The actions of curcumin in suppressing cytokine release and cytokine storm are discussed. Curcumin blocks cytokine release, most importantly the key pro-inflammatory cytokines, interleukin-1, interleukin-6 and tumor necrosis factor-α. The suppression of cytokine release by curcumin correlates with clinical improvement in experimental models of disease conditions where a cytokine storm plays a significant role in mortality. The use of curcumin should be investigated in patients with Ebola and cytokine storm. Intravenous formulations may allow achievement of therapeutic blood levels of curcumin. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Antibody-cytokine fusion proteins for treatment of cancer: engineering cytokines for improved efficacy and safety.

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Young, Patricia A; Morrison, Sherie L; Timmerman, John M

2014-10-01

The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing interleukin (IL)-2, IL-12, IL-21, tumor necrosis factor (TNF)α, and interferons (IFNs) α, β, and γ have been constructed and have shown anti-tumor activity in preclinical and early-phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results. Copyright © 2014 Elsevier Inc. All rights reserved.

Intestinal parasite infections in immigrant children in the city of Rome, related risk factors and possible impact on nutritional status

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Manganelli Laura

2012-11-01

Full Text Available Abstract Background Parasitic diseases can represent a social and economic problem among disadvantaged people - even in developed countries. Due to the limited data available concerning Europe, the aims of the present study were to evaluate the presence of parasites in immigrant children and the risk factors favouring the spread of parasites. Subsequently, the possible correlation between nutritional status and parasitic infections was also investigated. Findings A convenience sample of two hundred and forty seven immigrant children (aged 0–15 attending the Poliambulatorio della Medicina Solidale in Rome was examined. Data were collected using structured questionnaires, and parasitological and anthropometric tests were applied. Chi-squared test and binary logistic multiple-regression models were used for statistical analysis. Thirty-seven children (15% tested positive to parasites of the following species: Blastocystis hominis, Entamoeba coli, Giardia duodenalis, Enterobius vermicularis, Ascaris lumbricoides and Strongyloides stercoralis. A monospecific infection was detected in 30 (81% out of 37 parasitized children, while the others (19% presented a polyparasitism. The major risk factors were housing, i.e. living in shacks, and cohabitation with other families (p Conclusions This study shows that parasite infection in children is still quite common, even in a developed country and that children’s growth and parasitism may be related. Extensive improvements in the living, social and economic conditions of immigrants are urgently needed in order to overcome these problems.

Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

Science.gov (United States)

Rasuo, Biljana; Hock, Jennifer Vanessa Phi; Kweider, Nisreen; Fragoulis, Athanassios; Sönmez, Tolga Taha; Jahr, Holger; Pufe, Thomas; Lippross, Sebastian

2017-01-01

The etiology and pathogenesis of rheumatoid arthritis (RA) are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP). The main objective of this work is to examine the influences of platelet-released growth factor (PRGF) on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes. PMID:29348703

Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

Directory of Open Access Journals (Sweden)

Mersedeh Tohidnezhad

2017-01-01

Full Text Available The etiology and pathogenesis of rheumatoid arthritis (RA are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP. The main objective of this work is to examine the influences of platelet-released growth factor (PRGF on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes.

Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

International Nuclear Information System (INIS)

Meyer-Siegler, Katherine L; Leifheit, Erica C; Vera, Pedro L

2004-01-01

The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) has previously been associated with various types of adenocarcinoma. MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA), anti-MIF antibody or MIF anti-sense) on cell growth and cytokine expression were analyzed. Human bladder cancer cells (HT-1376) secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44. This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma

Platelet-derived growth factor predicts prolonged relapse-free period in multiple sclerosis.

Science.gov (United States)

Stampanoni Bassi, Mario; Iezzi, Ennio; Marfia, Girolama A; Simonelli, Ilaria; Musella, Alessandra; Mandolesi, Georgia; Fresegna, Diego; Pasqualetti, Patrizio; Furlan, Roberto; Finardi, Annamaria; Mataluni, Giorgia; Landi, Doriana; Gilio, Luana; Centonze, Diego; Buttari, Fabio

2018-04-14

In the early phases of relapsing-remitting multiple sclerosis (RR-MS), a clear correlation between brain lesion load and clinical disability is often lacking, originating the so-called clinico-radiological paradox. Different factors may contribute to such discrepancy. In particular, synaptic plasticity may reduce the clinical expression of brain damage producing enduring enhancement of synaptic strength largely dependent on neurotrophin-induced protein synthesis. Cytokines released by the immune cells during acute inflammation can alter synaptic transmission and plasticity possibly influencing the clinical course of MS. In addition, immune cells may promote brain repair during the post-acute phases, by secreting different growth factors involved in neuronal and oligodendroglial cell survival. Platelet-derived growth factor (PDGF) is a neurotrophic factor that could be particularly involved in clinical recovery. Indeed, PDGF promotes long-term potentiation of synaptic activity in vitro and in MS and could therefore represent a key factor improving the clinical compensation of new brain lesions. The aim of the present study is to explore whether cerebrospinal fluid (CSF) PDGF concentrations at the time of diagnosis may influence the clinical course of RR-MS. At the time of diagnosis, we measured in 100 consecutive early MS patients the CSF concentrations of PDGF, of the main pro- and anti-inflammatory cytokines, and of reliable markers of neuronal damage. Clinical and radiological parameters of disease activity were prospectively collected during follow-up. CSF PDGF levels were positively correlated with prolonged relapse-free survival. Radiological markers of disease activity, biochemical markers of neuronal damage, and clinical parameters of disease progression were instead not influenced by PDGF concentrations. Higher CSF PDGF levels were associated with an anti-inflammatory milieu within the central nervous system. Our results suggest that PDGF could promote a

MicroRNA-302a suppresses influenza A virus-stimulated interferon regulatory factor-5 expression and cytokine storm induction.

Science.gov (United States)

Chen, Xueyuan; Zhou, Li; Peng, Nanfang; Yu, Haisheng; Li, Mengqi; Cao, Zhongying; Lin, Yong; Wang, Xueyu; Li, Qian; Wang, Jun; She, Yinglong; Zhu, Chengliang; Lu, Mengji; Zhu, Ying; Liu, Shi

2017-12-29

During influenza A virus (IAV) infection, cytokine storms play a vital and critical role in clinical outcomes. We have previously reported that microRNA (miR)-302c regulates IAV-induced IFN expression by targeting the 3'-UTR of nuclear factor κB (NF-κB)-inducing kinase. In the current study, we found that miR-302a, another member of the miR-302 cluster, controls the IAV-induced cytokine storm. According to results from cell-based and knockout mouse models, IAV induces a cytokine storm via interferon regulatory factor-5 (IRF-5). We also found that IAV infection up-regulates IRF-5 expression and that IRF-5 in turn promotes IAV replication. Furthermore, we observed that IRF-5 is a direct target of miR-302a, which down-regulated IRF-5 expression by binding its 3'-UTR. Moreover, IAV increased IRF-5 expression by down-regulating miR-302a expression. Interestingly, miR-302a inhibited IAV replication. In IAV-infected patients, miR-302a expression was down-regulated, whereas IRF-5 expression was up-regulated. Taken together, our work uncovers and defines a signaling pathway implicated in an IAV-induced cytokine storm. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Gastrointestinal parasites in Danish goats - prevalence and risk factors

DEFF Research Database (Denmark)

Sörensen, C.; Holm, S. A.; Thamsborg, S. M.

2012-01-01

The aims were to examine prevalence of gastrointestinal parasites in Danish goats, based on faecal examination, in relation to geographical distribution and risk factors, and to investigate the occurrence of anthelmintic resistance in nematodes in selected farms. In April 2012 all Danish goat farms...... with ≥10 female goats (N=132) according to the Central Husbandry Register, were invited to participate. Of these, 25 herds each submitted faecal samples, collected approximately 1 month after turn out, from 4‐12 kids born earlier the same year. During May‐July, a total of 232 samples were examined using...

Intestinal parasitism and socio-environmental factors among Mbyá-Guarani indians, Porto Alegre, Rio Grande do Sul, Brazil

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Clara Lia Costa Brandelli

2012-06-01

Full Text Available Disturbing data reveal the prevalence of intestinal parasites and their relationship with socio-environmental factors among Mbyá-Guarani Indians. The prevalence was determined by spontaneous sedimentation in water, centrifugation-floatation, and Kato-Katz. A socioeconomic questionnaire was submitted to each family. The overall prevalence of intestinal parasites was 88.7%, and 45.5% were polyparasitized. There was 90.5% prevalence of enteric parasites in children (1-12- year-old, and 85% among 13-65-year-old individuals, indicating that both age groups are extensively parasitized. The parasite load was low to moderate for geohelminths and 75% of the families did not have latrine, thus the practice of defecation occurred outdoors. These findings suggest that the multiple intestinal parasitism in the Mbyá-Guarani community is high to the point of being the rule, and that it relates essentially to the traditional lifestyle and health habits. It is urgently necessary to implement the association of anti-parasitic treatment with sanitation improvement. This should be done simultaneously with health education activities for this population.

Intestinal parasitism and socio-environmental factors among Mbyá-Guarani Indians, Porto Alegre, Rio Grande do Sul, Brazil.

Science.gov (United States)

Brandelli, Clara Lia Costa; de Carli, Geraldo Attilio; Macedo, Alexandre José; Tasca, Tiana

2012-01-01

Disturbing data reveal the prevalence of intestinal parasites and their relationship with socio-environmental factors among Mbyá-Guarani Indians. The prevalence was determined by spontaneous sedimentation in water, centrifugation-floatation, and Kato-Katz. A socioeconomic questionnaire was submitted to each family. The overall prevalence of intestinal parasites was 88.7%, and 45.5% were polyparasitized. There was 90.5% prevalence of enteric parasites in children (1-12- year-old), and 85% among 13-65-year-old individuals, indicating that both age groups are extensively parasitized. The parasite load was low to moderate for geohelminths and 75% of the families did not have latrine, thus the practice of defecation occurred outdoors. These findings suggest that the multiple intestinal parasitism in the Mbyá-Guarani community is high to the point of being the rule, and that it relates essentially to the traditional lifestyle and health habits. It is urgently necessary to implement the association of anti-parasitic treatment with sanitation improvement. This should be done simultaneously with health education activities for this population.

The Role of Cytokines, Chemokines, and Growth Factors in the Pathogenesis of Pityriasis Rosea

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Francesco Drago

2015-01-01

Full Text Available Introduction. Pityriasis rosea (PR is an exanthematous disease related to human herpesvirus- (HHV- 6/7 reactivation. The network of mediators involved in recruiting the infiltrating inflammatory cells has never been studied. Object. To investigate the levels of serum cytokines, growth factors, and chemokines in PR and healthy controls in order to elucidate the PR pathogenesis. Materials and Methods. Interleukin- (IL- 1, IL-6, IL-17, interferon- (IFN- γ, tumor necrosis factor- (TNF- α, vascular endothelial growth factor (VEGF, granulocyte colony stimulating factor (G-CSF, and chemokines, CXCL8 (IL-8 and CXCL10 (IP-10, were measured simultaneously by a multiplex assay in early acute PR patients’ sera and healthy controls. Subsequently, sera from PR patients were analysed at 3 different times (0, 15, and 30 days. Results and discussion. Serum levels of IL-17, IFN-γ, VEGF, and IP-10 resulted to be upregulated in PR patients compared to controls. IL-17 has a key role in host defense against pathogens stimulating the release of proinflammatory cytokines/chemokines. IFN-γ has a direct antiviral activity promoting NK cells and virus specific T cells cytotoxicity. VEGF stimulates vasculogenesis and angiogenesis. IP-10 can induce chemotaxis, apoptosis, cell growth, and angiogenesis. Conclusions. Our findings suggest that these inflammatory mediators may modulate PR pathogenesis in synergistic manner.

Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner.

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Vasilopoulou, E; Loubière, L S; Lash, G E; Ohizua, O; McCabe, C J; Franklyn, J A; Kilby, M D; Chan, S Y

2014-06-01

Does triiodothyronine (T3) regulate the secretion of angiogenic growth factors and cytokines by human decidual cells isolated from early pregnancy? T3 modulates the secretion of specific angiogenic growth factors and cytokines, with different regulatory patterns observed amongst various isolated subpopulations of human decidual cells and with a distinct change between the first and second trimesters of pregnancy. Maternal thyroid dysfunction during early pregnancy is associated with complications of malplacentation including miscarriage and pre-eclampsia. T3 regulates the proliferation and apoptosis of fetal-derived trophoblasts, as well as promotes the invasive capability of extravillous trophoblasts (EVT). We hypothesize that T3 may also have a direct impact on human maternal-derived decidual cells, which are known to exert paracrine regulation upon trophoblast behaviour and vascular development at the uteroplacental interface. This laboratory-based study used human decidua from first (8-11 weeks; n = 18) and second (12-16 weeks; n = 12) trimester surgical terminations of apparently uncomplicated pregnancies. Primary cultures of total decidual cells, and immunomagnetic bead-isolated populations of stromal-enriched (CD10+) and stromal-depleted (CD10-) cells, uterine natural killer cells (uNK cells; CD56+) and macrophages (CD14+) were assessed for thyroid hormone receptors and transporters by immunocytochemistry. Each cell population was treated with T3 (0, 1, 10, 100 nM) and assessments were made of cell viability (MTT assay) and angiogenic growth factor and cytokine secretion (immunomediated assay). The effect of decidual cell-conditioned media on EVT invasion through Matrigel(®) was evaluated. Immunocytochemistry showed the expression of thyroid hormone transporters (MCT8, MCT10) and receptors (TRα1, TRβ1) required for thyroid hormone-responsiveness in uNK cells and macrophages from the first trimester. The viability of total decidual cells and the different

The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells.

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Pourgholaminejad, Arash; Aghdami, Nasser; Baharvand, Hossein; Moazzeni, Seyed Mohammad

2016-09-01

Mesenchymal stem cells (MSCs), as cells with potential clinical utilities, have demonstrated preferential incorporation into inflammation sites. Immunophenotype and immunomodulatory functions of MSCs could alter by inflamed-microenvironments due to the local pro-inflammatory cytokine milieu. A major cellular mediator with specific function in promoting inflammation and pathogenicity of autoimmunity are IL-17-producing T helper 17 (Th17) cells that polarize in inflamed sites in the presence of pro-inflammatory cytokines such as Interleukin-1β (IL-1β), IL-6 and IL-23. Since MSCs are promising candidate for cell-based therapeutic strategies in inflammatory and autoimmune diseases, Th17 cell polarizing factors may alter MSCs phenotype and function. In this study, human bone-marrow-derived MSCs (BM-MSC) and adipose tissue-derived MSCs (AD-MSC) were cultured with or without IL-1β, IL-6 and IL-23 as pro-inflammatory cytokines. The surface markers and their differentiation capacity were measured in cytokine-untreated and cytokine-treated MSCs. MSCs-mediated immunomodulation was analyzed by their regulatory effects on mixed lymphocyte reaction (MLR) and the level of IL-10, TGF-β, IL-4, IFN-γ and TNF-α production as immunomodulatory cytokines. Pro-inflammatory cytokines showed no effect on MSCs morphology, immunophenotype and co-stimulatory molecules except up-regulation of CD45. Adipogenic and osteogenic differentiation capacity increased in CD45+ MSCs. Moreover, cytokine-treated MSCs preserved the suppressive ability of allogeneic T cell proliferation and produced higher level of TGF-β and lower level of IL-4. We concluded pro-inflammatory cytokines up-regulate the efficacy of MSCs in cell-based therapy of degenerative, inflammatory and autoimmune disorders. Copyright © 2016. Published by Elsevier Ltd.

Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion.

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Anitua, E; Zalduendo, M M; Prado, R; Alkhraisat, M H; Orive, G

2015-03-01

The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines. © 2014 Wiley Periodicals, Inc.

Inevitability of Genetic Parasites

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Iranzo, Jaime; Puigbò, Pere; Lobkovsky, Alexander E.; Wolf, Yuri I.

2016-01-01

Abstract Almost all cellular life forms are hosts to diverse genetic parasites with various levels of autonomy including plasmids, transposons and viruses. Theoretical modeling of the evolution of primordial replicators indicates that parasites (cheaters) necessarily evolve in such systems and can be kept at bay primarily via compartmentalization. Given the (near) ubiquity, abundance and diversity of genetic parasites, the question becomes pertinent: are such parasites intrinsic to life? At least in prokaryotes, the persistence of parasites is linked to the rate of horizontal gene transfer (HGT). We mathematically derive the threshold value of the minimal transfer rate required for selfish element persistence, depending on the element duplication and loss rates as well as the cost to the host. Estimation of the characteristic gene duplication, loss and transfer rates for transposons, plasmids and virus-related elements in multiple groups of diverse bacteria and archaea indicates that most of these rates are compatible with the long term persistence of parasites. Notably, a small but non-zero rate of HGT is also required for the persistence of non-parasitic genes. We hypothesize that cells cannot tune their horizontal transfer rates to be below the threshold required for parasite persistence without experiencing highly detrimental side-effects. As a lower boundary to the minimum DNA transfer rate that a cell can withstand, we consider the process of genome degradation and mutational meltdown of populations through Muller’s ratchet. A numerical assessment of this hypothesis suggests that microbial populations cannot purge parasites while escaping Muller’s ratchet. Thus, genetic parasites appear to be virtually inevitable in cellular organisms. PMID:27503291

Nitric oxide-releasing agents enhance cytokine-induced tumor necrosis factor synthesis in human mononuclear cells

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Eigler, A; Sinha, B; Endres, S

1993-01-01

In septic shock tumor necrosis factor (TNF) leads to increased nitric oxide (NO) production by induction of NO synthase. An inverse regulatory effect, the influence of NO on cytokine synthesis, has rarely been investigated. The present study assessed the influence of NO-releasing agents on TNF

CD80 and CD86 Costimulatory Molecules Differentially Regulate OT-II CD4+ T Lymphocyte Proliferation and Cytokine Response in Cocultures with Antigen-Presenting Cells Derived from Pregnant and Pseudopregnant Mice

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Tomasz Maj

2014-01-01

Full Text Available Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA were cocultured with CD4+ T cells derived from OT-II mice’s (C57BL6/J-Tg(TcraTcrb1100Mjb/J spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU, activation of these cells (flow cytometry, cytokine profile (ELISA, and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear.

Multiplex Immunoassay of Plasma Cytokine Levels in Men with Alcoholism and the Relationship to Psychiatric Assessments.

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Manzardo, Ann M; Poje, Albert B; Penick, Elizabeth C; Butler, Merlin G

2016-03-29

Chronic alcohol use alters adaptive immunity and cytokine activity influencing immunological and hormone responses, inflammation, and wound healing. Brain cytokine disturbances may impact neurological function, mood, cognition and traits related to alcoholism including impulsiveness. We examined the relationship between plasma cytokine levels and self-rated psychiatric symptoms in 40 adult males (mean age 51 ± 6 years; range 33-58 years) with current alcohol dependence and 30 control males (mean age 48 ± 6 years; range 40-58 years) with no history of alcoholism using multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Log-transformed cytokine levels were analyzed for their relationship with the Symptom Checklist-90R (SCL-90R), Barratt Impulsivity Scales (BIS) and Alcoholism Severity Scale (ASS). Inflammatory cytokines (interferon γ-induced protein-10 (IP-10); monocyte chemoattractant protein-1 (MCP1); regulated on activation, normal T cell expressed and secreted (RANTES)) were significantly elevated in alcoholism compared to controls while bone marrow-derived hematopoietic cytokines and chemokines (granulocyte-colony stimulating factor (GCSF); soluble CD40 ligand (sCD40L); growth-related oncogene (GRO)) were significantly reduced. GRO and RANTES levels were positively correlated with BIS scales; and macrophage-derived chemokine (MDC) levels were positively correlated with SCL-90R scale scores (p alcoholism may influence brain function leading to increased impulsiveness and/or phobia. The novel association between RANTES and GRO and impulsivity phenotype in alcoholism should be further investigated in alcoholism and psychiatric conditions with core impulsivity and anxiety phenotypes lending support for therapeutic intervention.

Assessment of the cytokine profile in peripheral blood mononuclear cells of naturally Sarcoptes scabiei var. canis infested dogs.

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Singh, Shanker K; Dimri, Umesh; Sharma, Bhaskar; Saxena, Meeta; Kumari, Priyambada

2014-12-15

The mechanism of cytokine secretion from T lymphocytes plays an important role in the immune response of dogs and parasitic skin infestations. Assessment of the cytokine profile of naturally S. scabiei var. canis infested dogs could augment understanding of the pathobiology of canine sarcoptic mange. Therefore, the present study examined the cytokines in peripheral blood mononuclear cells of dogs suffering from sarcoptic mange. Thirteen dogs naturally infected with sarcoptic mange participated in the study. The dogs were found positive for S. scabiei var. canis mites in skin scraping examinations and revealed at least three clinical inclusion criteria. Another five clinically healthy dogs were kept as healthy controls. Peripheral blood mononuclear cells were isolated from heparinized blood samples and used for extraction of mRNA. Further, cDNA was synthesized by using 1 mg of mRNA by reverse transcription using oligonucleotide primers. Relative levels of cytokine expression were compared with normalized glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcripts. The levels of interleukin-4, interleukin-5 and transforming growth factor beta (TGF-β) mRNA expression in dogs with sarcoptic mange were significantly higher (P ≤ 0.01), whereas the level of tumor necrosis factor alpha (TNF-α) was significantly lower (P ≤ 0.01) in comparison with the healthy dogs. No remarkable difference was seen for interleukin-2 mRNA expression between these animals. An overproduction IL-4 and IL-5 might be involved in immuno-pathogenesis of canine sarcoptic mange. S. scabiei var. canis mites possibly induce an overproduction of TGF-β and reduced expression of TNF-α and thus could be conferring the immune suppression of infested dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

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Leifheit Erica C

2004-07-01

Full Text Available Abstract Background The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF has previously been associated with various types of adenocarcinoma. Methods MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA, anti-MIF antibody or MIF anti-sense on cell growth and cytokine expression were analyzed. Results Human bladder cancer cells (HT-1376 secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44. Conclusions This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma.

Prevalence and its associated risk factors of intestinal parasitic infections among Yadot primary school children of South Eastern Ethiopia: a cross-sectional study.

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Tulu, Begna; Taye, Solomon; Amsalu, Eden

2014-11-26

Intestinal parasitic infections are posing significant morbidity worldwide. In Ethiopia, due to poor socio-economic status, intestinal parasitic infections are highly prevalent. The main aim of this study was to determine the prevalence of intestinal parasites and its associated risk factors among Yadot primary school children which is found in South-Eastern part of Ethiopia, in the district called Delo-Mena. Institution based cross-sectional study was employed from March to April 2013. In this study, a total of 340 students were selected using simple random sampling, and data on socio-demographic characteristics and factors associated with the prevalence of intestinal parasites as well as stool samples were collected and processed accordingly. Statistical analysis was done using SPSS version 16, and binary and multivariate logistic regression analysis were conducted to measure the strength of association between dependent and independent variables. The overall prevalence of intestinal parasites was 26.2%. Poly-parasitism was detected in 6.2% of the students. Consistently, students who were infected with single, double, triple and quadruple parasites were 20%, 4.7%, 1.2% and 0.3% respectively. In line with this, the most prevalent parasites were Schistosoma mansoni 12.6%, followed by Entamoeba histolytica/dispar 5%, Ascaris lumbricoides 4.7%, and Hymenolepis nana 4.4%. Regarding the risk factors for the infections, not knowing why they wash their hands before meal [(AOR=0.20, 95% CI=0.10-0.40), pintestinal parasitic infections. Intestinal parasitic infections were found to be highly prevalent among Yadot primary school children. Hence, health education, improving sanitation, provision of safe drinking water, increasing latrine use, snail control and deworming to the students are crucial.

Progress of inflammatory cytokines in glaucoma

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Ping Hu

2015-12-01

Full Text Available Glaucomais a group of diseases characterized by optic nerve damage and visual field defect, and pathological high intraocular pressure is a risk factor for glaucoma. Glaucoma is affected by the interaction of multiple genes and environmental factors, and inflammation may be involved in the pathogenesis of glaucoma. A great deal of studies have confirmed that high expression of connective tissue growth factor(CTGF, tumor necrosis factor-α(TNF-α, interleukins(ILs, nuclear factor-kappa B(NF-κBand various cytokines in the aqueous humor of patients with glaucoma, which have a close correlation with pathogenesis of glaucoma.This article reviews the progress of inflammatory cytokines and their relationship with glaucoma.

Prevalence and risk factors of intestinal parasitism among two indigenous sub-ethnic groups in Peninsular Malaysia.

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Chin, Yuee Teng; Lim, Yvonne Ai Lian; Chong, Chun Wie; Teh, Cindy Shuan Ju; Yap, Ivan Kok Seng; Lee, Soo Ching; Tee, Mian Zi; Siow, Vinnie Wei Yin; Chua, Kek Heng

2016-07-18

Intestinal parasitic infections (IPIs) among indigenous people have been widely documented in Malaysia, however, the prevalence of these infections remains high. In the past, most studies have focused on specific species of parasites but polyparasitism has received limited attention. In addition, epidemiology studies on indigenous people tend to consider them as a homogenous group, whereas in reality different sub-ethnic groups have different cultural and living practices. Variations in living habits such as personal hygiene practices may predispose different groups to different parasitic infections. To better understand prevalence and risk factors of intestinal parasitism among different sub-ethnic groups, the present study was conducted among two sub-ethnic groups of indigenous people (Temuan and Mah Meri) residing in Selangor state, Malaysia. A cross-sectional study that focused on two distinct sub-ethnic groups was carried out from February to September 2014. Faecal samples were collected from 186 participants and examined using the formalin-ether sedimentation technique. A molecular approach was adopted to conduct a genetic characterisation of the parasites. Additionally, questionnaires were administered to obtain information on the demographics, socio-economic backgrounds and behavioural risks relating to the participants, as well as information about their environments. Statistical analyses (i.e. binary and multivariate logistic regression analyses) were performed to measure risk factors. For Temuan communities, trichuriasis (64.2 %) was the most common infection found, preceding hookworm infection (34 %), ascariasis (7.5 %), giardiasis (14.2 %) and amoebiasis (7.5 %). As for the Mah Meri communities, trichuriasis (77.5 %) prevailed over ascariasis (21.3 %), hookworm (15 %), giardiasis (7.5 %) and amoebiasis (3.8 %). Significant differences in proportions of trichuriasis, ascariasis and hookworm infections were observed between the Temuan and Mah

(macro- Evolutionary ecology of parasite diversity: From determinants of parasite species richness to host diversification

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Serge Morand

2015-04-01

Full Text Available The present review summarized the factors or determinants that may explain parasite diversity among host species and the consequences of this parasite diversity on the evolution of host-life history traits. As host–parasite interactions are asymmetrical exploited–exploiter relationships, ecological and epidemiological theories produce hypotheses to find the potential determinants of parasite species richness, while life-history theory helps for testing potential consequences on parasite diversity on the evolution of hosts. This review referred only to studies that have specifically controlled or took into account phylogenetic information illustrated with parasites of mammals. Several points needing more investigation were identified with a special emphasis to develop the metabolic theory of epidemiology.

From Parasite Encounter to Infection: Multiple-Scale Drivers of Parasite Richness in a Wild Social Primate Population

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Benavides J. A.; Huchard, E.; Pettorelli, N.; King, A. J.; Brown, M. E.; Archer, C. E.; Appleton, C. C.; Raymond, M.; Cowlishaw, G.

2011-01-01

Host parasite diversity plays a fundamental role in ecological and evolutionary processes, yet the factors that drive it are still poorly understood. A variety of processes, operating across a range of spatial scales, are likely to influence both the probability of parasite encounter and subsequent infection. Here, we explored eight possible determinants of parasite richness, comprising rainfall and temperature at the population level, ranging behavior and home range productivity at the group level, and age, sex, body condition, and social rank at the individual level. We used a unique dataset describing gastrointestinal parasites in a terrestrial subtropical vertebrate (chacma baboons, Papio ursinus), comprising 662 faecal samples from 86 individuals representing all age-sex classes across two groups over two dry seasons in a desert population. Three mixed models were used to identify the most important factor at each of the three spatial scales (population, group, individual); these were then standardised and combined in a single, global, mixed model. Individual age had the strongest influence on parasite richness, in a convex relationship. Parasite richness was also higher in females and animals in poor condition, albeit at a lower order of magnitude than age. Finally, with a further halving of effect size, parasite richness was positively correlated to day range and temperature. These findings indicate that a range of factors influence host parasite richness through both encounter and infection probabilities, but that individual-level processes may be more important than those at the group or population level.

Cytokine gene expression profiles in chicken spleen and intestinal tissues during Ascaridia galli infection

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Pleidrup, Janne A.; Norup, Liselotte R.; Dalgaard, Tina S.

2014-01-01

In the poultry production industry, chickens with access to outdoor areas are exposed to a wide range of parasites e.g. the helminth Ascaridia galli. By real-time quantitative RTPCR, the relative gene expression of the T helper 1 (Th1) cytokine IFN-gamma, the T helper 2 (Th2) cytokine IL-13...... expression of jejunal IFN-gamma and IL-13 was observed. Finally, at the expected period of an adaptive immune response (days 14-21) a general decreased expression of IFN-gamma and TGF-beta 4 in spleen and IFN-gamma in jejunum was followed by a decreased expression of IFN-gamma and IL-10 at day 21 in caecal...

Effects of CD14 macrophages and proinflammatory cytokines on chondrogenesis in osteoarthritic synovium-derived stem cells.

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Han, Sun Ae; Lee, Sahnghoon; Seong, Sang Cheol; Lee, Myung Chul

2014-10-01

We investigated the effects of CD14 macrophages and proinflammatory cytokines on chondrogenic differentiation of osteoarthritic synovium-derived stem cells (SDSCs). Osteoarthritic synovial fluid was analyzed for interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6. Levels of stem cell surface markers in osteoarthritic SDSCs were evaluated using flow cytometry. CD14-negative cells were obtained using magnetically activated cell sorting. We compared chondrogenic potentials between whole cells and CD14-negative cells in CD14(low) cells and CD14(high) cells, respectively. To assess whether nuclear factor-κB (NF-κB) and CCAAT/enhancer-binding protein β (C/EBPβ) modulate IL-1β-induced alterations in chondrogenic potential, we performed small interfering RNA transfection. We observed a significant correlation between the CD14 ratio in osteoarthritic SDSCs and IL-1β and TNF-α in osteoarthritic synovial fluid. Phenotypic characterization of whole cells and CD14-negative cells showed no significant differences in levels of stem cell markers. mRNA expression of type II collagen was higher in CD14-negative cell pellets than in whole cell pellets. Immunohistochemical staining indicated higher levels of type II collagen in the CD14-negative cell pellets of CD14(high) cells than in whole cell pellets of CD14(high) cells. As expected, IL-1β and TNF-α significantly inhibited the expression of chondrogenic-related genes in SDSCs, an effect which was antagonized by knockdown of NF-κB and C/EBPβ. Our results suggest that depletion of CD14(+) synovial macrophages leads to improved chondrogenic potential in CD14(high) cell populations in osteoarthritic SDSCs, and that NF-κB (RelA) and C/EBPβ are critical factors mediating IL-1β-induced suppression of the chondrogenic potential of human SDSCs.

Growth Modeling of the Maternal Cytokine Milieu throughout Normal Pregnancy: Macrophage-Derived Chemokine Decreases as Inflammation/Counterregulation Increases

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Shernan G. Holtan

2015-01-01

Full Text Available Several recent studies have shown differences in the maternal immune milieu at different phases of pregnancy, but most studies have been cross-sectional or of relatively few time points. Levels of 42 cytokines were determined using a multiplex bead-based assay on archived serum from a cohort of pregnant women N=16 at median of 18 time points tested, from the first trimester through to parturition, per woman. Unconditional growth modeling was then used to determine time-dependent changes in levels of these cytokines. Macrophage-derived chemokine (MDC, aka CCL22 decreases as pregnancy progresses. IL-1β, IL-6, IL-8, IL-12p70, IL-13, IL-15, IP-10, and FLT3-ligand increase as a function of gestational weeks, and IFNα2, IL-1ra, IL-3, IL-9, IL-12p40, and soluble CD40 ligand increase as a function of trimester. As pregnancy normally progresses, a maternal shift away from a type 2-biased immune response and toward an inflammatory/counterregulatory response is observed.

Differential cytokine contributions of perivascular haematopoietic stem cell niches.

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Asada, Noboru; Kunisaki, Yuya; Pierce, Halley; Wang, Zichen; Fernandez, Nicolas F; Birbrair, Alexander; Ma'ayan, Avi; Frenette, Paul S

2017-03-01

Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor (Scf) from all perivascular cells marked by nestin-GFP dramatically depleted BM HSCs. Selective Cxcl12 deletion from arteriolar NG2 + cells, but not from sinusoidal LepR + cells, caused HSC reductions and altered HSC localization in BM. By contrast, deletion of Scf in LepR + cells, but not NG2 + cells, led to reductions in BM HSC numbers. These results uncover distinct contributions of cytokines derived from perivascular cells in separate vascular niches to HSC maintenance.

Cytokines in human milk.

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Garofalo, Roberto

2010-02-01

Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

Cross-Sectional Study on the Prevalence of Intestinal Parasites and Associated Risk Factors in Teda Health Centre, Northwest Ethiopia.

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Abate, Abraraw; Kibret, Biniam; Bekalu, Eylachew; Abera, Sendeku; Teklu, Takele; Yalew, Aregawi; Endris, Mengistu; Worku, Ligabaw; Tekeste, Zinaye

2013-01-01

Objective. To assess the magnitude of intestinal parasitic infection and associated risk factors in Teda Health Centre, Northwest Ethiopia. Method. A cross-sectional study was conducted in Teda Health Centre from February to April, 2011. Stool samples were collected from 410 study participants and analysed by direct wet mount and formal ether concentration techniques. Furthermore, sociodemographic data were collected by using standardized questionnaire. Result. The overall prevalence of intestinal parasitic infection in this study was 62.3%. Ascaris lumbricoides was the most predominant parasite (23.2%) followed by Giardia intestinalis (12.4%), Entamoeba histolytica/dispar (4.6%), Schistosoma mansoni (8.9%), hookworm (6.6%), Hymenolepis nana (1.5%), Enterobius vermicularis (0.4%), and Strongyloides stercoralis (0.2%). Absence of toilet and hand washing after toilet was shown to be associated with intestinal parasitic infection (P intestinal parasitic infection in the study area. Absence of toilet and hand washing after toilet was found to be associated with intestinal parasitic infection. Therefore, there is a need for integrated control programme to have a lasting impact on transmission of intestinal parasitic infection.

CYTOKINES GENETIC POLYMORPHISM: THE PAST AND THE FUTURE

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L. V. Puzyryova

2016-01-01

Full Text Available The molecular genetics opens the new horizons in modern medicine, especially now when many diseases are given huge value in a type of their prevalence among various groups of population. Extremely high interleukin genes polymorphism degrees are studied well especially genetic polymorphism of tumor necrosis factor. Patients with HIV infection in the territory of Russia cause now the highest degree of mortality that is the most actual and socially significant problem of healthcare. This problems studying attracts many researchers. Works in respect of genetic immunity to a virus and influence of cytokines production on the disease forecast are especially interesting. One of the HIV replication influencing factors are cytokines, some of which, including the tumor necrosis factor and interleukin-6 can promote replication of HIV, raising an expression of virus regulatory genes. During disease progress in parallel of anti-inflammatory cytokines level increase (causing in this case rather ineffective antibodies level increase there is an T-helpers suppression stimulating a strong cellular component. Cytokine network functioning during HIV infection depends on many reasons which the individual variation in cytokine production caused by a number of genetic features, as well as an existence of opportunistic infection. Cytokines polymorphism determination in HIV infected patients is necessary in clinical practice for disease progression forecast to adverse fast transition to AIDS that it is important to consider in a choice of tactics of the supporting therapy of HIV-positive patients. Considering insufficient efficiency of modern methods of treatment, restoration and modulation of cytokines balance will increase anti-virus activity of immune system, influencing the factors blocking replication of a HIV.

Innate Lymphoid Cells (ILCs): Cytokine Hubs Regulating Immunity and Tissue Homeostasis

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Nagasawa, Maho; Spits, Hergen; Ros, Xavier Romero

2017-01-01

Innate lymphoid cells (ILCs) have emerged as an expanding family of effector cells particularly enriched in the mucosal barriers. ILCs are promptly activated by stress signals and multiple epithelial- and myeloid-cell-derived cytokines. In response, ILCs rapidly secrete effector cytokines, which

Circulating cytokines and cytokine receptors in infliximab treatment failure due to TNF-α independent Crohn disease

DEFF Research Database (Denmark)

Steenholdt, Casper; Coskun, Mehmet; Buhl, Sine

2016-01-01

-IFX antibodies. Circulating cytokines and cytokine receptors were assessed by enzyme-linked immunosorbent assay: granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1α, IL-1β, IL-1Ra, IL-6, IL-10, IL-12p70, soluble TNF receptor (sTNF-R) 1, sTNF-R2, IL-17A, and monocyte chemotactic...

The strigolactone germination stimulants of the plant-parasitic Striga and Orobanche spp. are derived from the carotenoid pathway.

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Matusova, Radoslava; Rani, Kumkum; Verstappen, Francel W A; Franssen, Maurice C R; Beale, Michael H; Bouwmeester, Harro J

2005-10-01

The seeds of parasitic plants of the genera Striga and Orobanche will only germinate after induction by a chemical signal exuded from the roots of their host. Up to now, several of these germination stimulants have been isolated and identified in the root exudates of a series of host plants of both Orobanche and Striga spp. In most cases, the compounds were shown to be isoprenoid and belong to one chemical class, collectively called the strigolactones, and suggested by many authors to be sesquiterpene lactones. However, this classification was never proven; hence, the biosynthetic pathways of the germination stimulants are unknown. We have used carotenoid mutants of maize (Zea mays) and inhibitors of isoprenoid pathways on maize, cowpea (Vigna unguiculata), and sorghum (Sorghum bicolor) and assessed the effects on the root exudate-induced germination of Striga hermonthica and Orobanche crenata. Here, we show that for these three host and two parasitic plant species, the strigolactone germination stimulants are derived from the carotenoid pathway. Furthermore, we hypothesize how the germination stimulants are formed. We also discuss this finding as an explanation for some phenomena that have been observed for the host-parasitic plant interaction, such as the effect of mycorrhiza on S. hermonthica infestation.

Prevalence of intestinal parasitic infections and associated risk factors among students at Dona Berber primary school, Bahir Dar, Ethiopia.

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Hailegebriel, Tamirat

2017-05-23

Intestinal parasitic infections are still one of the major health concerns in developing countries. Monitoring of intestinal parasitic infection and associated risk factors are essential for intervention strategies. Therefore, the aim of this study was to assess the prevalence of intestinal parasitic infection and associated risk factors among students at Dona Berber primary school, Bahir Dar, Ethiopia. School based cross-sectional study was conducted among students at Dona Berber primary school from October 2015 to June 2016. Three hundred fifty nine students were involved in the study by providing stool specimens and detailed personal information. Students were selected by stratified and systematic random sampling method. Fresh stool samples were collected from each student and processed by formal-ether fecal concentration technique. Data were analyzed using SPSS version 20.0 statistical software and p value intestinal parasites. The rates of single and double parasitic infections among students were 49.6% and 16.2%, respectively. The most prevalent parasite detected in the study was E. histolytica/dispar (24.5%) followed by hookworm (22.8%). Among the different variables assessed in the study, family size of 6 (AOR = 4.90; 95% CI, 2.03-11.83), irregularly shoe wearing habit (AOR = 2.85; 95% CI, 1.53-5.32) and unclean finger nail (AOR = 3.68; 95% CI, 1.87-7.26) were independently predict intestinal parasitic infections. Student drinking well water (AOR = 2.51; 95% CI, 2.30-4.86) and unclean finger nail (AOR = 4.42; 95% CI, 2.55-7.65) were strongly associated with E. histolytica/dispar infection. Likewise, irregular shoe wearing habit (AOR = 14.13; 95% CI, 7.06-28.29) was strongly associated with hookworm infections. High prevalence of intestinal parasitic infection among the study participants demands improvement of health education, environmental sanitation and quality of water sources.

Regulation of human cytokines by Cordyceps militaris

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Yong Sun

2014-12-01

Full Text Available Cordyceps (Cordyceps militaris exhibits many biological activities including antioxidant, inhibition of inflammation, cancer prevention, hypoglycemic, and antiaging properties, etc. However, a majority of studies involving C. militaris have focused only on in vitro and animal models, and there is a lack of direct translation and application of study results to clinical practice (e.g., health benefits. In this study, we investigated the regulatory effects of C. militaris micron powder (3 doses on the human immune system. The study results showed that administration of C. militaris at various dosages reduced the activity of cytokines such as eotaxin, fibroblast growth factor-2, GRO, and monocyte chemoattractant protein-1. In addition, there was a significant decrease in the activity of various cytokines, including GRO, sCD40L, and tumor necrosis factor-α, and a significant downregulation of interleukin-12(p70, interferon-γ inducible protein 10, and macrophage inflammatory protein-1β activities, indicating that C. militaris at all three dosages downregulated the activity of cytokines, especially inflammatory cytokines and chemokines. Different dosages of C. militaris produced different changes in cytokines.

Hepatocyte growth factor modulates interleukin-6 production in bone marrow derived macrophages: implications for inflammatory mediated diseases.

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Gina M Coudriet

2010-11-01

Full Text Available The generation of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β fuel the acute phase response (APR. To maintain body homeostasis, the increase of inflammatory proteins is resolved by acute phase proteins via presently unknown mechanisms. Hepatocyte growth factor (HGF is transcribed in response to IL-6. Since IL-6 production promotes the generation of HGF and induces the APR, we posited that accumulating HGF might be a likely candidate for quelling excess inflammation under non-pathological conditions. We sought to assess the role of HGF and how it influences the regulation of inflammation utilizing a well-defined model of inflammatory activation, lipopolysaccharide (LPS-stimulation of bone marrow derived macrophages (BMM. BMM were isolated from C57BL6 mice and were stimulated with LPS in the presence or absence of HGF. When HGF was present, there was a decrease in production of the pro-inflammatory cytokine IL-6, along with an increase in the anti-inflammatory cytokine IL-10. Altered cytokine production correlated with an increase in phosphorylated GSK3β, increased retention of the phosphorylated NFκB p65 subunit in the cytoplasm, and an enhanced interaction between CBP and phospho-CREB. These changes were a direct result of signaling through the HGF receptor, MET, as effects were reversed in the presence of a selective inhibitor of MET (SU11274 or when using BMM from macrophage-specific conditional MET knockout mice. Combined, these data provide compelling evidence that under normal circumstances, HGF acts to suppress the inflammatory response.

Protein moonlighting in parasitic protists.

Science.gov (United States)

Ginger, Michael L

2014-12-01

Reductive evolution during the adaptation to obligate parasitism and expansions of gene families encoding virulence factors are characteristics evident to greater or lesser degrees in all parasitic protists studied to date. Large evolutionary distances separate many parasitic protists from the yeast and animal models upon which classic views of eukaryotic biochemistry are often based. Thus a combination of evolutionary divergence, niche adaptation and reductive evolution means the biochemistry of parasitic protists is often very different from their hosts and to other eukaryotes generally, making parasites intriguing subjects for those interested in the phenomenon of moonlighting proteins. In common with other organisms, the contribution of protein moonlighting to parasite biology is only just emerging, and it is not without controversy. Here, an overview of recently identified moonlighting proteins in parasitic protists is provided, together with discussion of some of the controversies.

Cytokine induction of sol–gel-derived TiO2 and SiO2 coatings on metallic substrates after implantation to rat femur

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Urbanski, Wiktor; Marycz, Krzysztof; Krzak, Justyna; Pezowicz, Celina; Dragan, Szymon Feliks

2017-01-01

Material surface is a key determinant of host response on implanted biomaterial. Therefore, modification of the implant surface may optimize implant–tissue reactions. Inflammatory reaction is inevitable after biomaterial implantation, but prolonged inflammation may lead to adverse reactions and subsequent implant failure. Proinflammatory activities of cytokines like interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) are attractive indicators of these processes and ultimately characterize biocompatibility. The objective of the study was to evaluate local cytokine production after implantation of stainless steel 316L (SS) and titanium alloy (Ti6Al4V) biomaterials coated with titanium dioxide (TiO2) and silica (SiO2) coatings prepared by sol–gel method. Biomaterials were implanted into rat femur and after 12 weeks, bones were harvested. Bone–implant tissue interface was evaluated; immunohistochemical staining was performed to identify IL-6, TNF-α, and Caspase-1. Histomorphometry (AxioVision Rel. 4.6.3 software) of tissue samples was performed in order to quantify the cytokine levels. Both the oxide coatings on SS and Ti6Al4V significantly reduced cytokine production. However, the lowest cytokine levels were observed in TiO2 groups. Cytokine content in uncoated groups was lower in Ti6Al4V than in SS, although coating of either metal reduced cytokine production to similar levels. Sol–gel TiO2 or SiO2 coatings reduced significantly the production of proinflammatory cytokines by local tissues, irrespective of the material used as a substrate, that is, either Ti6Al4V or SS. This suggests lower inflammatory response, which directly points out improvement of materials’ biocompatibility. PMID:28280331

Intestinal parasitic infections: Current prevalence and risk factors among schoolchildren in capital area of the Republic of Marshall Islands.

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Liao, Chien-Wei; Chuang, Ting-Wu; Huang, Ying-Chieh; Chou, Chia-Mei; Chiang, Chia-Lien; Lee, Fei-Peng; Hsu, Yun-Ting; Lin, Jia-Wei; Briand, Kennar; Tu, Chia-Ying; Fan, Chia-Kwung

2017-12-01

Intestinal parasitic infections (IPIs) among schoolchildren in Republic of Marshall Islands (RMI) largely remains unknown, thus investigation on IPIs status to establish the baseline data is urgently needed. This cross-sectional study intended to investigate the current IPIs status and associated risk factors among schoolchildren at capital of RMI. Single stool sample from 400 schoolchildren (207 boys and 193 girls) aged 9.73±2.50 yrs old was examined by employing merthiolate-iodine-formaldehyde concentration method. Demographic characteristics, uncomfortable symptoms and risk factors were obtained by questionnaires investigation. The overall prevalence of IPIs in schoolchildren was 22.8% (91/400), of them 24.2% harbored at least 2 different parasites. Notably, the majority was infected by waterborne protozoan parasites (82.4%, 75/91). Nine different intestinal parasites have been identified, of which six were pathogenic including Hook worm, Trichuris trichiura, Enterobius vermicularis, Entamoeba histolytica/dispar, Giardia intestinalis and Blastocystis hominis. Schoolchildren who ever complained dizziness or headache showed a significant higher prevalence of pathogenic IPIs than those who did not (p<0.05). Schoolchildren who lived in urban area than rural area had higher chance to acquire pathogenic IPIs (p=0.03). However, none of risk factors were identified to be associated with pathogenic IPIs. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of parasites on wildlife

NARCIS (Netherlands)

Borgsteede, F.H.M.

1996-01-01

Populations of animals which live in the wild are regulated by many biotic and abiotic factors. Parasites are one of the biotic factors. Parasites may influence their hosts in different ways. They may cause the death of the host due to a direct lethal effect or an indirect effect. Direct lethal

Brood parasitism and quasi-parasitism in the European barn swallow Hirundo rustica rustica

Czech Academy of Sciences Publication Activity Database

Petrželková, Adéla; Michálková, R.; Albrechtová, Jana; Cepák, J.; Honza, Marcel; Kreisinger, J.; Munclinger, P.; Soudková, M.; Tomášek, Oldřich; Albrecht, Tomáš

2015-01-01

Roč. 69, č. 9 (2015), s. 1405-1414 ISSN 0340-5443 R&D Projects: GA ČR(CZ) GAP506/12/2472 Institutional support: RVO:68081766 Keywords : Altricial birds * Colonial breeding * Conspecific brood parasitism * Egg dumping * Host fitness * Parasite fitness Subject RIV: EG - Zoology Impact factor: 2.382, year: 2015

Cytokine signalling in embryonic stem cells

DEFF Research Database (Denmark)

Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis

2006-01-01

Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...

Cytokine production in BALB/c mice immunized with radiation attenuated third stage larvae of the filarial nematode, Brugia pahangi

International Nuclear Information System (INIS)

Bancroft, A.J.; Devaney, E.; Grencis, R.K.; Else, K.J.

1993-01-01

BALB/c mice immunized with radiation-attenuated third stage larvae of the filarial nematode Brugia pahangi are strongly immune to challenge infection. Investigation of the profile of cytokines secreted by spleen cells from immune mice stimulated in vitro with either parasite Ag or with Con A revealed high levels of IL-5 and IL-9 and moderate levels of IL-4. In contrast, secretion of IFN-γ by spleen cells from immune animals was negligible. Spleen cells from control mice secreted low levels of all cytokines assayed. Levels of parasite-specific IgE were significantly elevated in immune animals and a peripheral blood eosinophilia was observed, which exhibited a biphasic distribution. Our results are consistent with the preferential expansion of Th2 cells in immune animals and provide the basis for dissecting the means by which radiation-attenuated larvae of filarial nematodes stimulate immunity. 5l refs., 3 figs., 3 tabs

Circulating Red Cell–derived Microparticles in Human Malaria

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Nantakomol, Duangdao; Dondorp, Arjen M.; Krudsood, Srivicha; Udomsangpetch, Rachanee; Pattanapanyasat, Kovit; Combes, Valery; Grau, Georges E.; White, Nicholas J.; Viriyavejakul, Parnpen; Day, Nicholas P.J.

2011-01-01

In patients with falciparum malaria, plasma concentrations of cell-derived microparticles correlate with disease severity. Using flow cytometry, we quantified red blood cell–derived microparticles (RMPs) in patients with malaria and identified the source and the factors associated with production. RMP concentrations were increased in patients with Plasmodium falciparum (n = 29; median, 457 RMPs/μL [range, 13–4,342 RMPs/μL]), Plasmodium vivax (n = 5; median, 409 RMPs/μL [range, 281–503/μL]), and Plasmodium malariae (n = 2; median, 163 RMPs/μL [range, 127–200 RMPs/μL]) compared with those in healthy subjects (n = 11; median, 8 RMPs/μL [range, 3–166 RMPs/μL]; P = .01). RMP concentrations were highest in patients with severe falciparum malaria (P = .01). Parasitized red cells produced >10 times more RMPs than did unparasitized cells, but the overall majority of RMPs still derived from uninfected red blood cells (URBCs). In cultures, RMP production increased as the parasites matured. Hemin and parasite products induced RMP production in URBCs, which was inhibited by N-acetylcysteine, suggesting heme-mediated oxidative stress as a pathway for the generation of RMPs. PMID:21282195

Circulating red cell-derived microparticles in human malaria.

Science.gov (United States)

Nantakomol, Duangdao; Dondorp, Arjen M; Krudsood, Srivicha; Udomsangpetch, Rachanee; Pattanapanyasat, Kovit; Combes, Valery; Grau, Georges E; White, Nicholas J; Viriyavejakul, Parnpen; Day, Nicholas P J; Chotivanich, Kesinee

2011-03-01

In patients with falciparum malaria, plasma concentrations of cell-derived microparticles correlate with disease severity. Using flow cytometry, we quantified red blood cell-derived microparticles (RMPs) in patients with malaria and identified the source and the factors associated with production. RMP concentrations were increased in patients with Plasmodium falciparum (n = 29; median, 457 RMPs/μL [range, 13-4,342 RMPs/μL]), Plasmodium vivax (n = 5; median, 409 RMPs/μL [range, 281-503/μL]), and Plasmodium malariae (n = 2; median, 163 RMPs/μL [range, 127-200 RMPs/μL]) compared with those in healthy subjects (n = 11; median, 8 RMPs/μL [range, 3-166 RMPs/μL]; P = .01). RMP concentrations were highest in patients with severe falciparum malaria (P = .01). Parasitized red cells produced >10 times more RMPs than did unparasitized cells, but the overall majority of RMPs still derived from uninfected red blood cells (URBCs). In cultures, RMP production increased as the parasites matured. Hemin and parasite products induced RMP production in URBCs, which was inhibited by N-acetylcysteine, suggesting heme-mediated oxidative stress as a pathway for the generation of RMPs.

Brain-derived neurotrophic factor and interleukin-6 levels in the serum and cerebrospinal fluid of children with viral infection-induced encephalopathy.

Science.gov (United States)

Morichi, Shinichiro; Yamanaka, Gaku; Ishida, Yu; Oana, Shingo; Kashiwagi, Yasuyo; Kawashima, Hisashi

2014-11-01

We investigated changes in the brain-derived neurotrophic factor (BDNF) and interleukin (IL)-6 levels in pediatric patients with central nervous system (CNS) infections, particularly viral infection-induced encephalopathy. Over a 5-year study period, 24 children hospitalized with encephalopathy were grouped based on their acute encephalopathy type (the excitotoxicity, cytokine storm, and metabolic error types). Children without CNS infections served as controls. In serum and cerebrospinal fluid (CSF) samples, BDNF and IL-6 levels were increased in all encephalopathy groups, and significant increases were noted in the influenza-associated and cytokine storm encephalopathy groups. Children with sequelae showed higher BDNF and IL-6 levels than those without sequelae. In pediatric patients, changes in serum and CSF BDNF and IL-6 levels may serve as a prognostic index of CNS infections, particularly for the diagnosis of encephalopathy and differentiation of encephalopathy types.

Effects of wetland vs. landscape variables on parasite communities of Rana pipiens: links to anthropogenic factors

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Schotthoefer, Anna M.; Rohr, Jason R.; Cole, Rebecca A.; Koehler, Anson V.; Johnson, Catherine M.; Johnson, Lucinda B.; Beasley, Val R.

2011-01-01

The emergence of several diseases affecting amphibian populations worldwide has prompted investigations into determinants of the occurrence and abundance of parasites in frogs. To understand the spatial scales and identify specific environmental factors that determine risks of parasitism in frogs, helminth communities in metamorphic frogs of the northern leopard frog (Rana pipiens) were examined in relation to wetland and landscape factors at local (1 km) and regional (10 km) spatial extents in an agricultural region of Minnesota (USA) using regression analyses, ordination, and variance partitioning techniques. Greater amounts of forested and woody wetland habitats, shorter distances between woody wetlands, and smaller-sized open water patches in surrounding landscapes were the most consistently positive correlates with the abundances, richness, and diversity of helminths found in the frogs. Wetland and local landscape variables were suggested as most important for larval trematode abundances, whereas local and regional landscape variables appeared most important for adult helminths. As previously reported, the sum concentration of atrazine and its metabolite desethylatrazine, was the strongest predictor of larval trematode communities. In this report, we highlight the additional influences of landscape factors. In particular, our data suggest that anthropogenic activities that have resulted in the loss of the availability and connectivity of suitable habitats in the surrounding landscapes of wetlands are associated with declines in helminth richness and abundance, but that alteration of wetland water quality through eutrophication or pesticide contamination may facilitate the transmission of certain parasite taxa when they are present at wetlands. Although additional research is needed to quantify the negative effects of parasitism on frog populations, efforts to reduce inputs of agrochemicals into wetlands to limit larval trematode infections may be warranted

FACTORS OF RISK TO INTESTINAL PARASITE INFECTIONS AMONG PUBLIC SHOOLCHILDEN IN BAHIA

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Camila Pereira

2014-08-01

Full Text Available This research was the aim of studying the prevalence of intestinal parasites in school children of the one public school on the periphery of the city of Jequié-BA, and the factors keys involved in the epidemiology of enteroparasites. They were analyzed fecal samples by the sedimentation technique. They obtained data on personal and socioeconomic parameters. Of the 179 parasitological stool tests, 136 (76% had one or more parasites. Prevalence of Ascaris lumbricoides was the highest 47 (34,6%, followed by Schistosoma mansoni 36 (26,5%, Giardia lamblia 31 (22,8%, E. histolytica/E. dispar 25 (18,4%, E. coli 21 (15,4%, Trichuris trichiura 19 (14%, Hymenolepis nana 16 (11,8%, Ancilostomídeos 12 (8,8%, Iodamoeba butschili 3 (2,2%, Enterobius vermicularis 1 (0,74%. The positive cases were sent to public clinic for treatments. In the school, the children received educational orientation and their family too. It was observed association between the high prevalence of intestinal parasites and habitation, environments, hygiene and sanitary conditions. It was conclude that they need to improve their life conditions. The discussions about fight for the right to the health must be continuously troubled in the school environment so that future citizens could form a new mentality about the importance of protection against diseases.

Prevalence and factors associated with intestinal parasites among food handlers of food and drinking establishments in Aksum Town, Northern Ethiopia.

Science.gov (United States)

Gezehegn, Dejen; Abay, Mebrahtu; Tetemke, Desalegn; Zelalem, Hiwet; Teklay, Hafte; Baraki, Zeray; Medhin, Girmay

2017-10-17

Various epidemiological studies indicate that the prevalence of intestinal parasites is high in developing countries and those parasites are major public health importance in Sub-Saharan Africa. Their distribution is mainly associated with poor personal hygiene, environmental sanitation and lack of access to clean water. This study was conducted to estimate the prevalence of intestinal parasitic infection and identify factors associated with intestinal parasitic infection among food handlers in the Aksum Town of Tigray Regional State, North Ethiopia. A cross-sectional study design was used among 400 randomly selected food handlers who were selected as respondents. Data were collected by face to face interviewer administered questionnaire supplemented with observational checklist. Fresh stool samples were collected from respondents and were examined microscopically for the presence of any of intestinal parasites using standard laboratory methods. Multivariable logistic regression model using Adjusted Odds Ratio (AOR) and 95% Confidence Interval (CI) was fitted to analyze the independent predictors of intestinal parasitic infections. The mean age of the food handlers included in this study was 26.0 years. Of the total respondents, 72.5% were females, 63% have completed at least secondary school educational level. Five species of Intestinal Parasites (IPs) were identified. The overall prevalence of being infected with at least one intestinal parasite was 14.5%, 95% CI (11.3, 18.0). The odds of being positive for at least one intestinal parasitic infection was 12.3 times higher among food handlers who practice medical checkup every 9 months compared to those who have a medical checkup every 3 months. The odds of being positive for intestinal parasitic infection was 3 times higher among food handlers with no formal education compared to those who have a level of education secondary school and above. Food handlers who received food hygiene and safety training were 66

Prevalence and factors associated with intestinal parasites among food handlers of food and drinking establishments in Aksum Town, Northern Ethiopia

Directory of Open Access Journals (Sweden)

Dejen Gezehegn

2017-10-01

Full Text Available Abstract Background Various epidemiological studies indicate that the prevalence of intestinal parasites is high in developing countries and those parasites are major public health importance in Sub-Saharan Africa. Their distribution is mainly associated with poor personal hygiene, environmental sanitation and lack of access to clean water. This study was conducted to estimate the prevalence of intestinal parasitic infection and identify factors associated with intestinal parasitic infection among food handlers in the Aksum Town of Tigray Regional State, North Ethiopia. Methods A cross-sectional study design was used among 400 randomly selected food handlers who were selected as respondents. Data were collected by face to face interviewer administered questionnaire supplemented with observational checklist. Fresh stool samples were collected from respondents and were examined microscopically for the presence of any of intestinal parasites using standard laboratory methods. Multivariable logistic regression model using Adjusted Odds Ratio (AOR and 95% Confidence Interval (CI was fitted to analyze the independent predictors of intestinal parasitic infections. Result The mean age of the food handlers included in this study was 26.0 years. Of the total respondents, 72.5% were females, 63% have completed at least secondary school educational level. Five species of Intestinal Parasites (IPs were identified. The overall prevalence of being infected with at least one intestinal parasite was 14.5%, 95% CI (11.3, 18.0. The odds of being positive for at least one intestinal parasitic infection was 12.3 times higher among food handlers who practice medical checkup every 9 months compared to those who have a medical checkup every 3 months. The odds of being positive for intestinal parasitic infection was 3 times higher among food handlers with no formal education compared to those who have a level of education secondary school and above. Food handlers who

Factors influencing growth and intestinal parasitic infections in preschoolers attending philanthropic daycare centers in Salvador, Northeast Region of Brazil.

Science.gov (United States)

Lander, Rebecca L; Lander, Alastair G; Houghton, Lisa; Williams, Sheila M; Costa-Ribeiro, Hugo; Barreto, Daniel L; Mattos, Angela P; Gibson, Rosalind S

2012-11-01

Poor growth and intestinal parasitic infections are widespread in disadvantaged urban children. This cross-sectional study assessed factors influencing poor growth and intestinal parasites in 376 children aged three to six years in daycare centers in Salvador, in the Northeast Region of Brazil. Data was obtained from seven daycare centers on child weight, height, socio-economic status, health and intestinal parasites in stool samples. Prevalence of moderate underweight ( -2SD), wasting and stunting was 12%, 16% and 6% respectively. Socioeconomic status, birth order, and maternal weight were predictors of poor anthropometric status. Almost 30% of children were infected with more than one intestinal parasite. Helminths (17.8%), notably Trichuris trichiura (12%) and Ascaris lumbricoides (10.5%), and protozoan Giardia duodenalis (13%) were the most common types of parasites detected. One percent of children had hookworm and Cryptosporidium sp. and 25% had non-pathogenic protozoan cysts. Boys from families with very low socio-economic status had lower linear growth and presented a greater risk of helminth infection. Deworming is considered an alternative for reducing the prevalence of intestinal parasitic infections in this age group.

Parasitic helminths: a pharmacopeia of anti-inflammatory molecules.

Science.gov (United States)

Johnston, M J G; MacDonald, J A; McKay, D M

2009-02-01

Infection with parasitic helminths takes a heavy toll on the health and well-being of humans and their domestic livestock, concomitantly resulting in major economic losses. Analyses have consistently revealed bioactive molecules in extracts of helminths or in their excretory/secretory products that modulate the immune response of the host. It is our view that parasitic helminths are an untapped source of immunomodulatory substances that, in pure form, could become new drugs (or models for drug design) to treat disease. Here, we illustrate the range of immunomodulatory molecules in selected parasitic trematodes, cestodes and nematodes, their impact on the immune cells in the host and how the host may recognize these molecules. There are many examples of the partial characterization of helminth-derived immunomodulatory molecules, but these have not yet translated into new drugs, reflecting the difficulty of isolating and fully characterizing proteins, glycoproteins and lipid-based molecules from small amounts of parasite material. However, this should not deter the investigator, since analytical techniques are now being used to accrue considerable structural information on parasite-derived molecules, even when only minute quantities of tissue are available. With the introduction of methodologies to purify and structurally-characterize molecules from small amounts of tissue and the application of high throughput immunological assays, one would predict that an assessment of parasitic helminths will yield a variety of novel drug candidates in the coming years.

Suppressor of cytokine signalling-3 inhibits Tumor necrosis factor-alpha induced apoptosis and signalling in beta cells

DEFF Research Database (Denmark)

Bruun, Christine; Heding, Peter E; Rønn, Sif G

2009-01-01

Tumor necrosis factor-alpha (TNFalpha) is a pro-inflammatory cytokine involved in the pathogenesis of several diseases including type 1 diabetes mellitus (T1DM). TNFalpha in combination with interleukin-1-beta (IL-1beta) and/or interferon-gamma (IFNgamma) induces specific destruction...

Sunlight–derived vitamin D affects interleukin-4 level, T helper 2 serum cytokines, in patients with Graves’ disease: a prospective cohort study

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Dyah Purnamasari

2015-12-01

Full Text Available Background: Graves’ disease (GD is the most common autoimmune disease leading to hyperthyroidism. The role of Th1/Th2 pathways balance in GD is still controversial. Vitamin D is reported to have an effect on those pathways. This study aims to examine the effect of sunlight exposure on vitamin D 25(OH level and Th1 and Th2 pathway-derived cytokines in GD patients. Methods: A prospective cohort study was conducted on 32 GD patients to compare the effect of sunlight exposure on vitamin D level and cytokines of Th1 and Th2 pathways between exposed and unexposed groups. Exposed group received sunlight exposure three times a week for 30 minutes each between 9–11 a.m for 1 month. Thyroid stimulating hormone (TSH, free thyroxin (fT4, vitamin D 25(OH, interferon-γ (IFN-γ and interleukin-4 (IL-4 serum levels, were investigated before and after one month of sunlight exposure. Paired t-test or Mann Whitney test were used to analyze the difference between exposed and unexposed GD groups before and after sun exposure.Results: One month of sunlight exposure increased vitamin D 25(OH level by 27.90% among exposed GD group (15.34 ng/mL to 19.62 ng/mL, p<0.001. Meanwhile, unexposed GD group’s vitamin D 25(OH level decreased from 20.48 ng/mL to 18.86 ng/mL (p<0.001. Increased vitamin D 25(OH level in exposed group was not accompanied by the increase of IL-4 level after sunlight exposure.Conclusion: Sunlight exposure increases vitamin D 25(OH serum level and may affect the level of IL-4, Th2 pathway-derived cytokine, in patients with GD. However, the role of sunlight-derived vitamin D on IFN-γ in GD patients can not be concluded in this study.

Regulation of human cytokines by Cordyceps militaris.

Science.gov (United States)

Sun, Yong; Shao, Yani; Zhang, Zhiguo; Wang, Lianfen; Mariga, Alfred M; Pang, Guangchang; Geng, Chaoyu; Ho, Chi-Tang; Hu, Qiuhui; Zhao, Liyan

2014-12-01

Cordyceps (Cordyceps militaris) exhibits many biological activities including antioxidant, inhibition of inflammation, cancer prevention, hypoglycemic, and antiaging properties, etc. However, a majority of studies involving C. militaris have focused only on in vitro and animal models, and there is a lack of direct translation and application of study results to clinical practice (e.g., health benefits). In this study, we investigated the regulatory effects of C. militaris micron powder (3 doses) on the human immune system. The study results showed that administration of C. militaris at various dosages reduced the activity of cytokines such as eotaxin, fibroblast growth factor-2, GRO, and monocyte chemoattractant protein-1. In addition, there was a significant decrease in the activity of various cytokines, including GRO, sCD40L, and tumor necrosis factor-α, and a significant downregulation of interleukin-12(p70), interferon-γ inducible protein 10, and macrophage inflammatory protein-1β activities, indicating that C. militaris at all three dosages downregulated the activity of cytokines, especially inflammatory cytokines and chemokines. Different dosages of C. militaris produced different changes in cytokines. Copyright © 2014. Published by Elsevier B.V.

Systemic T Cells Immunosuppression of Glioma Stem Cell-Derived Exosomes Is Mediated by Monocytic Myeloid-Derived Suppressor Cells.

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Rossana Domenis

Full Text Available A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes. Phenotypic characterization, cell proliferation, Th1/Th2 cytokine secretion and intracellular cytokine production were analysed by distinguishing among effector T cells, regulatory T cells and monocytes. In unfractionated PBMCs, GSC-derived exosomes inhibited T cell activation (CD25 and CD69 expression, proliferation and Th1 cytokine production, and did not affect cell viability or regulatory T-cell suppression ability. Furthermore, exosomes were able to enhance proliferation of purified CD4+ T cells. In PBMCs culture, glioma-derived exosomes directly promoted IL-10 and arginase-1 production and downregulation of HLA-DR by unstimulated CD14+ monocytic cells, that displayed an immunophenotype resembling that of monocytic myeloid-derived suppressor cells (Mo-MDSCs. Importantly, the removal of CD14+ monocytic cell fraction from PBMCs restored T-cell proliferation. The same results were observed with exosomes purified from plasma of glioblastoma patients. Our results indicate that glioma-derived exosomes suppress T-cell immune response by acting on monocyte maturation rather than on direct interaction with T cells. Selective targeting of Mo-MDSC to treat glioma should be considered with regard to how immune cells allow the acquirement of effector functions and therefore counteracting tumor progression.

Parasitic Cuscuta factor(s) and the detection by tomato initiates plant defense.

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Fürst, Ursula; Hegenauer, Volker; Kaiser, Bettina; Körner, Max; Welz, Max; Albert, Markus

2016-01-01

Dodders ( Cuscuta spp.) are holoparasitic plants that enwind stems of host plants and penetrate those by haustoria to connect to the vascular bundles. Having a broad host plant spectrum, Cuscuta spp infect nearly all dicot plants - only cultivated tomato as one exception is mounting an active defense specifically against C. reflexa . In a recent work we identified a pattern recognition receptor of tomato, "Cuscuta Receptor 1" (CuRe1), which is critical to detect a "Cuscuta factor" (CuF) and initiate defense responses such as the production of ethylene or the generation of reactive oxygen species. CuRe1 also contributes to the tomato resistance against C. reflexa . Here we point to the fact that CuRe1 is not the only relevant component for full tomato resistance but it requires additional defense mechanisms, or receptors, respectively, to totally fend off the parasite.

The Strigolactone Germination Stimulants of the Plant-Parasitic Striga and Orobanche spp. Are Derived from the Carotenoid Pathway1

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Matusova, Radoslava; Rani, Kumkum; Verstappen, Francel W.A.; Franssen, Maurice C.R.; Beale, Michael H.; Bouwmeester, Harro J.

2005-01-01

The seeds of parasitic plants of the genera Striga and Orobanche will only germinate after induction by a chemical signal exuded from the roots of their host. Up to now, several of these germination stimulants have been isolated and identified in the root exudates of a series of host plants of both Orobanche and Striga spp. In most cases, the compounds were shown to be isoprenoid and belong to one chemical class, collectively called the strigolactones, and suggested by many authors to be sesquiterpene lactones. However, this classification was never proven; hence, the biosynthetic pathways of the germination stimulants are unknown. We have used carotenoid mutants of maize (Zea mays) and inhibitors of isoprenoid pathways on maize, cowpea (Vigna unguiculata), and sorghum (Sorghum bicolor) and assessed the effects on the root exudate-induced germination of Striga hermonthica and Orobanche crenata. Here, we show that for these three host and two parasitic plant species, the strigolactone germination stimulants are derived from the carotenoid pathway. Furthermore, we hypothesize how the germination stimulants are formed. We also discuss this finding as an explanation for some phenomena that have been observed for the host-parasitic plant interaction, such as the effect of mycorrhiza on S. hermonthica infestation. PMID:16183851

Induction of Protective Immunity against Eimeria tenella, Eimeria maxima, and Eimeria acervulina Infections Using Dendritic Cell-Derived Exosomes

Science.gov (United States)

Gallego, Margarita; Lee, Sung Hyen; Lillehoj, Hyun Soon; Quilez, Joaquin; Lillehoj, Erik P.; Sánchez-Acedo, Caridad

2012-01-01

This study describes a novel immunization strategy against avian coccidiosis using exosomes derived from Eimeria parasite antigen (Ag)-loaded dendritic cells (DCs). Chicken intestinal DCs were isolated and pulsed in vitro with a mixture of sporozoite-extracted Ags from Eimeria tenella, E. maxima, and E. acervulina, and the cell-derived exosomes were isolated. Chickens were nonimmunized or immunized intramuscularly with exosomes and subsequently noninfected or coinfected with E. tenella, E. maxima, and E. acervulina oocysts. Immune parameters compared among the nonimmunized/noninfected, nonimmunized/infected, and immunized/infected groups were the numbers of cells secreting Th1 cytokines, Th2 cytokines, interleukin-16 (IL-16), and Ag-reactive antibodies in vitro and in vivo readouts of protective immunity against Eimeria infection. Cecal tonsils, Peyer's patches, and spleens of immunized and infected chickens had increased numbers of cells secreting the IL-16 and the Th1 cytokines IL-2 and gamma interferon, greater Ag-stimulated proliferative responses, and higher numbers of Ag-reactive IgG- and IgA-producing cells following in vitro stimulation with the sporozoite Ags compared with the nonimmunized/noninfected and nonimmunized/infected controls. In contrast, the numbers of cells secreting the Th2 cytokines IL-4 and IL-10 were diminished in immunized and infected chickens compared with the nonimmunized/noninfected and the nonimmunized/infected controls. Chickens immunized with Ag-loaded exosomes and infected in vivo with Eimeria oocysts had increased body weight gains, reduced feed conversion ratios, diminished fecal oocyst shedding, lessened intestinal lesion scores, and reduced mortality compared with the nonimmunized/infected controls. These results suggest that successful field vaccination against avian coccidiosis using exosomes derived from DCs incubated with Ags isolated from Eimeria species may be possible. PMID:22354026

Risk Factors and Relationship Between Intestinal Parasites and the Growth Retardation and Psychomotor Development Delays of Children in Şanlıurfa, Turkey.

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Yentur Doni, Nebiye; Yildiz Zeyrek, Fadile; Simsek, Zeynep; Gurses, Gulcan; Sahin, İbrahim

2015-12-01

The objective of this study was to determine the risk factors for and relationship among parasitic infections, growth retardation, and psychomotor developmental delays in children aged 6 years and below. This case-control study was performed in Şanlıurfa in southeastern Turkey between October and December 2007. Data were collected using a structured questionnaire, anthropometry, Ankara Development Screening Inventory, and laboratory analysis of stool specimens. The most common parasite was Giardia intestinalis (42.53%) followed by Enterobius vermicularis (27.58%), Ascaris lumbricoides (18.39%), Hymenolepis nana (5.75%), Trichuris trichiura (3.45%), Escherichia coli (1.15%), and Blastocystis spp. (1.15%). Fifty-eight percent of all children were infected with intestinal parasites; 55.2% had only one parasite, whereas 44.8% had multiple parasites. The children infected with G. intestinalis and other intestinal parasites had significantly higher levels of growth retardation and psychomotor development delay than non-infected children. Children with parasitic infections had growth delay up to 2.9 times, general development delay up to 1.9 times, language-cognitive development delay up to 2.2 times, and fine motor development delay up to 2.9 times higher than children without any parasitic infections. However, no significant relationship among intestinal parasites, gross motor development, social-self skills, and development delay was identified. The education level of parents, poor economic situation, number of households, not washing hands, playing with soil, family history of parasitic infection were the significant risk factors for intestinal parasites. Our study indicates that the presence of either malnutrition or intestinal parasites may put a child in a high-risk group for developmental delays and growth retardation. Therefore, public health interventions can embrace nationwide deworming in children.

Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations

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Peleg Rider

2016-01-01

Full Text Available Proinflammatory cytokines are potent mediators of numerous biological processes and are tightly regulated in the body. Chronic uncontrolled levels of such cytokines can initiate and derive many pathologies, including incidences of autoimmunity and cancer. Therefore, therapies that regulate the activity of inflammatory cytokines, either by supplementation of anti-inflammatory recombinant cytokines or by neutralizing them by using blocking antibodies, have been extensively used over the past decades. Over the past few years, new innovative biological agents for blocking and regulating cytokine activities have emerged. Here, we review some of the most recent approaches of cytokine targeting, focusing on anti-TNF antibodies or recombinant TNF decoy receptor, recombinant IL-1 receptor antagonist (IL-1Ra and anti-IL-1 antibodies, anti-IL-6 receptor antibodies, and TH17 targeting antibodies. We discuss their effects as biologic drugs, as evaluated in numerous clinical trials, and highlight their therapeutic potential as well as emphasize their inherent limitations and clinical risks. We suggest that while systemic blocking of proinflammatory cytokines using biological agents can ameliorate disease pathogenesis and progression, it may also abrogate the hosts defense against infections. Moreover, we outline the rational need to develop new therapies, which block inflammatory cytokines only at sites of inflammation, while enabling their function systemically.

Trypanosoma cruzi infection is a potent risk factor for non-alcoholic steatohepatitis enhancing local and systemic inflammation associated with strong oxidative stress and metabolic disorders.

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Luisina I Onofrio

2015-02-01

Full Text Available The immune mechanisms underlying experimental non-alcoholic steatohepatitis (NASH, and more interestingly, the effect of T. cruzi chronic infection on the pathogenesis of this metabolic disorder are not completely understood.We evaluated immunological parameters in male C57BL/6 wild type and TLR4 deficient mice fed with a standard, low fat diet, LFD (3% fat as control group, or a medium fat diet, MFD (14% fat in order to induce NASH, or mice infected intraperitoneally with 100 blood-derived trypomastigotes of Tulahuen strain and also fed with LFD (I+LFD or MFD (I+MFD for 24 weeks. We demonstrated that MFD by itself was able to induce NASH in WT mice and that parasitic infection induced marked metabolic changes with reduction of body weight and steatosis revealed by histological studies. The I+MFD group also improved insulin resistance, demonstrated by homeostasis model assessment of insulin resistance (HOMA-IR analysis; although parasitic infection increased the triglycerides and cholesterol plasma levels. In addition, hepatic M1 inflammatory macrophages and cytotoxic T cells showed intracellular inflammatory cytokines which were associated with high levels of IL6, IFNγ and IL17 plasmatic cytokines and CCL2 chemokine. These findings correlated with an increase in hepatic parasite load in I+MFD group demonstrated by qPCR assays. The recruitment of hepatic B lymphocytes, NK and dendritic cells was enhanced by MFD, and it was intensified by parasitic infection. These results were TLR4 signaling dependent. Flow cytometry and confocal microscopy analysis demonstrated that the reactive oxygen species and peroxinitrites produced by liver inflammatory leukocytes of MFD group were also exacerbated by parasitic infection in our NASH model.We highlight that a medium fat diet by itself is able to induce steatohepatitis. Our results also suggest a synergic effect between damage associated with molecular patterns generated during NASH and parasitic infection

Cytokines (interleukin-9, IL-17, IL-22, IL-25 and IL-33 and asthma

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Rahim Farahani

2014-01-01

Full Text Available Asthma is a reversible airway obstruction that is characterized by constriction of airway smooth muscle, hyper secretion of mucus, edema and airway hyper responsiveness (AHR, mucus secretion and thickening of the basement membrane underlying the airway epithelium. During the process of airway inflammation, complex interactions of innate and adaptive immune cells as well as structural cells and their cytokines have many important roles. It was believed that airway inflammation is orchestrated by allergen specific T helper (Th 2 cells, which recruit and accumulate in the lungs and produce a range of different effector cytokines. However, more recent studies have revealed the potential collaboration of other helper T cells and their cytokines in this process. Th17 cell may have a role in severe asthma and chronic obstructive pulmonary disease (COPD. Interleukin (IL-9-producing subset called Th9 cell, Th22 cells which primarily secrete IL-22, IL-13 and tumor necrosis factor-α and Th25 cells via producing IL-25 are believed to be important for initiating allergic reactions and developing airway inflammation. Cytokines are important in asthma and play a critical role in orchestrating the allergic inflammatory response, although the precise role of each cytokine remains to be determined. The aim of this review is to summarize the current knowledge about the possible roles of newly identified helper T cells derived cytokines (IL-9, 17, 22, 25 and IL-33 in asthma. The potential therapeutic applications emerging from the roles of these cytokines will be discussed as well.

Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus

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Rodgers, D T; Pineda, M A; Suckling, C J; Harnett, W

2015-01-01

Introduction ES-62, a phosphorylcholine (PC)-containing immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, protects against nephritis in the MRL/Lpr mouse model of systemic lupus erythematosus (SLE). However, ES-62 is not suitable for development as a therapy and thus we have designed drug-like small molecule analogues (SMAs) based around its active PC-moiety. To provide proof of concept that ES-62-based SMAs exhibit therapeutic potential in SLE, we have investigated the capacity of two SMAs to protect against nephritis when administered to MRL/Lpr mice after onset of kidney damage. Methods SMAs 11a and 12b were evaluated for their ability to suppress antinuclear antibody (ANA) generation and consequent kidney pathology in MRL/Lpr mice when administered after the onset of proteinuria. Results SMAs 11a and 12b suppressed development of ANA and proteinuria. Protection reflected downregulation of MyD88 expression by kidney cells and this was associated with reduced production of IL-6, a cytokine that exhibits promise as a therapeutic target for this condition. Conclusions SMAs 11a and 12b provide proof of principle that synthetic compounds based on the safe immunomodulatory mechanisms of parasitic worms can exhibit therapeutic potential as a novel class of drugs for SLE, a disease for which current therapies remain inadequate. PMID:26085597

Assessment of Energy Metabolic Changes in Adipose Tissue-Derived Stem Cells

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Hajmousa, Ghazaleh; Harmsen, Martin C; Di Nardo, Paolo; Dhingra, Sanjiv; Singla, Dinender K.

2017-01-01

Adipose tissue-derived stem cells (ADSC) are promising candidates for therapeutic applications in cardiovascular regenerative medicine. By definition, the phenotype ADSCs, e.g., the ubiquitous secretion of growth factors, cytokines, and extracellular matrix components is not met in vivo, which

Plasma cytokines eotaxin, MIP-1α, MCP-4, and vascular endothelial growth factor in acute lower respiratory tract infection

DEFF Research Database (Denmark)

Relster, Mette Marie; Holm, Anette; Pedersen, Court

2017-01-01

), monocyte chemoattractant protein 4 (MCP-4), and vascular endothelial growth factor (VEGF) in 40 patients hospitalized with acute lower respiratory tract infections (LRTI). The cytokines contribute to the pathogenesis of several inflammatory respiratory diseases, indicating a potential as markers for LRTI....... Patients were stratified according to etiology and severity of LRTI, based on baseline C-reactive protein and CURB-65 scores. Using a multiplex immunoassay of plasma, levels of eotaxin and MCP-4 were shown to increase from baseline until day 6 after admission to hospital. The four cytokines were unable...

Blood Cytokine Profiles Associated with Distinct Patterns of Bronchopulmonary Dysplasia among Extremely Low Birth Weight Infants.

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D'Angio, Carl T; Ambalavanan, Namasivayam; Carlo, Waldemar A; McDonald, Scott A; Skogstrand, Kristin; Hougaard, David M; Shankaran, Seetha; Goldberg, Ronald N; Ehrenkranz, Richard A; Tyson, Jon E; Stoll, Barbara J; Das, Abhik; Higgins, Rosemary D

2016-07-01

To explore differences in blood cytokine profiles among distinct bronchopulmonary dysplasia (BPD) patterns. We evaluated blood spots collected from 943 infants born at ≤1000 g and surviving to 28 days on postnatal days 1, 3, 7, 14, and 21 for 25 cytokines. Infants were assigned to the following lung disease patterns: (1) no lung disease (NLD); (2) respiratory distress syndrome without BPD; (3) classic BPD (persistent exposure to supplemental oxygen until 28 days of age); or (4) atypical BPD (period without supplemental oxygen before 28 days). Median cytokine levels for infants with BPD were compared with the IQR of results among infants with NLD. The distribution of enrolled infants by group was as follows: 69 (NLD), 73 (respiratory distress syndrome), 381 (classic BPD), and 160 (atypical BPD). The remaining 260 infants could not be classified because of missing data (104) or not fitting a predefined pattern (156). Median levels of 3 cytokines (elevated interleukin [IL]-8, matrix metalloproteinase-9; decreased granulocyte macrophage colony-stimulating factor) fell outside the IQR for at least 2 time points in both infants with atypical and classic BPD. Profiles of 7 cytokines (IL-6, IL-10, IL-18, macrophage inflammatory protein-1α, C-reactive protein, brain-derived neurotrophic factor, regulated on activation, normal T cell expressed and secreted) differed between infants with classic and atypical BPD. Blood cytokine profiles may differ between infants developing classic and atypical BPD. These dissimilarities suggest the possibility that differing mechanisms could explain the varied patterns of pathophysiology of lung disease in extremely premature infants. Copyright © 2016 Elsevier Inc. All rights reserved.

Polysaccharides from the fungus Scleroderma nitidum with anti-inflammatory potential modulate cytokine levels and the expression of Nuclear Factor kB

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Marília S. Nascimento

2012-02-01

Full Text Available Several pharmacological properties are attributed to polysaccharides and glucans derived from fungi such as tumor, anti-inflammatory, and immunomodulatory activity. In this work, the anti-inflammatory potential of polysaccharides from the fungus Scleroderma nitidum and their possible action mechanism were studied. The effect of these polymers on the inflammatory process was tested using the carrageenan and histamine-induced paw edema model and the sodium thioglycolate and zymosan-induced model. The polysaccharides from S. nitidum were effective in reducing edema (73% at 50 mg/kg and cell infiltrate (37% at 10 mg/kg in both inflammation models tested. Nitric oxide, a mediator in the inflammatory process, showed a reduction of around 26% at 10 mg/kg of body weight. Analysis of pro-and anti-inflammatory cytokines showed that in the groups treated with polysaccharides from S. nitidum there was an increase in cytokines such as IL-1ra, IL-10, and MIP-1β concomitant with the decrease in INF-γ (75% and IL-2 (22%. We observed the influence of polysaccharides on the modulation of the expression of nuclear factor κB. This compound reduced the expression of NF-κB by up to 64%. The results obtained suggest that NF-κB modulation an mechanisms that explain the anti-inflammatory effect of polysaccharides from the fungus S. nitidum.

Prediction of Radiation Esophagitis in Non–Small Cell Lung Cancer Using Clinical Factors, Dosimetric Parameters, and Pretreatment Cytokine Levels

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Peter G. Hawkins

2018-02-01

Full Text Available Radiation esophagitis (RE is a common adverse event associated with radiotherapy for non–small cell lung cancer (NSCLC. While plasma cytokine levels have been correlated with other forms of radiation-induced toxicity, their association with RE has been less well studied. We analyzed data from 126 patients treated on 4 prospective clinical trials. Logistic regression models based on combinations of dosimetric factors [maximum dose to 2 cubic cm (D2cc and generalized equivalent uniform dose (gEUD], clinical variables, and pretreatment plasma levels of 30 cytokines were developed. Cross-validated estimates of area under the receiver operating characteristic curve (AUC and log likelihood were used to assess prediction accuracy. Dose-only models predicted grade 3 RE with AUC values of 0.750 (D2cc and 0.727 (gEUD. Combining clinical factors with D2cc increased the AUC to 0.779. Incorporating pretreatment cytokine measurements, modeled as direct associations with RE and as potential interactions with the dose-esophagitis association, produced AUC values of 0.758 and 0.773, respectively. D2cc and gEUD correlated with grade 3 RE with odds ratios (ORs of 1.094/Gy and 1.096/Gy, respectively. Female gender was associated with a higher risk of RE, with ORs of 1.09 and 1.112 in the D2cc and gEUD models, respectively. Older age was associated with decreased risk of RE, with ORs of 0.992/year and 0.991/year in the D2cc and gEUD models, respectively. Combining clinical with dosimetric factors but not pretreatment cytokine levels yielded improved prediction of grade 3 RE compared to prediction by dose alone. Such multifactorial modeling may prove useful in directing radiation treatment planning.

Cytokine loops driving senescence

Czech Academy of Sciences Publication Activity Database

Bartek, Jiří; Hodný, Zdeněk; Lukáš, Jan

2008-01-01

Roč. 10, č. 8 (2008), s. 887-889 ISSN 1465-7392 Institutional research plan: CEZ:AV0Z50520514 Keywords : cellular senescence * cytokines * autocrine feedback loop Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 17.774, year: 2008

Treatment of mice with fenbendazole attenuates allergic airways inflammation and Th2 cytokine production in a model of asthma.

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Cai, Yeping; Zhou, Jiansheng; Webb, Dianne C

2009-01-01

Mouse models have provided a significant insight into the role of T-helper (Th) 2 cytokines such as IL-5 and IL-13 in regulating eosinophilia and other key features of asthma. However, the validity of these models can be compromised by inadvertent infection of experimental mouse colonies with pathogens such as oxyurid parasites (pinworms). While the benzimidazole derivative, fenbendazole (FBZ), is commonly used to treat such outbreaks, the effects of FBZ on mouse models of Th2 disease are largely unknown. In this investigation, we show that mice fed FBZ-supplemented food during the in utero and post-weaning period developed attenuated lung eosinophilia, antigen-specific IgG1 and Th2 cytokine responses in a model of asthma. Treatment of the mediastinal lymph node cells from allergic mice with FBZ in vitro attenuated cell proliferation, IL-5 and IL-13 production and expression of the early lymphocyte activation marker, CD69 on CD4(+) T cells and CD19(+) B cells. In addition, eosinophilia and Th2 responses remained attenuated after a 4-week withholding period in allergic mice treated preweaning with FBZ. Thus, FBZ modulates the amplitude of Th2 responses both in vivo and in vitro.

Mechanisms of CNS invasion and damage by parasites.

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Kristensson, Krister; Masocha, Willias; Bentivoglio, Marina

2013-01-01

Invasion of the central nervous system (CNS) is a most devastating complication of a parasitic infection. Several physical and immunological barriers provide obstacles to such an invasion. In this broad overview focus is given to the physical barriers to neuroinvasion of parasites provided at the portal of entry of the parasites, i.e., the skin and epithelial cells of the gastrointestinal tract, and between the blood and the brain parenchyma, i.e., the blood-brain barrier (BBB). A description is given on how human pathogenic parasites can reach the CNS via the bloodstream either as free-living or extracellular parasites, by embolization of eggs, or within red or white blood cells when adapted to intracellular life. Molecular mechanisms are discussed by which parasites can interact with or pass across the BBB. The possible targeting of the circumventricular organs by parasites, as well as the parasites' direct entry to the brain from the nasal cavity through the olfactory nerve pathway, is also highlighted. Finally, examples are given which illustrate different mechanisms by which parasites can cause dysfunction or damage in the CNS related to toxic effects of parasite-derived molecules or to immune responses to the infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Th17 plasticity and transition toward a pathogenic cytokine signature are regulated by cyclosporine after allogeneic SCT.

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Gartlan, Kate H; Varelias, Antiopi; Koyama, Motoko; Robb, Renee J; Markey, Kate A; Chang, Karshing; Wilkinson, Andrew N; Smith, David; Ullah, Md Ashik; Kuns, Rachel D; Raffelt, Neil C; Olver, Stuart D; Lineburg, Katie E; Teal, Bianca E; Cheong, Melody; Teng, Michele W L; Smyth, Mark J; Tey, Siok-Keen; MacDonald, Kelli P A; Hill, Geoffrey R

2017-02-14

T-helper 17 (Th17) cells have been widely implicated as drivers of autoimmune disease. In particular, Th17 cytokine plasticity and acquisition of an interleukin-17A + (IL-17A + )interferon γ(IFNγ) + cytokine profile is associated with increased pathogenic capacity. Donor Th17 polarization is known to exacerbate graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT); however, donor Th17 cytokine coexpression and plasticity have not been fully characterized. Using IL-17 "fate-mapping" mice, we identified IL-6-dependent Th17 cells early after allo-SCT, characterized by elevated expression of proinflammatory cytokines, IL-17A, IL-22, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor. This population did not maintain lineage fidelity, with a marked loss of IL-17A and IL-22 expression late posttransplant. Th17 cells were further segregated based on IFNγ coexpression, and IL-17A + IFNγ + Th17 displayed an enhanced proinflammatory phenotype. Th17 cytokine plasticity and IFNγ production were critically dependent upon donor-derived IL-12p40, and cyclosporine (CsA) treatment regulated this differentiation pathway. This observation was highly concordant with clinical samples from allo-SCT recipients receiving CsA-based immune suppression where although the IFNγ-negative-Th17 subset predominated, IFNγ + -Th17 cells were also present. In sum, Th17 polarization and ensuing differentiation are mediated by sequential inflammatory signals, which are modulated by immunosuppressive therapy, leading to distinct phenotypes within this lineage.

Salivary cytokine levels in early gingival inflammation

DEFF Research Database (Denmark)

Belstrøm, Daniel; Damgaard, Christian; Könönen, Eija

2017-01-01

Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte chemoattr......Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte...

Comparison between Two Decades of Prevalence of Intestinal Parasitic Diseases and Risk Factors in a Brazilian Urban Centre

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Maria Aparecida Alves de Oliveira Serra

2015-01-01

Full Text Available Objectives. This study’s objective was to compare the prevalence of intestinal parasites and associated risk factors in children in urban communities, in the Brazilian Northeast, between two decades. Methods. This quantitative transversal study consisted of a comparative analysis of two different samples: the first viewing the years 1992–1996 and the other through a coproepidemiological data survey undertaken in 2010-2011. Results. It was evidenced that there was a reduction of intestinal parasites and that there were improvements in the socioenvironmental conditions between the two decades evaluated. It was observed that, in the period 1992–1996, playing out in the streets was associated with a higher risk for acquiring intestinal parasites. Over the 2010-2011 period, the characteristics of more than five residents per household, houses with dirt floors, children who live in homes without piped water, and children who play out in the streets were associated with a higher risk of intestinal parasitic infection. Conclusion. The study showed a reduction of intestinal parasitic diseases to 23.8% in 2010-2011 from 81.3% in 1992–1996 and improvement of the social-sanitary conditions of the population between the decades analyzed.

Cytokines and cytokine networks target neurons to modulate long-term potentiation.

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Prieto, G Aleph; Cotman, Carl W

2017-04-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pervasiveness of parasites in pollinators.

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Sophie E F Evison

Full Text Available Many pollinator populations are declining, with large economic and ecological implications. Parasites are known to be an important factor in the some of the population declines of honey bees and bumblebees, but little is known about the parasites afflicting most other pollinators, or the extent of interspecific transmission or vectoring of parasites. Here we carry out a preliminary screening of pollinators (honey bees, five species of bumblebee, three species of wasp, four species of hoverfly and three genera of other bees in the UK for parasites. We used molecular methods to screen for six honey bee viruses, Ascosphaera fungi, Microsporidia, and Wolbachia intracellular bacteria. We aimed simply to detect the presence of the parasites, encompassing vectoring as well as actual infections. Many pollinators of all types were positive for Ascosphaera fungi, while Microsporidia were rarer, being most frequently found in bumblebees. We also detected that most pollinators were positive for Wolbachia, most probably indicating infection with this intracellular symbiont, and raising the possibility that it may be an important factor in influencing host sex ratios or fitness in a diversity of pollinators. Importantly, we found that about a third of bumblebees (Bombus pascuorum and Bombus terrestris and a third of wasps (Vespula vulgaris, as well as all honey bees, were positive for deformed wing virus, but that this virus was not present in other pollinators. Deformed wing virus therefore does not appear to be a general parasite of pollinators, but does interact significantly with at least three species of bumblebee and wasp. Further work is needed to establish the identity of some of the parasites, their spatiotemporal variation, and whether they are infecting the various pollinator species or being vectored. However, these results provide a first insight into the diversity, and potential exchange, of parasites in pollinator communities.

Recombinant Cytokines from Plants

Czech Academy of Sciences Publication Activity Database

Sirko, A.; Vaněk, Tomáš; Gora-Sochacka, A.; Redkiewicz, P.

2011-01-01

Roč. 12, č. 6 (2011), s. 3536-3552 ISSN 1661-6596 Institutional research plan: CEZ:AV0Z50380511 Keywords : cytokines * pharmaceutical proteins * plant-based production systems Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.598, year: 2011

Leishmania eukaryotic initiation factor (LeIF inhibits parasite growth in murine macrophages.

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Olga Koutsoni

Full Text Available The leishmaniases constitute neglected global public health problems that require adequate control measures, prophylactic clinical vaccines and effective and non-toxic drug treatments. In this study, we explored the potential of Leishmania infantum eukaryotic initiation factor (LieIF, an exosomal protein, as a novel anti-infective therapeutic molecule. More specifically, we assessed the efficacy of recombinant LieIF, in combination with recombinant IFN-γ, in eliminating intracellular L. donovani parasites in an in vitro macrophage model. J774A.1 macrophages were initially treated with LieIF/IFN-γ prior to in vitro infection with L. donovani stationary phase promastigotes (pre-infection treatment, and resistance to infection was observed 72 h after infection. J774A.1 macrophages were also treated with LieIF/IFN-γ after L. donovani infection (post-infection treatment, and resistance to infection was also observed at both time points tested (19 h and 72 h after infection. To elucidate the LieIF/IFN-γ-induced mechanism(s that mediate the reduction of intracellular parasite growth, we examined the generation of potent microbicidal molecules, such as nitric oxide (NO and reactive oxygen species (ROS, within infected macrophages. Furthermore, macrophages pre-treated with LieIF/IFN-γ showed a clear up-regulation in macrophage inflammatory protein 1α (MIP-1α as well as tumor necrosis factor alpha (TNF-α expression. However, significant different protein levels were not detected. In addition, macrophages pre-treated with LieIF/IFN-γ combined with anti-TNF-α monoclonal antibody produced significantly lower amounts of ROS. These data suggest that during the pre-treatment state, LieIF induces intramacrophage parasite growth inhibition through the production of TNF-α, which induces microbicidal activity by stimulating NO and ROS production. The mechanisms of NO and ROS production when macrophages are treated with LieIF after infection are probably

Prevalence and associated risk factors of intestinal parasites among children of farm workers in the southeastern Anatolian region of Turkey

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Nebiye Yentur Doni

2015-09-01

Full Text Available [b][/b]Objective. To determine the species, prevalence, and associated risk factors of intestinal parasites in farm workers’ children in a representative sample in the southeastern Anatolian region of Turkey. Materials and method. A total of 333 farm workers’ children, under the age of six years, were selected using the probability sampling method. Mean age of the children was 3.63±0.5; 55.5% were female. Data were collected using a structured questionnaire and laboratory analysis of faecal samples. Results. The overall prevalence was 44.6% and the infected children had single, double, and triple parasitic infections at 72.3%, 23.0%, and 4.7%, respectively. The most common parasite was [i]G. intestinalis[/i] (47.97%, followed by [i]E. vermicularis[/i] (37.84%, [i]T. saginata[/i] (27.03%, [i]H. nana[/i] (12.16%, and [i]A. lumbricoides[/i] (7.43%, respectively. Age, gender, illiteracy of the households, poverty, absence of toilets, bathrooms, and kitchens at the place of residence, lack of safe potable water, geophagia (soil eating habit, and being a child of a seasonal farmworker were the most significant factors associated with intestinal parasitic infection (P<0.05. [i]G. intestinalis[/i] and [i]E. vermicularis[/i] were found as the most common parasites that cause salivation, abdominal pain, and tiredness (P<0.05. Conclusion. The study revealed that health education programmes for farm workers and farmers should be improved to increase awareness about living and working conditions, in order to control intestinal parasites. However, early diagnosis and treatment services for intestinal parasites should be provided by primary health care staff in the national child screening programme in agricultural populations.

Seasonal and demographic factors influencing gastrointestinal parasitism in ungulates of Etosha National Park.

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Turner, Wendy C; Getz, Wayne M

2010-10-01

Host-parasite dynamics can be strongly affected by seasonality and age-related host immune responses. We investigated how observed variation in the prevalence and intensity of parasite egg or oocyst shedding in four co-occurring ungulate species may reflect underlying seasonal variation in transmission and host immunity. This study was conducted July 2005-October 2006 in Etosha National Park, Namibia, using indices of parasitism recorded from 1,022 fecal samples collected from plains zebra (Equus quagga), springbok (Antidorcas marsupialis), blue wildebeest (Connochaetes taurinus), and gemsbok (Oryx gazella). The presence and intensity of strongyle nematodes, Strongyloides spp. and Eimeria spp. parasites, were strongly seasonal for most host-parasite combinations, with more hosts infected in the wet season than the dry season. Strongyle intensity in zebra was significantly lower in juveniles than adults, and in springbok hosts, Eimeria spp. intensity was significantly greater in juveniles than adults. These results provide evidence that acquired immunity is less protective against strongyle nematodes than Eimeria spp. infections. The seasonal patterns in parasitism further indicate that the long dry season may limit development and survival of parasite stages in the environment and, as a result, host contact and parasite transmission.

The role of cytokines in a Porphyromonas gingivalis-induced murine abscess model.

Science.gov (United States)

Alayan, J; Gemmell, E; Ford, P; Hamlet, S; Bird, P S; Ivanovski, S; Farah, C S

2007-10-01

Porphyromonas gingivalis is an important periodontopathic bacterium that is strongly associated with periodontal disease and is part of human dental plaque. Periodontal disease results from the interaction of the host with bacterial products, and T-cell-derived cytokines remain critical in the immunoregulation of periodontal disease. The aim of this study was to examine the role of T helper type 1 [interleukin-12p40 (IL-12p40), interferon-gamma, tumour necrosis factor (TNF)] and type 2 (IL-4, IL-10) cytokines in the immune response to a subcutaneous challenge with P. gingivalis using a well-established murine abscess model, in genetically modified cytokine-specific knockout mice. IL-12p40(-/-) mice exhibited more advanced tissue destruction and a reduced inflammatory cell infiltrate after subcutaneous P. gingivalis challenge. Deficiency of IL-4 or IL-10 did not result in increased susceptibility to P. gingivalis-mediated tissue destruction. Furthermore, TNF deficiency appeared to reduce local tissue destruction. Interestingly, serum-specific antibodies suggested a strong T helper type 2 response. The results of our study indicate an important role for IL-12 in a primary P. gingivalis subcutaneous challenge.

Cytokine, chemokine, and growth factor profile of platelet-rich plasma.

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Mussano, F; Genova, T; Munaron, L; Petrillo, S; Erovigni, F; Carossa, S

2016-07-01

During wound healing, biologically active molecules are released from platelets. The rationale of using platelet-rich plasma (PRP) relies on the concentration of bioactive molecules and subsequent delivery to healing sites. These bioactive molecules have been seldom simultaneously quantified within the same PRP preparation. In the present study, the flexible Bio-Plex system was employed to assess the concentration of a large range of cytokines, chemokines, and growth factors in 16 healthy volunteers so as to determine whether significant baseline differences may be found. Besides IL-1b, IL-1ra, IL-4, IL-6, IL-8, IL-12, IL-13, IL-17, INF-γ, TNF-α, MCP-1, MIP-1a, RANTES, bFGF, PDGF, and VEGF that were already quantified elsewhere, the authors reported also on the presence of IL-2, IL-5, IL-7, IL-9, IL-10, IL-15 G-CSF, GM-CSF, Eotaxin, CXCL10 chemokine (IP-10), and MIP 1b. Among the most interesting results, it is convenient to mention the high concentrations of the HIV-suppressive and inflammatory cytokine RANTES and a statistically significant difference between males and females in the content of PDGF-BB. These data are consistent with previous reports pointing out that gender, diet, and test system affect the results of platelet function in healthy subjects, but seem contradictory when compared to other quantification assays in serum and plasma. The inconsistencies affecting the experimental results found in literature, along with the variability found in the content of bioactive molecules, urge further research, hopefully in form of randomized controlled clinical trials, in order to find definitive evidence of the efficacy of PRP treatment in various pathologic and regenerative conditions.

Decreased plasma levels of factor II + VII + X correlate with increased levels of soluble cytokine receptors in patients with malaria and meningococcal infections

DEFF Research Database (Denmark)

Bygbjerg, I C; Hansen, M B; Rønn, A M

1997-01-01

The levels of coagulation factors II + VII + X and of blood platelets (thrombocytes) as well as of cytokines and soluble cytokine receptors were studied in the patients with malaria or meningococcal infections. The coagulation factors were decreased particularly in the meningococcal patients, while...... thrombocytes were lowest in the Plasmodium falciparum malaria patients. There was no correlation between factors II + VII + X and thrombocytes, but plasma levels of coagulation factors II + VII + X were found to correlate inversely with levels of soluble interleukin-2 receptor (sIL-2R) and soluble tumour...... necrosis factor-I (sTNF-RI) in patients with malaria and meningococcal infections. Elevated sIL-2R and sTNF-RI levels and decreased coagulation factors reverted to normal within 3-5 days after initiation of therapy in P. falciparum patients followed consecutively. Estimation of coagulation factors may...

Fish Suppressors of Cytokine Signaling (SOCS): Gene Discovery, Modulation of Expression and Function

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Wang, Tiehui; Gorgoglione, Bartolomeo; Maehr, Tanja; Holland, Jason W.; Vecino, Jose L. González; Wadsworth, Simon; Secombes, Christopher J.

2011-01-01

The intracellular suppressors of cytokine signaling (SOCS) family members, including CISH and SOCS1 to 7 in mammals, are important regulators of cytokine signaling pathways. So far, the orthologues of all the eight mammalian SOCS members have been identified in fish, with several of them having multiple copies. Whilst fish CISH, SOCS3, and SOCS5 paralogues are possibly the result of the fish-specific whole genome duplication event, gene duplication or lineage-specific genome duplication may also contribute to some paralogues, as with the three trout SOCS2s and three zebrafish SOCS5s. Fish SOCS genes are broadly expressed and also show species-specific expression patterns. They can be upregulated by cytokines, such as IFN-γ, TNF-α, IL-1β, IL-6, and IL-21, by immune stimulants such as LPS, poly I:C, and PMA, as well as by viral, bacterial, and parasitic infections in member- and species-dependent manners. Initial functional studies demonstrate conserved mechanisms of fish SOCS action via JAK/STAT pathways. PMID:22203897

Production of cytokine and chemokines by human mononuclear cells and whole blood cells after infection with Trypanosoma cruzi

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Karine Rezende-Oliveira

2012-02-01

Full Text Available INTRODUCTION: The innate immune response is the first mechanism of protection against Trypanosoma cruzi, and the interaction of inflammatory cells with parasite molecules may activate this response and modulate the adaptive immune system. This study aimed to analyze the levels of cytokines and chemokines synthesized by the whole blood cells (WBC and peripheral blood mononuclear cells (PBMC of individuals seronegative for Chagas disease after interaction with live T. cruzi trypomastigotes. METHODS: IL-12, IL-10, TNF-α, TGF-β, CCL-5, CCL-2, CCL-3, and CXCL-9 were measured by ELISA. Nitrite was determined by the Griess method. RESULTS: IL-10 was produced at high levels by WBC compared with PBMC, even after incubation with live trypomastigotes. Production of TNF-α by both PBMC and WBC was significantly higher after stimulation with trypomastigotes. Only PBMC produced significantly higher levels of IL-12 after parasite stimulation. Stimulation of cultures with trypomastigotes induced an increase of CXCL-9 levels produced by WBC. Nitrite levels produced by PBMC increased after the addition of parasites to the culture. CONCLUSIONS: Surface molecules of T. cruzi may induce the production of cytokines and chemokines by cells of the innate immune system through the activation of specific receptors not evaluated in this experiment. The ability to induce IL-12 and TNF-α contributes to shift the adaptive response towards a Th1 profile.

Factors of risk associated to intestinal parasite infections among public shoolchilden in Bahia

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Camila Pereira

2014-03-01

Full Text Available This research was the aim of studying the prevalence of intestinal parasites in school children of the one public school on the periphery of the city of Jequié-BA, and the factors keys involved in the epidemiology of enteroparasites. They were analyzed fecal samples by the sedimentation technique. They obtained data on personal and socioeconomic parameters. Of the 179 parasitological stool tests, 136 (76% had one or more parasites. Prevalence of Ascaris lumbricoides was the highest 47 (34,6%, followed by Schistosoma mansoni 36 (26,5%, Giardia lamblia 31 (22,8%, E. histolytica/E. dispar 25 (18,4%, E. coli 21 (15,4%, Trichuris trichiura 19 (14%, Hymenolepis nana 16 (11,8%, Ancilostomídeos 12 (8,8%, Iodamoeba butschili 3 (2,2%, Enterobius vermicularis 1 (0,74%. The positive cases were sent to public clinic for treatments. In the school, the children received educational orientation and their family too. It was observed association between the high prevalence of intestinal parasites and habitation, environments, hygiene and sanitary conditions. It was conclude that they need to improve their life conditions. The discussions about fight for the right to the health must be continuously troubled in the school environment so that future citizens could form a new mentality about the importance of protection against diseases.

Dose-rate effects of protons on in vivo activation of nuclear factor-kappa B and cytokines in mouse bone marrow cells

International Nuclear Information System (INIS)

Rithidech, K.N.; Rusek, A.; Reungpatthanaphong, P.; Honikel, L.; Simon, S.R.

2010-01-01

The objective of this study was to determine the kinetics of nuclear factor-kappa B (NF-κB) activation and cytokine expression in bone marrow (BM) cells of exposed mice as a function of the dose rate of protons. The cytokines included in this study are pro-inflammatory (i.e., tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6) and anti-inflammatory cytokines (i.e., IL-4 and IL-10). We gave male BALB/cJ mice a whole-body exposure to 0 (sham-controls) or 1.0 Gy of 100 MeV protons, delivered at 5 or 10 mGy min -1 , the dose and dose rates found during solar particle events in space. As a reference radiation, groups of mice were exposed to 0 (sham-controls) or 1 Gy of 137 Cs γ rays (10 mGy min -1 ). After irradiation, BM cells were collected at 1.5, 3, 24 h, and 1 month for analyses (five mice per treatment group per harvest time). The results indicated that the in vivo time course of effects induced by a single dose of 1 Gy of 100 MeV protons or 137 Cs γ rays, delivered at 10 mGy min -1 , was similar. Although statistically significant levels of NF-κB activation and pro-inflammatory cytokines in BM cells of exposed mice when compared to those in the corresponding sham controls (Student's t-test, p -1 induced significant levels of anti-inflammatory cytokines. The results indicate dose-rate effects of protons.

Instruction of hematopoietic lineage choice by cytokine signaling

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Endele, Max; Etzrodt, Martin; Schroeder, Timm, E-mail: timm.schroeder@bsse.ethz.ch

2014-12-10

Hematopoiesis is the cumulative consequence of finely tuned signaling pathways activated through extrinsic factors, such as local niche signals and systemic hematopoietic cytokines. Whether extrinsic factors actively instruct the lineage choice of hematopoietic stem and progenitor cells or are only selectively allowing survival and proliferation of already intrinsically lineage-committed cells has been debated over decades. Recent results demonstrated that cytokines can instruct lineage choice. However, the precise function of individual cytokine-triggered signaling molecules in inducing cellular events like proliferation, lineage choice, and differentiation remains largely elusive. Signal transduction pathways activated by different cytokine receptors are highly overlapping, but support the production of distinct hematopoietic lineages. Cellular context, signaling dynamics, and the crosstalk of different signaling pathways determine the cellular response of a given extrinsic signal. New tools to manipulate and continuously quantify signaling events at the single cell level are therefore required to thoroughly interrogate how dynamic signaling networks yield a specific cellular response. - Highlights: • Recent studies provided definite proof for lineage-instructive action of cytokines. • Signaling pathways involved in hematopoietic lineage instruction remain elusive. • New tools are emerging to quantitatively study dynamic signaling networks over time.

Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages?

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Philippe Holzmuller

2018-04-01

Full Text Available Mononuclear phagocytes (monocytes, dendritic cells, and macrophages are among the first host cells to face intra- and extracellular protozoan parasites such as trypanosomatids, and significant expansion of macrophages has been observed in infected hosts. They play essential roles in the outcome of infections caused by trypanosomatids, as they can not only exert a powerful antimicrobial activity but also promote parasite proliferation. These varied functions, linked to their phenotypic and metabolic plasticity, are exerted via distinct activation states, in which l-arginine metabolism plays a pivotal role. Depending on the environmental factors and immune response elements, l-arginine metabolites contribute to parasite elimination, mainly through nitric oxide (NO synthesis, or to parasite proliferation, through l-ornithine and polyamine production. To survive and adapt to their hosts, parasites such as trypanosomatids developed mechanisms of interaction to modulate macrophage activation in their favor, by manipulating several cellular metabolic pathways. Recent reports emphasize that some excreted–secreted (ES molecules from parasites and sugar-binding host receptors play a major role in this dialog, particularly in the modulation of the macrophage’s inducible l-arginine metabolism. Preventing l-arginine dysregulation by drugs or by immunization against trypanosomatid ES molecules or by blocking partner host molecules may control early infection and is a promising way to tackle neglected diseases including Chagas disease, leishmaniases, and African trypanosomiases. The present review summarizes recent knowledge on trypanosomatids and their ES factors with regard to their influence on macrophage activation pathways, mainly the NO synthase/arginase balance. The review ends with prospects for the use of biological knowledge to develop new strategies of interference in the infectious processes used by trypanosomatids, in particular for the

Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats.

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Ram, Mahendra; Singh, Vishakha; Kumawat, Sanjay; Kant, Vinay; Tandan, Surendra Kumar; Kumar, Dinesh

2016-01-01

Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-α and the mRNA of IL-1β and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients. Copyright © 2015

c-MPL provides tumor-targeted T-cell receptor-transgenic T cells with costimulation and cytokine signals.

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Nishimura, Christopher D; Brenner, Daniel A; Mukherjee, Malini; Hirsch, Rachel A; Ott, Leah; Wu, Meng-Fen; Liu, Hao; Dakhova, Olga; Orange, Jordan S; Brenner, Malcolm K; Lin, Charles Y; Arber, Caroline

2017-12-21

Adoptively transferred T-cell receptor (TCR)-engineered T cells depend on host-derived costimulation and cytokine signals for their full and sustained activation. However, in patients with cancer, both signals are frequently impaired. Hence, we developed a novel strategy that combines both essential signals in 1 transgene by expressing the nonlymphoid hematopoietic growth factor receptor c-MPL (myeloproliferative leukemia), the receptor for thrombopoietin (TPO), in T cells. c-MPL signaling activates pathways shared with conventional costimulatory and cytokine receptor signaling. Thus, we hypothesized that host-derived TPO, present in the tumor microenvironment, or pharmacological c-MPL agonists approved by the US Food and Drug Administration could deliver both signals to c-MPL-engineered TCR-transgenic T cells. We found that c-MPL + polyclonal T cells expand and proliferate in response to TPO, and persist longer after adoptive transfer in immunodeficient human TPO-transgenic mice. In TCR-transgenic T cells, c-MPL activation enhances antitumor function, T-cell expansion, and cytokine production and preserves a central memory phenotype. c-MPL signaling also enables sequential tumor cell killing, enhances the formation of effective immune synapses, and improves antileukemic activity in vivo in a leukemia xenograft model. We identify the type 1 interferon pathway as a molecular mechanism by which c-MPL mediates immune stimulation in T cells. In conclusion, we present a novel immunotherapeutic strategy using c-MPL-enhanced transgenic T cells responding to either endogenously produced TPO (a microenvironment factor in hematologic malignancies) or c-MPL-targeted pharmacological agents. © 2017 by The American Society of Hematology.

PREVALENCE, RISK FACTORS AND SYMPTOMS ASSOCIATED TO INTESTINAL PARASITE INFECTIONS AMONG PATIENTS WITH GASTROINTESTINAL DISORDERS IN NAHAVAND, WESTERN IRAN

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Hamed KIANI

2016-01-01

Full Text Available We studied the prevalence of intestinal parasites (IPs, their risk factors and associated symptoms among patients with gastrointestinal disorders. A total of 1,301 participants aged 22 days-90 years were enrolled in this study. We used a structured questionnaire to obtain socio-demographic and stool examination to investigate intestinal parasite infections. Data analysis was performed using SPSS16. The overall prevalence of intestinal parasites (IPs was 32.2% (419/1,301. Three hundred and fifty nine cases/1,301 (27.6% were infected with a single parasite and 60/1,301 cases (4.6% presented polyparasitism. The most common IP was Blastocystis sp. 350/1,301 (26.9%, followed by Entamoeba coli 38/1,301 (2.92%, Giardia lamblia 30/1,301 (2.3% and Cryptosporidium spp. 17/1,301 (1.3%. Regarding the socio-demographic variables, educational status (p = 0.001, contact with domestic animals and soil (p = 0.02, age above 15 years (p = 0.001 and seasons (p = 0.001 were significantly associated to intestinal parasitic infections. Concerning clinical characteristics, the presence of IPs was significantly associated to diarrhea (OR = 1.57; CI 95% = 1.24-1.98; p < 0.001 and dysentery (OR = 1.94; CI 95% = 1.03-3.66; p < 0.04. Our findings suggest that IPs are one of the main causal agents of gastrointestinal disorders. Improving the knowledge on local risk factors such as poverty, low level of education, poor sanitation, contact with soil and contact with domestic animal is warranted.

Genetics of simple and complex host-parasite interactions

International Nuclear Information System (INIS)

Sidhu, G.S.; Webster, J.M.

1977-01-01

In nature a host plant can be viewed as a miniature replica of an ecological system where true and incidental parasites share the same habitat. Consequently, they influence each other's presence directly by interspecific interaction, and indirectly by inducing changes in the host's physiology and so form disease complexes. Since all physiological phenomena have their counterpart in the respective genetic systems of interacting organisms, valuable genetic information can be derived from the analysis of complex parasitic systems. Disease complexes may be classified according to the nature of interaction between various parasites on the same host. One parasite may nullify the host's resistance to another (e.g. Tomato - Meloidogyne incognita + Fusarium oxysporum lycopersici system). Conversely, a parasite may invoke resistance in the host against another parasite (e.g. Tomato - Fusarium oxysporum lycopersici + Verticillium albo atrum system). From the study of simple parasitic systems we know that resistance versus susceptibility against a single parasite is normally monogenically controlled. However, when more than one parasite interacts to invoke or nullify each other's responses on the same host plant, the genetic results suggest epistatic ratios. Nevertheless, epistatic ratios have been obtained also from simple parasitic systems owing to gene interaction. The epistatic ratios obtained from complex and simple parasitic systems are contrasted and compared. It is suggested that epistatic ratios obtained from simple parasitic systems may, in fact, be artifacts resulting from complex parasitic associations that often occur in nature. Polygenic inheritance and the longevity of a cultivar is also discussed briefly in relation to complex parasitic associations. Induced mutations can play a significant role in the study of complex parasitic associations, and thus can be very useful in controlling plant diseases

Cytokine expression and cytokine-based T-cell profiling in occupational medicamentosa-like dermatitis due to trichloroethylene.

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Xueqin, Yang; Wenxue, Li; Peimao, Li; Wen, Zhang; Xianqing, Huang; Zhixiong, Zhuang

2018-05-15

Early diagnosis and treatment of occupational medicamentosa-like dermatitis due to trichloroethylene (OMLDT) are absence of specific and reliable diagnostic/therapeutic biomarkers. This study was conducted on 30 cases of OMLDT, 58 workers exposed to trichloroethylene (TCE) and 40 unexposed controls in order to identify any cytokine signatures that give an index to CD4 + T cell differential and serve as biomarkers of OMLDT. Expression profiles of Th 1 , Th 2 , Th 17 and Treg cell type-specifying transcription factors and cytokines were analyzed using real time quantitative PCR (RT-qPCR) assay. To explore whether such expression profiles reflected their steady state plasma levels, a Luminex liquid fluorescence analysis was conducted. We found that the expression of transcription factors FoxP3 transcription factors (P = 0.006 and P < 0.0001) and IL-10 cytokine (P = 0.0008 and P < 0.0001) of the Treg subset were significantly higher in patients than TCE exposure workers and unexposed controls, suggesting that Treg cells were active after the occurrence of OMLDT. The transcript levels of IL-6 were significantly lower in the TCE exposure groups including patients and exposure workers as compared to the unexposed controls (P < 0.0001 and P = 0.0008). Circulating levels of assessed cytokines of IL-6 (P = 0.001 and P = 0.011) and TFN-α (P = 0.005 and P < 0.0001) were lower in the exposure groups than in the unexposed controls. Compared to the controls, the levels of IL-10 in patients were higher (P = 0.001 and P = 0.0008). There was a significantly positive correlation between the plasma levels IL-6 and IL-10 in TCE exposed workers. These alterations in the expression of transcription factors and cytokines highlight the underlying dysregulation of T cell subsets in OMLDT that reflect an immune tolerance or immune inhibition. Therefore, the elevation of IL-10 level may be a kind of pathogenesis indicator, and the decline in IL

Promotion of angiogenesis and proliferation cytokines patterns in peritoneal fluid from women with endometriosis.

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Rakhila, Halima; Al-Akoum, Mahera; Bergeron, Marie-Eve; Leboeuf, Mathieu; Lemyre, Madeleine; Akoum, Ali; Pouliot, Marc

2016-08-01

Studies have long sought specific cytokines that could characterize endometriosis. Either due to variations between study designs regarding the assessment criteria for the cytokine or to low power resulting from small sample size, no factor proved to be sufficiently specific to endometriosis. In other clinical fields, a combination of several markers proved to be more powerful than a single-molecule approach. As well, in the context of endometriosis, simultaneous assessment of several cytokines present in the peritoneal fluid might help in unveiling patho-physiological processes, thus contributing to a better understanding of the condition. Therefore, the objective of this study was to investigate peritoneal fluid cytokines-derived of endometriotic women. For this retrospective case-control study, peritoneal fluid samples were obtained at laparoscopy and assessed by multiplex. Our data showed distinct patterns of peritoneal fluid cytokine concentrations in endometriotic women most notably a marked increase in EGF, FGF-2, IL-1α, MIP-1β, TGFα, PDGF-AA, PDGF-BB, MCP-3, sCD40L, Gro Pan, IL-17α, MDC and Rantes. The overall effect of fertility status revealed a significant difference for only one cytokine, namely MDC. Furthermore, FLT-3L and IP-10 levels were decreased in endometriosis patients, the former in both menstrual cycle phases and the latter in the secretory phase. A significant inverse Pearson correlation (pendometriosis patients at stages III-IV and in the secretory phase. These changes may exacerbate the local peritoneal angiogenic and proliferative reaction observed in women with endometriosis, and contributes to its pathophysiology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33.

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Osbourn, Megan; Soares, Dinesh C; Vacca, Francesco; Cohen, E Suzanne; Scott, Ian C; Gregory, William F; Smyth, Danielle J; Toivakka, Matilda; Kemter, Andrea M; le Bihan, Thierry; Wear, Martin; Hoving, Dennis; Filbey, Kara J; Hewitson, James P; Henderson, Holly; Gonzàlez-Cìscar, Andrea; Errington, Claire; Vermeren, Sonja; Astier, Anne L; Wallace, William A; Schwarze, Jürgen; Ivens, Alasdair C; Maizels, Rick M; McSorley, Henry J

2017-10-17

Infection by helminth parasites is associated with amelioration of allergic reactivity, but mechanistic insights into this association are lacking. Products secreted by the mouse parasite Heligmosomoides polygyrus suppress type 2 (allergic) immune responses through interference in the interleukin-33 (IL-33) pathway. Here, we identified H. polygyrus Alarmin Release Inhibitor (HpARI), an IL-33-suppressive 26-kDa protein, containing three predicted complement control protein (CCP) modules. In vivo, recombinant HpARI abrogated IL-33, group 2 innate lymphoid cell (ILC2) and eosinophilic responses to Alternaria allergen administration, and diminished eosinophilic responses to Nippostrongylus brasiliensis, increasing parasite burden. HpARI bound directly to both mouse and human IL-33 (in the cytokine's activated state) and also to nuclear DNA via its N-terminal CCP module pair (CCP1/2), tethering active IL-33 within necrotic cells, preventing its release, and forestalling initiation of type 2 allergic responses. Thus, HpARI employs a novel molecular strategy to suppress type 2 immunity in both infection and allergy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Human parasitic protozoan infection to infertility: a systematic review.

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Shiadeh, Malihe Nourollahpour; Niyyati, Maryam; Fallahi, Shirzad; Rostami, Ali

2016-02-01

Protozoan parasitic diseases are endemic in many countries worldwide, especially in developing countries, where infertility is a major burden. It has been reported that such infections may cause infertility through impairment in male and female reproductive systems. We searched Medline, PubMed, and Scopus databases and Google scholar to identify the potentially relevant studies on protozoan parasitic infections and their implications in human and animal model infertility. Literature described that some of the protozoan parasites such as Trichomonas vaginalis may cause deformities of the genital tract, cervical neoplasia, and tubal and atypical pelvic inflammations in women and also non-gonoccocal urethritis, asthenozoospermia, and teratozoospermia in men. Toxopalasma gondii could cause endometritis, impaired folliculogenesis, ovarian and uterine atrophy, adrenal hypertrophy, vasculitis, and cessation of estrus cycling in female and also decrease in semen quality, concentration, and motility in male. Trypanosoma cruzi inhibits cell division in embryos and impairs normal implantation and development of placenta. Decrease in gestation rate, infection of hormone-producing glands, parasite invasion of the placenta, and overproduction of inflammatory cytokines in the oviducts and uterine horns are other possible mechanisms induced by Trypanosoma cruzi to infertility. Plasmodium spp. and Trypanosoma brucei spp. cause damage in pituitary gland, hormonal disorders, and decreased semen quality. Entamoeba histolytica infection leads to pelvic pain, salpingitis, tubo-ovarian abscess, and genital ulcers. Cutaneous and visceral leishmaniasis can induce genital lesion, testicular amyloidosis, inflammation of epididymis, prostatitis, and sperm abnormality in human and animals. In addition, some epidemiological studies have reported that rates of protozoan infections in infertile patients are higher than healthy controls. The current review indicates that protozoan parasitic

The SaeR/S gene regulatory system induces a pro-inflammatory cytokine response during Staphylococcus aureus infection.

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Robert L Watkins

Full Text Available Community-associated methicillin-resistant Staphylococcus aureus accounts for a large portion of the increased staphylococcal disease incidence and can cause illness ranging from mild skin infections to rapidly fatal sepsis syndromes. Currently, we have limited understanding of S. aureus-derived mechanisms contributing to bacterial pathogenesis and host inflammation during staphylococcal disease. Herein, we characterize an influential role for the saeR/S two-component gene regulatory system in mediating cytokine induction using mouse models of S. aureus pathogenesis. Invasive S. aureus infection induced the production of localized and systemic pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α, interferon gamma (IFN-γ, interleukin (IL-6 and IL-2. In contrast, mice infected with an isogenic saeR/S deletion mutant demonstrated significantly reduced pro-inflammatory cytokine levels. Additionally, secreted factors influenced by saeR/S elicited pro-inflammatory cytokines in human blood ex vivo. Our study further demonstrated robust saeR/S-mediated IFN-γ production during both invasive and subcutaneous skin infections. Results also indicated a critical role for saeR/S in promoting bacterial survival and enhancing host mortality during S. aureus peritonitis. Taken together, this study provides insight into specific mechanisms used by S. aureus during staphylococcal disease and characterizes a relationship between a bacterial global regulator of virulence and the production of pro-inflammatory mediators.

Parasitic manipulation and neuroinflammation: Evidence from the system Microphallus papillorobustus (Trematoda - Gammarus (Crustacea

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Thomas Frederic

2010-04-01

Full Text Available Abstract Background Neuropathological consequences of neuroinflammatory processes have been implicated in a wide range of diseases affecting the central nervous system (CNS. Glial cells, the resident immune cells of the CNS, respond to tissue injury by releasing proinflammatory cytokines and free radicals such as nitric oxide. We explored the possibility that neuroimmune responses are involved in parasitic manipulation of host behavior in a trematode-crustacean association. The cerebral larva of the flatworm Microphallus papillorobustus alters responses to environmental stimuli - and thus reflex pathways - in the crustacean Gammarus insensibilis, in a way that enhances predation of the crustacean by birds, definitive hosts of the parasite. Results Immunocytochemical experiments followed by confocal microscopy were performed to study the distribution of glutamine synthetase, a glial cell marker, and nitric oxide synthase in the brain of gammarids. Astrocyte-like glia and their processes were abundant at the surface of the parasites while levels of nitric oxide synthase were elevated at the host-parasite interface in the brain of gammarids harboring mature cerebral larvae and demonstrating altered behavior. Conclusion Taken together these results lend support to the neuroinflammation hypothesis whereby a chronic CNS specific immune response induced by the parasite plays a role in the disruption of neuromodulation, neuronal integrity, and behavior in infected hosts.

Prevalence and factors associated with intestinal parasitic infections among food handlers of Southern Ethiopia: cross sectional study.

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Mama, Mohammedaman; Alemu, Getaneh

2016-02-01

Globally about one third of the total population is estimated to be infected with intestinal parasites, of which, the majority are people living in tropical and sub-tropical parts of the world. Cases of intestinal parasitosis are also highly abundant in Ethiopia and hence the aim of present study was to assess prevalence and predictors of intestinal parasitic infections among food handlers working in Arba Minch University students' cafeteria, South Ethiopia. A cross sectional study was conducted among food handlers working in Arba Minch University from April to June, 2015. A pretested structured questionnaire was used for collecting data about socio-demographic characteristics and possible risk factors. Stool specimens were collected and examined microscopically for the presence of eggs, cysts and trophozoites of intestinal parasites. Data entry and analysis were done using SPSS version 20 software. A total of 376 food handlers were enrolled in the study of which thirty one of them were not willing to participate for a stool examination. The majority of study participants were females 273 (72.6 %). About 123 (36 %) of food handlers were found to be positive for different intestinal parasites with the most abundant parasite of Entamoeba histolytica/dispar 48 (14 %) followed by Ascaris lumbricoides 32 (9.27 %). Finger nail status (AOR: 2.2, 95 % CI: 1.29-3.72), hand washing practice after toilet (AOR: 1.71, 95 % CI: 1.06-2.77), hand washing practice before food handling (AOR: 1.69, 95 % CI: 1.04-2.75), preparing food when suffering from diseases (AOR: 3.08, 95 % CI: 1.17-8.13), and using common knife for cutting raw flesh food and other food (AOR: 1.72, 95 % CI: 1.01-2.92) were independent predictors of intestinal parasitic infection among the food handlers. This study revealed a high prevalence of intestinal parasites among food handlers. Since most of the intestinal parasites are transmitted by the feco-oral route, food handlers could be an important source of

Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A

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Liu, Yanzhen; Mei, Chenfang [State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070 (China); Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou 510070 (China); Liu, Hao [Affiliated Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou 510095 (China); Wang, Hongsheng [Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Zeng, Guoqu; Lin, Jianhui [State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070 (China); Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou 510070 (China); Xu, Meiying, E-mail: xumy@gdim.cn [State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070 (China); Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou 510070 (China)

2014-09-05

Highlights: • Effects of BPA on the cytokines expression of human macrophages were investigated. • BPA increased pro-inflammation cytokines TNF-α and IL-6 production. • BPA decreased anti-inflammation IL-10 and TGF-β production. • ERα/β/ERK/NF-κB signaling involved in BPA-mediated cytokines expression. - Abstract: Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is often associated with dysregulated immune homeostasis, but the mechanisms remain unclear. In the present study, the effects of BPA on the cytokines responses of human macrophages were investigated. Treatment with BPA increased pro-inflammation cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production, but decreased anti-inflammation cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) production in THP1 macrophages, as well as in primary human macrophages. BPA effected cytokines expression through estrogen receptor α/β (ERα/β)-dependent mechanism with the evidence of ERα/β antagonist reversed the expression of cytokines. We also identified that activation of extracellular regulated protein kinases (ERK)/nuclear factor κB (NF-κB) signal cascade marked the effects of BPA on cytokines expression. Our results indicated that BPA effected inflammatory responses of macrophages via modulating of cytokines expression, and provided a new insight into the link between exposure to BPA and human health.

Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A

International Nuclear Information System (INIS)

Liu, Yanzhen; Mei, Chenfang; Liu, Hao; Wang, Hongsheng; Zeng, Guoqu; Lin, Jianhui; Xu, Meiying

2014-01-01

Highlights: • Effects of BPA on the cytokines expression of human macrophages were investigated. • BPA increased pro-inflammation cytokines TNF-α and IL-6 production. • BPA decreased anti-inflammation IL-10 and TGF-β production. • ERα/β/ERK/NF-κB signaling involved in BPA-mediated cytokines expression. - Abstract: Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is often associated with dysregulated immune homeostasis, but the mechanisms remain unclear. In the present study, the effects of BPA on the cytokines responses of human macrophages were investigated. Treatment with BPA increased pro-inflammation cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production, but decreased anti-inflammation cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) production in THP1 macrophages, as well as in primary human macrophages. BPA effected cytokines expression through estrogen receptor α/β (ERα/β)-dependent mechanism with the evidence of ERα/β antagonist reversed the expression of cytokines. We also identified that activation of extracellular regulated protein kinases (ERK)/nuclear factor κB (NF-κB) signal cascade marked the effects of BPA on cytokines expression. Our results indicated that BPA effected inflammatory responses of macrophages via modulating of cytokines expression, and provided a new insight into the link between exposure to BPA and human health

Host-Parasite Interactions from the Inside: Plant Reproductive Ontogeny Drives Specialization in Parasitic Insects.

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Thomas Boivin

Full Text Available Host plant interactions are likely key drivers of evolutionary processes involved in the diversification of phytophagous insects. Granivory has received substantial attention for its crucial role in shaping the interaction between plants and their seed parasites, but fine-scale mechanisms explaining the role of host plant reproductive biology on specialization of seed parasites remain poorly described. In a comparative approach using plant histological techniques, we tested the hypotheses that different seed parasite species synchronize their life cycles to specific stages in seed development, and that the stage they target depends on major differences in seed development programs. In a pinaceous system, seed storage products are initiated before ovule fertilization and the wasps target the ovule's nucellus during megagametogenesis, a stage at which larvae may benefit from the by-products derived from both secreting cells and dying nucellar cells. In a cupressaceous system, oviposition activity peaks later, during embryogenesis, and the wasps target the ovule's megagametophyte where larvae may benefit from cell disintegration during embryogenesis. Our cytohistological approach shows for the first time how, despite divergent oviposition targets, different parasite species share a common strategy that consists of first competing for nutrients with developing plant structures, and then consuming these developed structures to complete their development. Our results support the prediction that seed developmental program is an axis for specialization in seed parasites, and that it could be an important parameter in models of their ecological and taxonomic divergence. This study provides the basis for further investigating the possibility of the link between plant ontogeny and pre-dispersal seed parasitism.

Cytokine induction of sol–gel-derived TiO2 and SiO2 coatings on metallic substrates after implantation to rat femur

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Urbanski W

2017-02-01

Full Text Available Wiktor Urbanski,1 Krzysztof Marycz,2 Justyna Krzak,3 Celina Pezowicz,4 Szymon Feliks Dragan1 1Department of Orthopaedic Surgery and Traumatology, Wroclaw University Hospital, 2Electron Microscope Laboratory, Wroclaw University of Environmental and Life Sciences, 3Institute of Materials Science and Applied Mechanics, 4Division of Biomedical Engineering and Experimental Mechanics, Wroclaw University of Technology, Wroclaw, Poland Abstract: Material surface is a key determinant of host response on implanted biomaterial. Therefore, modification of the implant surface may optimize implant–tissue reactions. Inflammatory reaction is inevitable after biomaterial implantation, but prolonged inflammation may lead to adverse reactions and subsequent implant failure. Proinflammatory activities of cytokines like interleukin (IL-1, IL-6, and tumor necrosis factor-alpha (TNF-α are attractive indicators of these processes and ultimately characterize biocompatibility. The objective of the study was to evaluate local cytokine production after implantation of stainless steel 316L (SS and titanium alloy (Ti6Al4V biomaterials coated with titanium dioxide (TiO2 and silica (SiO2 coatings prepared by sol–gel method. Biomaterials were implanted into rat femur and after 12 weeks, bones were harvested. Bone–implant tissue interface was evaluated; immunohistochemical staining was performed to identify IL-6, TNF-α, and Caspase-1. Histomorphometry (AxioVision Rel. 4.6.3 software of tissue samples was performed in order to quantify the cytokine levels. Both the oxide coatings on SS and Ti6Al4V significantly reduced cytokine production. However, the lowest cytokine levels were observed in TiO2 groups. Cytokine content in uncoated groups was lower in Ti6Al4V than in SS, although coating of either metal reduced cytokine production to similar levels. Sol–gel TiO2 or SiO2 coatings reduced significantly the production of proinflammatory cytokines by local tissues

Identification of loci controlling restriction of parasite growth in experimental Taenia crassiceps cysticercosis.

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Ruben Ramirez-Aquino

2011-12-01

Full Text Available Human neurocysticercosis (NC caused by Taenia solium is a parasitic disease of the central nervous system that is endemic in many developing countries. In this study, a genetic approach using the murine intraperitoneal cysticercosis caused by the related cestode Taenia crassiceps was employed to identify host factors that regulate the establishment and proliferation of the parasite. A/J mice are permissive to T. crassiceps infection while C57BL/6J mice (B6 are comparatively restrictive, with a 10-fold difference in numbers of peritoneal cysticerci recovered 30 days after infection. The genetic basis of this inter-strain difference was explored using 34 AcB/BcA recombinant congenic strains derived from A/J and B6 progenitors, that were phenotyped for T. crassiceps replication. In agreement with their genetic background, most AcB strains (A/J-derived were found to be permissive to infection while most BcA strains (B6-derived were restrictive with the exception of a few discordant strains, together suggesting a possible simple genetic control. Initial haplotype association mapping using >1200 informative SNPs pointed to linkages on chromosomes 2 (proximal and 6 as controlling parasite replication in the AcB/BcA panel. Additional linkage analysis by genome scan in informative [AcB55xDBA/2]F1 and F2 mice (derived from the discordant AcB55 strain, confirmed the effect of chromosome 2 on parasite replication, and further delineated a major locus (LOD = 4.76, p<0.01; peak marker D2Mit295, 29.7 Mb that we designate Tccr1 (T. crassiceps cysticercosis restrictive locus 1. Resistance alleles at Tccr1 are derived from AcB55 and are inherited in a dominant fashion. Scrutiny of the minimal genetic interval reveals overlap of Tccr1 with other host resistance loci mapped to this region, most notably the defective Hc/C5 allele which segregates both in the AcB/BcA set and in the AcB55xDBA/2 cross. These results strongly suggest that the complement component 5 (C5

Identification of Loci Controlling Restriction of Parasite Growth in Experimental Taenia crassiceps Cysticercosis

Science.gov (United States)

Fortin, Anny; Sciutto-Conde, Edda; Fragoso-González, Gladis; Gros, Philippe; Aguilar-Delfin, Irma

2011-01-01

Human neurocysticercosis (NC) caused by Taenia solium is a parasitic disease of the central nervous system that is endemic in many developing countries. In this study, a genetic approach using the murine intraperitoneal cysticercosis caused by the related cestode Taenia crassiceps was employed to identify host factors that regulate the establishment and proliferation of the parasite. A/J mice are permissive to T. crassiceps infection while C57BL/6J mice (B6) are comparatively restrictive, with a 10-fold difference in numbers of peritoneal cysticerci recovered 30 days after infection. The genetic basis of this inter-strain difference was explored using 34 AcB/BcA recombinant congenic strains derived from A/J and B6 progenitors, that were phenotyped for T. crassiceps replication. In agreement with their genetic background, most AcB strains (A/J-derived) were found to be permissive to infection while most BcA strains (B6-derived) were restrictive with the exception of a few discordant strains, together suggesting a possible simple genetic control. Initial haplotype association mapping using >1200 informative SNPs pointed to linkages on chromosomes 2 (proximal) and 6 as controlling parasite replication in the AcB/BcA panel. Additional linkage analysis by genome scan in informative [AcB55xDBA/2]F1 and F2 mice (derived from the discordant AcB55 strain), confirmed the effect of chromosome 2 on parasite replication, and further delineated a major locus (LOD = 4.76, p<0.01; peak marker D2Mit295, 29.7 Mb) that we designate Tccr1 (T. crassiceps cysticercosis restrictive locus 1). Resistance alleles at Tccr1 are derived from AcB55 and are inherited in a dominant fashion. Scrutiny of the minimal genetic interval reveals overlap of Tccr1 with other host resistance loci mapped to this region, most notably the defective Hc/C5 allele which segregates both in the AcB/BcA set and in the AcB55xDBA/2 cross. These results strongly suggest that the complement component 5 (C5) plays a

Inflammation-modulating cytokine profile and lipid interaction in HIV-related risk factors for cardiovascular diseases

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Gori E

2016-11-01

Full Text Available Elizabeth Gori,1,2 Takafira Mduluza,3,4 Mudavanhu Nyagura,2 Babill Stray-Pedersen,5 Zvenyika Alfred Gomo1 1Chemical Pathology Department, College of Health Sciences, 2Preclinical Veterinary Studies Department, Faculty of Veterinary Sciences, 3Biochemistry Department, University of Zimbabwe, Harare, Zimbabwe; 4School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; 5Institute of Clinical Medicine, University in Oslo, Oslo University Hospital, Oslo, Norway Abstract: HIV infection and antiretroviral therapy (ART are associated with changes in plasma levels of lipoproteins, thus posing the risk of cardiovascular complications in infected individuals. The alteration in plasma lipoprotein levels results from dysregulation of inflammation-modulating cytokines that control lipid metabolism. Little is understood regarding the relationship between the cytokines and serum lipid levels, which have been reported to be altered in adults receiving ART. The objective of this study was to describe the profiles of inflammation-modulating cytokines and their relationship to lipids as cardiovascular disease (CVD risk factors in HIV infection. This observational cross-sectional study measured plasma levels of interleukin (IL-10, tumor necrosis factor-alpha (TNF-α, IL-4, total cholesterol (TC, and high-density lipoprotein cholesterol (HDL-c in HIV-infected and uninfected adults. A total of 219 HIV-infected participants were enrolled from an HIV treatment center; of them, 187 were receiving ART and 32 were ART naïve, while 65 were HIV-uninfected blood donors. HIV-infected individuals had higher levels of IL-10 (HIV-infected ART-naïve [P=0.0024] and ART-receiving [P=0.033] than their uninfected counterparts. ART-naïve subjects had significantly higher plasma levels of IL-10 than ART-receiving subjects (P=0.0014. No significant difference was observed in plasma levels of IL-4 and TNF

Modulation of Female Genital Tract-Derived Dendritic Cell Migration and Activation in Response to Inflammatory Cytokines and Toll-Like Receptor Agonists.

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Shey, Muki S; Maharaj, Niren; Archary, Derseree; Ngcapu, Sinaye; Garrett, Nigel; Abdool Karim, Salim; Passmore, Jo-Ann S

2016-01-01

HIV transmission across the genital mucosa is a major mode of new HIV infections in women. The probability of infection may be influenced by several factors including recruitment and activation of HIV target cells, such as dendritic cells (DCs) and cytokine production, associated with genital inflammation. We evaluated the role of inflammatory cytokines and TLR signaling in migration and activation of genital tract DCs in the human cervical explant model. Hysterectomy tissues from 10 HIV-negative and 7 HIV-positive donor women were separated into ecto- and endocervical explants, and incubated with inflammatory cytokines (TNF-α, IL-1β, IL-8, MIP-1β) or agonists for TLR4 (LPS), TLR2/1 (PAM3) and TLR7/8 (R848). Migration (frequency) and activation (HLA-DR expression) of myeloid and plasmacytoid DCs and Langerhans cells were measured by flow cytometry. We observed that cytokines, LPS and PAM3 induced activation of migrating myeloid and plasmacytoid DCs. LPS induced a 3.6 fold lower levels of migration of plasmacytoid DCs from HIV-infected women compared with HIV-uninfected women (median activation indices of 2.932 vs 0.833). There was however a 4.5 fold increase in migration of Langerhans cells in HIV-infected compared with HIV-uninfected women in response to cytokines (median activation indices of 3.539 vs 0.77). Only TLR agonists induced migration and activation of DCs from endocervical explants. Hormonal contraception use was associated with an increase in activation of DC subsets in the endo and ectocervical explants. We conclude that inflammatory signals in the female genital tract induced DC migration and activation, with possible important implications for HIV susceptibility of cervical tissues.

Identification of novel loci associated with gastrointestinal parasite resistance in a Red Maasai x Dorper backcross population.

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Magda Vieira Benavides

Full Text Available Gastrointestinal (GI parasitic infection is the main health constraint for small ruminant production, causing loss of weight and/or death. Red Maasai sheep have adapted to a tropical environment where extreme parasite exposure is a constant, especially with highly pathogenic Haemonchus contortus. This breed has been reported to be resistant to gastrointestinal parasite infection, hence it is considered an invaluable resource to study associations between host genetics and resistance. The aim of this study was to identify polymorphisms strongly associated with host resistance in a double backcross population derived from Red Maasai and Dorper sheep using a SNP-based GWAS analysis. The animals that were genotyped represented the most resistant and susceptible individuals based on the tails of phenotypic distribution (10% each for average faecal egg counts (AVFEC. AVFEC, packed cell volume (AVPCV, and live weight (AVLWT were adjusted for fixed effects and co-variables, and an association analysis was run using EMMAX. Revised significance levels were calculated using 100,000 permutation tests. The top five significant SNP markers with - log10 p-values >3.794 were observed on five different chromosomes for AVFEC, and BLUPPf90/PostGSf90 results confirmed EMMAX significant regions for this trait. One of these regions included a cluster of significant SNP on chromosome (Chr 6 not in linkage disequilibrium to each other. This genomic location contains annotated genes involved in cytokine signalling, haemostasis and mucus biosynthesis. Only one association detected on Chr 7 was significant for both AVPCV and AVLWT. The results generated here reveal candidate immune variants for genes involved in differential response to infection and provide additional SNP marker information that has potential to aid selection of resistance to gastrointestinal parasites in sheep of a similar genetic background to the double backcross population.

Profile of peripheral blood neutrophil cytokines in diabetes type 1 pregnant women and its correlation with selected parameters in the newborns.

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Pertyńska-Marczewska, Magdalena; Głowacka, Ewa; Grodzicka, Alicja; Sobczak, Małgorzata; Cypryk, Katarzyna; Wilczyński, Jacek R; Wilczyński, Jan

2010-02-01

Interleukin (IL)-12, IL-10, tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 alter as pregnancy progresses, implying continuous immune regulation associated with the maintenance of pregnancy. We aimed to evaluate the peripheral blood neutrophil-derived production of these cytokines in the course of pregnancy complicated by type 1 diabetes. of study These parameters were measured in samples from healthy non-pregnant (C), diabetic non-pregnant (D), healthy pregnant (P) and pregnant diabetic (PD) women. Neutrophil-derived secretion of TNF-alpha and IL-12 increased along with progression of pregnancy in PD and P groups. The concentration of IL-10 from lipopolysaccharide (LPS)-stimulated neutrophils increased during the course of uncomplicated pregnancy but decreased in diabetic pregnancy. Concentration of IL-8 decreased with the advancing gestational age in P and PD groups. LPS-stimulated neutrophil-derived IL-6 concentration increased only in PD patients. Our results show that diabetes creates pro-inflammatory environment thus potentially influencing the outcome of pregnancy. We conclude that neutrophil-derived cytokine production could contribute to the complications seen in pregnant women with type 1 diabetes.

Transcription factors ETF, E2F, and SP-1 are involved in cytokine-independent proliferation of murine hepatocytes.

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Zellmer, Sebastian; Schmidt-Heck, Wolfgang; Godoy, Patricio; Weng, Honglei; Meyer, Christoph; Lehmann, Thomas; Sparna, Titus; Schormann, Wiebke; Hammad, Seddik; Kreutz, Clemens; Timmer, Jens; von Weizsäcker, Fritz; Thürmann, Petra A; Merfort, Irmgard; Guthke, Reinhard; Dooley, Steven; Hengstler, Jan G; Gebhardt, Rolf

2010-12-01

The cellular basis of liver regeneration has been intensely investigated for many years. However, the mechanisms initiating hepatocyte "plasticity" and priming for proliferation are not yet fully clear. We investigated alterations in gene expression patterns during the first 72 hours of C57BL/6N mouse hepatocyte culture on collagen monolayers (CM), which display a high basal frequency of proliferation in the absence of cytokines. Although many metabolic genes were down-regulated, genes related to mitogen-activated protein kinase (MAPK) signaling and cell cycle were up-regulated. The latter genes showed an overrepresentation of transcription factor binding sites (TFBS) for ETF (TEA domain family member 2), E2F1 (E2F transcription factor 1), and SP-1 (Sp1 transcription factor) (P ETF, E2F1, and SP-1 and displayed increased expression of E2F1. Cultivation of murine hepatocytes on CM primes cells for proliferation through cytokine-independent activation of MAPK signaling. The transcription factors ETF, E2F1, and SP-1 seem to play a pronounced role in mediating proliferation-dependent differential gene expression. Similar events, but on a shorter time-scale, occur very early after liver damage in vivo. Copyright © 2010 American Association for the Study of Liver Diseases.

Membrane-Wrapping Contributions to Malaria Parasite Invasion of the Human Erythrocyte

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Dasgupta, Sabyasachi; Auth, Thorsten; Gov, Nir S.; Satchwell, Timothy J.; Hanssen, Eric; Zuccala, Elizabeth S.; Riglar, David T.; Toye, Ashley M.; Betz, Timo; Baum, Jake; Gompper, Gerhard

2014-01-01

The blood stage malaria parasite, the merozoite, has a small window of opportunity during which it must successfully target and invade a human erythrocyte. The process of invasion is nonetheless remarkably rapid. To date, mechanistic models of invasion have focused predominantly on the parasite actomyosin motor contribution to the energetics of entry. Here, we have conducted a numerical analysis using dimensions for an archetypal merozoite to predict the respective contributions of the host-parasite interactions to invasion, in particular the role of membrane wrapping. Our theoretical modeling demonstrates that erythrocyte membrane wrapping alone, as a function of merozoite adhesive and shape properties, is sufficient to entirely account for the first key step of the invasion process, that of merozoite reorientation to its apex and tight adhesive linkage between the two cells. Next, parasite-induced reorganization of the erythrocyte cytoskeleton and release of parasite-derived membrane can also account for a considerable energetic portion of actual invasion itself, through membrane wrapping. Thus, contrary to the prevailing dogma, wrapping by the erythrocyte combined with parasite-derived membrane release can markedly reduce the expected contributions of the merozoite actomyosin motor to invasion. We therefore propose that invasion is a balance between parasite and host cell contributions, evolved toward maximal efficient use of biophysical forces between the two cells. PMID:24988340

Cytokines and the anorexia of infection: potential mechanisms and treatments.

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McCarthy, D O

2000-04-01

Anorexia during infection is thought to be mediated by immunoregulatory cytokines such as interleukins 1 and 6 and tumor necrosis factor. This article reviews the potential mechanisms of action by which these cytokines are thought to suppress food intake during infection and examines the proposition that blocking of cytokine activity might be one approach to improving food intake of the infected host.

African origin of the malaria parasite Plasmodium vivax.

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Liu, Weimin; Li, Yingying; Shaw, Katharina S; Learn, Gerald H; Plenderleith, Lindsey J; Malenke, Jordan A; Sundararaman, Sesh A; Ramirez, Miguel A; Crystal, Patricia A; Smith, Andrew G; Bibollet-Ruche, Frederic; Ayouba, Ahidjo; Locatelli, Sabrina; Esteban, Amandine; Mouacha, Fatima; Guichet, Emilande; Butel, Christelle; Ahuka-Mundeke, Steve; Inogwabini, Bila-Isia; Ndjango, Jean-Bosco N; Speede, Sheri; Sanz, Crickette M; Morgan, David B; Gonder, Mary K; Kranzusch, Philip J; Walsh, Peter D; Georgiev, Alexander V; Muller, Martin N; Piel, Alex K; Stewart, Fiona A; Wilson, Michael L; Pusey, Anne E; Cui, Liwang; Wang, Zenglei; Färnert, Anna; Sutherland, Colin J; Nolder, Debbie; Hart, John A; Hart, Terese B; Bertolani, Paco; Gillis, Amethyst; LeBreton, Matthew; Tafon, Babila; Kiyang, John; Djoko, Cyrille F; Schneider, Bradley S; Wolfe, Nathan D; Mpoudi-Ngole, Eitel; Delaporte, Eric; Carter, Richard; Culleton, Richard L; Shaw, George M; Rayner, Julian C; Peeters, Martine; Hahn, Beatrice H; Sharp, Paul M

2014-01-01

Plasmodium vivax is the leading cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its receptor, the Duffy antigen, on human erythrocytes. The emergence of this protective allele is not understood because P. vivax is believed to have originated in Asia. Here we show, using a non-invasive approach, that wild chimpanzees and gorillas throughout central Africa are endemically infected with parasites that are closely related to human P. vivax. Sequence analyses reveal that ape parasites lack host specificity and are much more diverse than human parasites, which form a monophyletic lineage within the ape parasite radiation. These findings indicate that human P. vivax is of African origin and likely selected for the Duffy-negative mutation. All extant human P. vivax parasites are derived from a single ancestor that escaped out of Africa.

African origin of the malaria parasite Plasmodium vivax

Science.gov (United States)

Liu, Weimin; Li, Yingying; Shaw, Katharina S.; Learn, Gerald H.; Plenderleith, Lindsey J.; Malenke, Jordan A.; Sundararaman, Sesh A.; Ramirez, Miguel A.; Crystal, Patricia A.; Smith, Andrew G.; Bibollet-Ruche, Frederic; Ayouba, Ahidjo; Locatelli, Sabrina; Esteban, Amandine; Mouacha, Fatima; Guichet, Emilande; Butel, Christelle; Ahuka-Mundeke, Steve; Inogwabini, Bila-Isia; Ndjango, Jean-Bosco N.; Speede, Sheri; Sanz, Crickette M.; Morgan, David B.; Gonder, Mary K.; Kranzusch, Philip J.; Walsh, Peter D.; Georgiev, Alexander V.; Muller, Martin N.; Piel, Alex K.; Stewart, Fiona A.; Wilson, Michael L.; Pusey, Anne E.; Cui, Liwang; Wang, Zenglei; Färnert, Anna; Sutherland, Colin J.; Nolder, Debbie; Hart, John A.; Hart, Terese B.; Bertolani, Paco; Gillis, Amethyst; LeBreton, Matthew; Tafon, Babila; Kiyang, John; Djoko, Cyrille F.; Schneider, Bradley S.; Wolfe, Nathan D.; Mpoudi-Ngole, Eitel; Delaporte, Eric; Carter, Richard; Culleton, Richard L.; Shaw, George M.; Rayner, Julian C.; Peeters, Martine; Hahn, Beatrice H.; Sharp, Paul M.

2014-01-01

Plasmodium vivax is the leading cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its receptor, the Duffy antigen, on human erythrocytes. The emergence of this protective allele is not understood because P. vivax is believed to have originated in Asia. Here we show, using a non-invasive approach, that wild chimpanzees and gorillas throughout central Africa are endemically infected with parasites that are closely related to human P. vivax. Sequence analyses reveal that ape parasites lack host specificity and are much more diverse than human parasites, which form a monophyletic lineage within the ape parasite radiation. These findings indicate that human P. vivax is of African origin and likely selected for the Duffy-negative mutation. All extant human P. vivax parasites are derived from a single ancestor that escaped out of Africa. PMID:24557500

The role of growth factors in maintenance of stemness in bone marrow-derived mesenchymal stem cells

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Eom, Young Woo; Oh, Ji-Eun [Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Lee, Jong In [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Baik, Soon Koo [Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Department of Internal Medicine, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Rhee, Ki-Jong [Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei Univ., Wonju (Korea, Republic of); Shin, Ha Cheol; Kim, Yong Man [Pharmicell Co., Ltd., Sungnam (Korea, Republic of); Ahn, Chan Mug [Department of Basic Science, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Kong, Jee Hyun [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Kim, Hyun Soo, E-mail: khsmd@pharmicell.com [Pharmicell Co., Ltd., Sungnam (Korea, Republic of); Shim, Kwang Yong, E-mail: kyshim@yonsei.ac.kr [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of)

2014-02-28

Highlights: • Expression of FGF-2, FGF-4, EGF, and HGF decreased during long-term culture of BMSCs. • Loss of growth factors induced autophagy, senescence and decrease of stemness. • FGF-2 increased proliferation potential via AKT and ERK activation in BMSCs. • FGF-2 suppressed LC3-II expression and down-regulated senescence of BMSCs. • HGF was important in maintenance of the differentiation potential of BMSCs. - Abstract: Mesenchymal stem cells (MSCs) are an active topic of research in regenerative medicine due to their ability to secrete a variety of growth factors and cytokines that promote healing of damaged tissues and organs. In addition, these secreted growth factors and cytokines have been shown to exert an autocrine effect by regulating MSC proliferation and differentiation. We found that expression of EGF, FGF-4 and HGF were down-regulated during serial passage of bone marrow-derived mesenchymal stem cells (BMSCs). Proliferation and differentiation potentials of BMSCs treated with these growth factors for 2 months were evaluated and compared to BMSCs treated with FGF-2, which increased proliferation of BMSCs. FGF-2 and -4 increased proliferation potentials at high levels, about 76- and 26-fold, respectively, for 2 months, while EGF and HGF increased proliferation of BMSCs by less than 2.8-fold. Interestingly, differentiation potential, especially adipogenesis, was maintained only by HGF treatment. Treatment with FGF-2 rapidly induced activation of AKT and later induced ERK activation. The basal level of phosphorylated ERK increased during serial passage of BMSCs treated with FGF-2. The expression of LC3-II, an autophagy marker, was gradually increased and the population of senescent cells was increased dramatically at passage 7 in non-treated controls. But FGF-2 and FGF-4 suppressed LC3-II expression and down-regulated senescent cells during long-term (i.e. 2 month) cultures. Taken together, depletion of growth factors during serial passage

The role of growth factors in maintenance of stemness in bone marrow-derived mesenchymal stem cells

International Nuclear Information System (INIS)

Eom, Young Woo; Oh, Ji-Eun; Lee, Jong In; Baik, Soon Koo; Rhee, Ki-Jong; Shin, Ha Cheol; Kim, Yong Man; Ahn, Chan Mug; Kong, Jee Hyun; Kim, Hyun Soo; Shim, Kwang Yong

2014-01-01

Highlights: • Expression of FGF-2, FGF-4, EGF, and HGF decreased during long-term culture of BMSCs. • Loss of growth factors induced autophagy, senescence and decrease of stemness. • FGF-2 increased proliferation potential via AKT and ERK activation in BMSCs. • FGF-2 suppressed LC3-II expression and down-regulated senescence of BMSCs. • HGF was important in maintenance of the differentiation potential of BMSCs. - Abstract: Mesenchymal stem cells (MSCs) are an active topic of research in regenerative medicine due to their ability to secrete a variety of growth factors and cytokines that promote healing of damaged tissues and organs. In addition, these secreted growth factors and cytokines have been shown to exert an autocrine effect by regulating MSC proliferation and differentiation. We found that expression of EGF, FGF-4 and HGF were down-regulated during serial passage of bone marrow-derived mesenchymal stem cells (BMSCs). Proliferation and differentiation potentials of BMSCs treated with these growth factors for 2 months were evaluated and compared to BMSCs treated with FGF-2, which increased proliferation of BMSCs. FGF-2 and -4 increased proliferation potentials at high levels, about 76- and 26-fold, respectively, for 2 months, while EGF and HGF increased proliferation of BMSCs by less than 2.8-fold. Interestingly, differentiation potential, especially adipogenesis, was maintained only by HGF treatment. Treatment with FGF-2 rapidly induced activation of AKT and later induced ERK activation. The basal level of phosphorylated ERK increased during serial passage of BMSCs treated with FGF-2. The expression of LC3-II, an autophagy marker, was gradually increased and the population of senescent cells was increased dramatically at passage 7 in non-treated controls. But FGF-2 and FGF-4 suppressed LC3-II expression and down-regulated senescent cells during long-term (i.e. 2 month) cultures. Taken together, depletion of growth factors during serial passage

Plasticity of regulatory T cells under cytokine pressure.

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Diaconu, Carmen C; Neagu, Ana I; Lungu, Răzvan; Tardei, Graţiela; Alexiu, Irina; Bleotu, Coralia; Economescu, Mihaela Chivu; Bumbăcea, Roxana S; Pele, Irina; Bumbăcea, Dragoş

2010-01-01

CD4+ T helper (Th) cells have been divided into different subsets as defined by their cytokine products and functions after their activation. CD4+ T cell subsets are continuously discovered and until now Th1, Th2, Th9, Th17, and regulatory T (Treg) cells have been almost unanimously recognized but yet not completely characterized. The selective production of cytokines by each of the subsets is probably the master key of the mechanisms of immune regulation. The cytokine milieu is extremely important on deciding the fate of T cells. Generally, more than one cytokine is needed for differentiating to a particular lineage and just recently it was shown that this status quo of commitment could be challenged. It is well known that cytokines bind to Type I/II cytokine receptors signaling via Janus kinases (JAKs) followed by activation of Signal Transducer and Activator of Transcription (STAT). STAT molecules work together with other transcription factors (Foxp3, RORgammat and RORalpha, T-bet, GATA3, Runx 1, NFAT, etc.) also controlled by cytokines, in modulating the Th phenotype and functions. In this review, we analyze the plasticity of Treg population focusing on the most recent discoveries on how microenvironmental cytokines refine/modify Treg phenotype and function, thus changing their fate.

Vagotomy attenuates brain cytokines and sleep induced by peripherally administered tumor necrosis factor-α and lipopolysaccharide in mice.

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Zielinski, Mark R; Dunbrasky, Danielle L; Taishi, Ping; Souza, Gianne; Krueger, James M

2013-08-01

Systemic tumor necrosis factor-α (TNF-α) is linked to sleep and sleep altering pathologies in humans. Evidence from animals indicates that systemic and brain TNF-α have a role in regulating sleep. In animals, TNF-α or lipopolysaccharide (LPS) enhance brain pro-inflammatory cytokine expression and sleep after central or peripheral administration. Vagotomy blocks enhanced sleep induced by systemic TNF-α and LPS in rats, suggesting that vagal afferent stimulation by TNF-α enhances pro-inflammatory cytokines in sleep-related brain areas. However, the effects of systemic TNF-α on brain cytokine expression and mouse sleep remain unknown. We investigated the role of vagal afferents on brain cytokines and sleep after systemically applied TNF-α or LPS in mice. Spontaneous sleep was similar in vagotomized and sham-operated controls. Vagotomy attenuated TNF-α- and LPS-enhanced non-rapid eye movement sleep (NREMS); these effects were more evident after lower doses of these substances. Vagotomy did not affect rapid eye movement sleep responses to these substances. NREMS electroencephalogram delta power (0.5-4 Hz range) was suppressed after peripheral TNF-α or LPS injections, although vagotomy did not affect these responses. Compared to sham-operated controls, vagotomy did not affect liver cytokines. However, vagotomy attenuated interleukin-1 beta (IL-1β) and TNF-α mRNA brain levels after TNF-α, but not after LPS, compared to the sham-operated controls. We conclude that vagal afferents mediate peripheral TNF-α-induced brain TNF-α and IL-1β mRNA expressions to affect sleep. We also conclude that vagal afferents alter sleep induced by peripheral pro-inflammatory stimuli in mice similar to those occurring in other species.

Prevalence and correlation of cytokine-specific autoantibodies with epidemiological factors and C-reactive protein in 8,972 healthy individuals

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von Stemann, Jakob Hjorth; Rigas, Andreas Stribolt; Thørner, Lise Wegner

2017-01-01

Natural cytokine-specific autoantibodies (c-aAb) have been measured in healthy and diseased individuals, and have been considered as both endogenous immune-regulators and pathogenic factors. Overall, the etiology and potential pathology of c-aAb are still undefined. To further characterize the sero...

Prostaglandin E2 and Transforming Growth Factor-β Play a Critical Role in Suppression of Allergic Airway Inflammation by Adipose-Derived Stem Cells.

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Kyu-Sup Cho

Full Text Available The role of soluble factors in the suppression of allergic airway inflammation by adipose-derived stem cells (ASCs remains to be elucidated. Moreover, the major soluble factors responsible for the immunomodulatory effects of ASCs in allergic airway diseases have not been well documented. We evaluated the effects of ASCs on allergic inflammation in asthmatic mice treated with a prostaglandin E2 (PGE2 inhibitor or transforming growth factor-β (TGF-β neutralizing antibodies.Asthmatic mice were injected intraperitoneally with a PGE2 inhibitor or TGF-β neutralizing antibodies at approximately the same time as ASCs injection and were compared with non-treated controls. In asthmatic mice, ASCs significantly reduced airway hyperresponsiveness, the number of total inflammatory cells and eosinophils in the bronchoalveolar lavage fluid (BALF, eosinophilic inflammation, goblet cell hyperplasia, and serum total and allergen-specific IgE and IgG1. ASCs significantly inhibited Th2 cytokines, such as interleukin (IL-4, IL-5, and IL-13, and enhanced the Th1 cytokine (Interferon-γ and regulatory cytokines (IL-10 and TGF-β in the BALF and lung draining lymph nodes (LLNs. ASCs engraftment caused significant increases in the regulatory T cell (Treg and IL-10+ T cell populations in LLNs. However, blocking PGE2 or TGF-β eliminated the immunosuppressive effect of ASCs in allergic airway inflammation.ASCs are capable of secreting PGE2 and TGF-β, which may play a role in inducing Treg expansion. Furthermore, treatment with a PGE2 inhibitor or TGF-β neutralizing antibodies eliminated the beneficial effect of ASCs treatment in asthmatic mice, suggesting that PGE2 and TGF-β are the major soluble factors responsible for suppressing allergic airway inflammation.

The role of cytokine deficiencies and cytokine autoantibodies in clinical dermatology

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Liszewski, Walter; Gniadecki, Robert

2016-01-01

due to a downregulation or absence of cytokines. Here, we review the diagnosis and clinical management of cytokine deficiency syndromes in dermatology. We will review the biology of cytokines, and the current approved indications for recombinant cytokines and anticytokine antibodies. We will also...

Modulation of Female Genital Tract-Derived Dendritic Cell Migration and Activation in Response to Inflammatory Cytokines and Toll-Like Receptor Agonists.

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Muki S Shey

Full Text Available HIV transmission across the genital mucosa is a major mode of new HIV infections in women. The probability of infection may be influenced by several factors including recruitment and activation of HIV target cells, such as dendritic cells (DCs and cytokine production, associated with genital inflammation. We evaluated the role of inflammatory cytokines and TLR signaling in migration and activation of genital tract DCs in the human cervical explant model. Hysterectomy tissues from 10 HIV-negative and 7 HIV-positive donor women were separated into ecto- and endocervical explants, and incubated with inflammatory cytokines (TNF-α, IL-1β, IL-8, MIP-1β or agonists for TLR4 (LPS, TLR2/1 (PAM3 and TLR7/8 (R848. Migration (frequency and activation (HLA-DR expression of myeloid and plasmacytoid DCs and Langerhans cells were measured by flow cytometry. We observed that cytokines, LPS and PAM3 induced activation of migrating myeloid and plasmacytoid DCs. LPS induced a 3.6 fold lower levels of migration of plasmacytoid DCs from HIV-infected women compared with HIV-uninfected women (median activation indices of 2.932 vs 0.833. There was however a 4.5 fold increase in migration of Langerhans cells in HIV-infected compared with HIV-uninfected women in response to cytokines (median activation indices of 3.539 vs 0.77. Only TLR agonists induced migration and activation of DCs from endocervical explants. Hormonal contraception use was associated with an increase in activation of DC subsets in the endo and ectocervical explants. We conclude that inflammatory signals in the female genital tract induced DC migration and activation, with possible important implications for HIV susceptibility of cervical tissues.

Stimulation of neurotrophic factors and inhibition of proinflammatory cytokines by exogenous application of triiodothyronine in the rat model of ischemic stroke.

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Sabbaghziarani, Fatemeh; Mortezaee, Keywan; Akbari, Mohammad; Kashani, Iraj Ragerdi; Soleimani, Mansooreh; Hassanzadeh, Gholamreza; Zendedel, Adib

2017-01-01

There is a positive relation between decreases of triiodothyronine (T3) amounts and severity of stroke. The aim of this study was to evaluate the effect of exogenous T3 application on levels of neurogenesis markers in the subventricular zone. Cerebral ischemia was induced by middle cerebral artery occlusion in male Wistar rats. There were 4 experimental groups: sham, ischemic, vehicle, and treatment. Rats were injected with T3 (25 μg/kg, IV injection) at 24 hours after ischemia. Animals were sacrificed at day 7 after ischemia. There were high levels of brain-derived neurotrophic factor, nestin, and Sox2 expressions in gene and protein levels in the T3 treatment group (P ≤ .05 vs ischemic group). Treatment group showed high levels of sera T3 and thyroxine (T4) but low levels of thyrotropin (TSH), tumor necrosis factor-α, and interleukin-6 (P ≤ .05 vs ischemic group) at day 4 after ischemia induction. Findings of this study revealed the effectiveness of exogenous T3 application in the improvement of neurogenesis possibly via regulation of proinflammatory cytokines. Copyright © 2017 John Wiley & Sons, Ltd.

Release kinetics of platelet-derived and plasma-derived growth factors from autologous plasma rich in growth factors.

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Anitua, Eduardo; Zalduendo, Mari Mar; Alkhraisat, Mohammad Hamdan; Orive, Gorka

2013-10-01

Many studies have evaluated the biological effects of platelet rich plasma reporting the final outcomes on cell and tissues. However, few studies have dealt with the kinetics of growth factor delivery by plasma rich in growth factors. Venous blood was obtained from three healthy volunteers and processed with PRGF-Endoret technology to prepare autologous plasma rich in growth factors. The gel-like fibrin scaffolds were then incubated in triplicate, in a cell culture medium to monitor the release of PDGF-AB, VEGF, HGF and IGF-I during 8 days of incubation. A leukocyte-platelet rich plasma was prepared employing the same technology and the concentrations of growth factors and interleukin-1β were determined after 24h of incubation. After each period, the medium was collected, fibrin clot was destroyed and the supernatants were stored at -80°C until analysis. The growth factor delivery is diffusion controlled with a rapid initial release by 30% of the bioactive content after 1h of incubation and a steady state release when almost 70% of the growth factor content has been delivered. Autologous fibrin matrix retained almost 30% of the amount of the growth factors after 8 days of incubation. The addition of leukocytes to the formula of platelet rich plasma did not increase the concentration of the growth factors, while it drastically increased the presence of pro-inflammatory IL-1β. Further studies employing an in vitro inflammatory model would be interesting to study the difference in growth factors and pro-inflammatory cytokines between leukocyte-free and leukocyte-rich platelet rich plasma. Copyright © 2013 Elsevier GmbH. All rights reserved.

Dose-rate effects of protons on in vivo activation of nuclear factor-kappa B and cytokines in mouse bone marrow cells

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Rithidech, K.N.; Rusek, A.; Reungpatthanaphong, P.; Honikel, L.; Simon, S.R.

2010-05-28

The objective of this study was to determine the kinetics of nuclear factor-kappa B (NF-{kappa}B) activation and cytokine expression in bone marrow (BM) cells of exposed mice as a function of the dose rate of protons. The cytokines included in this study are pro-inflammatory [i.e., tumor necrosis factor-alpha (TNF-{alpha}), interleukin-1beta (IL-1{beta}), and IL-6] and anti-inflammatory cytokines (i.e., IL-4 and IL-10). We gave male BALB/cJ mice a whole-body exposure to 0 (sham-controls) or 1.0 Gy of 100 MeV protons, delivered at 5 or 10 mGy min{sup -1}, the dose and dose rates found during solar particle events in space. As a reference radiation, groups of mice were exposed to 0 (sham-controls) or 1 Gy of {sup 137}Cs {gamma} rays (10 mGy min{sup -1}). After irradiation, BM cells were collected at 1.5, 3, 24 h, and 1 month for analyses (five mice per treatment group per harvest time). The results indicated that the in vivo time course of effects induced by a single dose of 1 Gy of 100 MeV protons or {sup 137}Cs {gamma} rays, delivered at 10 mGy min{sup -1}, was similar. Although statistically significant levels of NF-{kappa}B activation and pro-inflammatory cytokines in BM cells of exposed mice when compared to those in the corresponding sham controls (Student's t-test, p < 0.05 or < 0.01) were induced by either dose rate, these levels varied over time for each protein. Further, only a dose rate of 5 mGy min{sup -1} induced significant levels of anti-inflammatory cytokines. The results indicate dose-rate effects of protons.

Proinflammatory cytokines in open versus laparoscopic cholecystectomy

International Nuclear Information System (INIS)

Abu-Eshy, Saeed A.; Al-Rofaidi, Abdallah A.; Al-Faki, Ahmed S.; Ghalib, Hashim W.; Moosa, Riyadh A.; Sadik, Ali A.; Salati, Mohammad I.

2002-01-01

Laparoscopic cholecystectomy, a minimal access surgery, is fast replacing open cholecystectomy and is being associated with less trauma. The objective of this study was to compare the proinflammatory cytokine levels in both laparoscopic cholecystectomy and open cholecystectomy. This study was carried out at Aseer Central Hospital, Aseer region, Abha Private Hospital and the College of Medicine and Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia, during the time period October 1998 through to November 2000. Sixty-one patients were included in the study, 27 of them had laparoscopic cholecystectomy and 34 had open cholecystectomy. Cytokines [Interleukin-6 Interleukin-1b, Tumor necrosis factor -a and Interleukin- 8] were measured in blood samples collected from the patients before, at and 24 hours post surgery, using commercially available kits. Interleukin-6 levels were significantly increased at 24 hours post surgery in the open cholecystectomy group of patients compared to the laparoscopic cholecystectomy group (P<0.04). No differences were found in the other cytokines levels (Interleukin-1b, tumor necrosis factor -a and Interleukin-8) between the open cholecystectomy and laparoscopic cholecystectomy groups. Laparoscopic cholecystectomy, a minimal access surgery, is associated with lower levels of the proinflammatory interleukin-6 cytokine compared to open cholecystectomy. (author)

Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum.

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Brancucci, Nicolas M B; Gerdt, Joseph P; Wang, ChengQi; De Niz, Mariana; Philip, Nisha; Adapa, Swamy R; Zhang, Min; Hitz, Eva; Niederwieser, Igor; Boltryk, Sylwia D; Laffitte, Marie-Claude; Clark, Martha A; Grüring, Christof; Ravel, Deepali; Blancke Soares, Alexandra; Demas, Allison; Bopp, Selina; Rubio-Ruiz, Belén; Conejo-Garcia, Ana; Wirth, Dyann F; Gendaszewska-Darmach, Edyta; Duraisingh, Manoj T; Adams, John H; Voss, Till S; Waters, Andrew P; Jiang, Rays H Y; Clardy, Jon; Marti, Matthias

2017-12-14

Transmission represents a population bottleneck in the Plasmodium life cycle and a key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective to the mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that the host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by repressing parasite sexual differentiation. We demonstrate that exogenous LysoPC drives biosynthesis of the essential membrane component phosphatidylcholine. LysoPC restriction induces a compensatory response, linking parasite metabolism to the activation of sexual-stage-specific transcription and gametocyte formation. Our results reveal that malaria parasites can sense and process host-derived physiological signals to regulate differentiation. These data close a critical knowledge gap in parasite biology and introduce a major component of the sexual differentiation pathway in Plasmodium that may provide new approaches for blocking malaria transmission. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Host Diet Affects the Morphology of Monarch Butterfly Parasites.

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Hoang, Kevin; Tao, Leiling; Hunter, Mark D; de Roode, Jacobus C

2017-06-01

Understanding host-parasite interactions is essential for ecological research, wildlife conservation, and health management. While most studies focus on numerical traits of parasite groups, such as changes in parasite load, less focus is placed on the traits of individual parasites such as parasite size and shape (parasite morphology). Parasite morphology has significant effects on parasite fitness such as initial colonization of hosts, avoidance of host immune defenses, and the availability of resources for parasite replication. As such, understanding factors that affect parasite morphology is important in predicting the consequences of host-parasite interactions. Here, we studied how host diet affected the spore morphology of a protozoan parasite ( Ophryocystis elektroscirrha ), a specialist parasite of the monarch butterfly ( Danaus plexippus ). We found that different host plant species (milkweeds; Asclepias spp.) significantly affected parasite spore size. Previous studies have found that cardenolides, secondary chemicals in host plants of monarchs, can reduce parasite loads and increase the lifespan of infected butterflies. Adding to this benefit of high cardenolide milkweeds, we found that infected monarchs reared on milkweeds of higher cardenolide concentrations yielded smaller parasites, a potentially hidden characteristic of cardenolides that may have important implications for monarch-parasite interactions.

School-based prevalence of intestinal parasitic infections and associated risk factors in rural communities of Sana'a, Yemen.

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Al-Mekhlafi, Abdulsalam M; Abdul-Ghani, Rashad; Al-Eryani, Samira M; Saif-Ali, Reyadh; Mahdy, Mohammed A K

2016-11-01

Yemen is a developing country overwhelmed with a triad of poverty, diseases and social conflicts. Moreover, the majority of its population live in rural communities and suffer from intestinal parasitic infections (IPIs). Therefore, the present school-based, cross-sectional survey aimed to detect the prevalence of such infections and associated risk factors among schoolchildren in the rural communities of Bani Alharith, Hamdan and Bani Hushaysh districts of Sana'a, north of Yemen. Socio-demographic data and certain behavioral risk factors as well as stool samples were collected from 1218 schoolchildren from ten randomly schools in the study area. Fresh stool samples were examined for parasites by direct saline and iodine preparations and after concentration with formol-ether technique. The overall prevalence of IPIs was 54.8%, with a higher frequency of protozoal than helminthic infections (37.6 vs. 17.2%, respectively). Parasite species recovered were Entameba histolytica (21.5%), Giardia lamblia (16.1%), Ascaris lumbricoides (8.3%), Hymenolepis nana (5.3%), Schistosoma mansoni (2.6%), Trichuris trichiura (0.5%) and Enterobius vermicularis (0.4%). Univariate analysis showed that the male gender and illiteracy of fathers and/or mothers were the socio-demographic factors significantly associated with higher infection rates. The illiteracy of mothers was also confirmed as an independent risk factor by multivariable analysis. On the other hand, not washing hands before eating, not washing fruits and vegetables before consumption, eating uncovered food and not clipping fingernails were the risk behaviors significantly associated with higher infection rates, with the last three ones being confirmed as independent risk factors. Therefore, control measures should include regular treatment of protozoal infections and deworming of schoolchildren, promotion of hygiene in rural schools through health education programs, regular inspection of schoolchildren for personal hygiene

Parasite load and risk factors for poor outcome among children with visceral leishmaniasis. A cohort study in Belo Horizonte, Brazil, 2010-2011

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Maria Vitória Assumpção Mourão

2014-04-01

Full Text Available Clinical and laboratory risk factors for death from visceral leishmaniasis (VL are relatively known, but quantitative real-time polymerase chain reaction (qPCR might assess the role of parasite load in determining clinical outcome. The aim of this study was to identify risk factors, including parasite load in peripheral blood, for VL poor outcome among children. This prospective cohort study evaluated children aged ≤ 12 years old with VL diagnosis at three times: pre-treatment (T0, during treatment (T1 and post-treatment (T2. Forty-eight patients were included and 16 (33.3% met the criteria for poor outcome. Age ≤ 12 months [relative risk (RR 3.51; 95% confidence interval (CI 1.89-6.52], tachydyspnoea (RR 3.46; 95% CI 2.19-5.47, bacterial infection (RR 3.08; 95% CI 1.27-7.48, liver enlargement (RR 3.00; 95% CI 1.44-6.23 and low serum albumin (RR 7.00; 95% CI 1.80-27.24 were identified as risk factors. qPCR was positive in all patients at T0 and the parasite DNA was undetectable in 76.1% of them at T1 and in 90.7% at T2. There was no statistical association between parasite load at T0 and poor outcome.

Biophysics of malarial parasite exit from infected erythrocytes.

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Chandramohanadas, Rajesh; Park, YongKeun; Lui, Lena; Li, Ang; Quinn, David; Liew, Kingsley; Diez-Silva, Monica; Sung, Yongjin; Dao, Ming; Lim, Chwee Teck; Preiser, Peter Rainer; Suresh, Subra

2011-01-01

Upon infection and development within human erythrocytes, P. falciparum induces alterations to the infected RBC morphology and bio-mechanical properties to eventually rupture the host cells through parasitic and host derived proteases of cysteine and serine families. We used previously reported broad-spectrum inhibitors (E64d, EGTA-AM and chymostatin) to inhibit these proteases and impede rupture to analyze mechanical signatures associated with parasite escape. Treatment of late-stage iRBCs with E64d and EGTA-AM prevented rupture, resulted in no major RBC cytoskeletal reconfiguration but altered schizont morphology followed by dramatic re-distribution of three-dimensional refractive index (3D-RI) within the iRBC. These phenotypes demonstrated several-fold increased iRBC membrane flickering. In contrast, chymostatin treatment showed no 3D-RI changes and caused elevated fluctuations solely within the parasitophorous vacuole. We show that E64d and EGTA-AM supported PV breakdown and the resulting elevated fluctuations followed non-Gaussian pattern that resulted from direct merozoite impingement against the iRBC membrane. Optical trapping experiments highlighted reduced deformability of the iRBC membranes upon rupture-arrest, more specifically in the treatments that facilitated PV breakdown. Taken together, our experiments provide novel mechanistic interpretations on the role of parasitophorous vacuole in maintaining the spherical schizont morphology, the impact of PV breakdown on iRBC membrane fluctuations leading to eventual parasite escape and the evolution of membrane stiffness properties of host cells in which merozoites were irreversibly trapped, recourse to protease inhibitors. These findings provide a comprehensive, previously unavailable, body of information on the combined effects of biochemical and biophysical factors on parasite egress from iRBCs.

Spatial structures in a simple model of population dynamics for parasite-host interactions

Energy Technology Data Exchange (ETDEWEB)

Dong, J. J.; Skinner, B.; Breecher, N.; Schmittmann, B.; Zia, R. K. P.

2015-08-01

Spatial patterning can be crucially important for understanding the behavior of interacting populations. Here we investigate a simple model of parasite and host populations in which parasites are random walkers that must come into contact with a host in order to reproduce. We focus on the spatial arrangement of parasites around a single host, and we derive using analytics and numerical simulations the necessary conditions placed on the parasite fecundity and lifetime for the populations long-term survival. We also show that the parasite population can be pushed to extinction by a large drift velocity, but, counterintuitively, a small drift velocity generally increases the parasite population.

Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

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Xiong, H.; Yang, X.Y.; Han, J.; Wang, Q.; Zou, Z.L. [Department of Hematology, Shanghai Clinical Research Center, Chinese Academy of Sciences, Shanghai Xuhui District Central Hospital, Shanghai (China)

2015-01-20

The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS.

Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

International Nuclear Information System (INIS)

Xiong, H.; Yang, X.Y.; Han, J.; Wang, Q.; Zou, Z.L.

2015-01-01

The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS

Role of transposon-derived small RNAs in the interplay between genomes and parasitic DNA in rice.

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Misuzu Nosaka

2012-09-01

Full Text Available RNA silencing is a defense system against "genomic parasites" such as transposable elements (TE, which are potentially harmful to host genomes. In plants, transcripts from TEs induce production of double-stranded RNAs (dsRNAs and are processed into small RNAs (small interfering RNAs, siRNAs that suppress TEs by RNA-directed DNA methylation. Thus, the majority of TEs are epigenetically silenced. On the other hand, most of the eukaryotic genome is composed of TEs and their remnants, suggesting that TEs have evolved countermeasures against host-mediated silencing. Under some circumstances, TEs can become active and increase in copy number. Knowledge is accumulating on the mechanisms of TE silencing by the host; however, the mechanisms by which TEs counteract silencing are poorly understood. Here, we show that a class of TEs in rice produces a microRNA (miRNA to suppress host silencing. Members of the microRNA820 (miR820 gene family are located within CACTA DNA transposons in rice and target a de novo DNA methyltransferase gene, OsDRM2, one of the components of epigenetic silencing. We confirmed that miR820 negatively regulates the expression of OsDRM2. In addition, we found that expression levels of various TEs are increased quite sensitively in response to decreased OsDRM2 expression and DNA methylation at TE loci. Furthermore, we found that the nucleotide sequence of miR820 and its recognition site within the target gene in some Oryza species have co-evolved to maintain their base-pairing ability. The co-evolution of these sequences provides evidence for the functionality of this regulation. Our results demonstrate how parasitic elements in the genome escape the host's defense machinery. Furthermore, our analysis of the regulation of OsDRM2 by miR820 sheds light on the action of transposon-derived small RNAs, not only as a defense mechanism for host genomes but also as a regulator of interactions between hosts and their parasitic elements.

Serum cytokine levels in patients with hepatocellular carcinoma.

Science.gov (United States)

Capone, Francesca; Costantini, Susan; Guerriero, Eliana; Calemma, Rosa; Napolitano, Maria; Scala, Stefania; Izzo, Francesco; Castello, Giuseppe

2010-06-01

The role played by the microenvironment in cancer induction, promotion and progression is crucial. Emerging evidence suggests that cytokines, chemokines and growth factors are major players in carcinogenesis. Therefore, a detailed understanding of factors and mechanisms associated with the processes leading from inflammation to cancer could improve the therapeutic strategies against this disease. We have used hepatocarcinoma as our model in this study. We evaluated the serum levels of 50 different cytokines, chemokines and growth factors in patients affected by HCC with chronic HCV-related hepatitis and liver cirrhosis using multiplex biometric ELISA-based immunoassay. Our data showed that some pro-inflammatory molecules were significantly up-regulated in these patients, and highlighted the complexity of the cytokine network in this disease. This work suggests the need to monitor these proteins in order to define a profile that could characterize patients with HCC or to help identify useful markers. This could lead to better definition of the disease state, and to an increased understanding of the relationships between chronic inflammation and cancer.

Factores de virulencia del patógeno intestinal Entamoeba histolytica Virulence factors of the enteric protozoan parasite Entamoeba histolytica

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Juanita Trejos-Suárez

2009-06-01

Full Text Available Entamoeba histolytica es un protozoo entérico causante de la amebiasis intestinal y extraintestinal. Se calcula que 10% de la población mundial está infectada por el complejo Entamoeba histolytica/Entamoeba dispar. Según la OMS, hay 500 millones de nuevas infecciones por año y, aproximadamente, 70.000 a 100.000 muertes a causas de ellas. Este parásito cumple un proceso de invasión muy elaborado, en el cual se secretan y expresan proteínas que le permiten adherirse al epitelio, degradar la matriz extracelular y producir citólisis de las células epiteliales para penetrar dentro de la mucosa. El entendimiento de estos factores de virulencia ha generado múltiples estudios en diferentes áreas de las ciencias biomédicas, desde métodos diagnósticos cada vez más sensibles y específicos hasta candidatos para vacunas, lo que abre nuevas expectativas terapéuticas a raíz de estos estudios.The enteric protozoan parasite Entamoeba histolytica is a human pathogen that causes widespread morbidity and mortality. It is estimated that 10% of the world’s population is infected with the complex Entamoeba histolytica/ Entamoeba dispar. According to the WHO there are 500 million new infections per year and it is the cause of approximately 70,000 - 100,000 deaths. This parasite has a very elaborate process of invasion, where there are expressed and secreted proteins that allow the parasite to adhere to the epithelium, to degrade extracellular matrix and to penetrate epithelial cells within the mucosa. Numerous studies have been carried out to understand how virulence factors work in diverse areas of biomedical sciences. The studies have proposed diagnostic tests to increase the sensitivity and specificity and to find vaccine candidates, which are an opening way to new therapeutic expectations.

Exosome Secretion by the Parasitic Protozoan Leishmania within the Sand Fly Midgut

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Vanessa Diniz Atayde

2015-11-01

Full Text Available Despite several studies describing the secretion of exosomes by Leishmania in vitro, observation of their formation and release in vivo has remained a major challenge. Herein, we show that Leishmania constitutively secretes exosomes within the lumen of the sand fly midgut through a mechanism homologous to the mammalian pathway. Through egestion experiments, we demonstrate that Leishmania exosomes are part of the sand fly inoculum and are co-egested with the parasite during the insect’s bite, possibly influencing the host infectious process. Indeed, co-inoculation of mice footpads with L. major plus midgut-isolated or in-vitro-isolated L. major exosomes resulted in a significant increase in footpad swelling. Notably, co-injections produced exacerbated lesions through overinduction of inflammatory cytokines, in particular IL-17a. Our data indicate that Leishmania exosomes are an integral part of the parasite’s infectious life cycle, and we propose to add these vesicles to the repertoire of virulence factors associated with vector-transmitted infections.

Cytokine production by oral and peripheral blood neutrophils in adult periodontitis.

Science.gov (United States)

Galbraith, G M; Hagan, C; Steed, R B; Sanders, J J; Javed, T

1997-09-01

Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) also possess bone-resorptive properties, and are generally considered to play a role in the pathogenesis of periodontal disease. In the present study, TNF-alpha and IL-1 beta production by oral and peripheral blood polymorphonuclear leukocytes (PMN) was examined in 40 patients with adult periodontitis and 40 orally healthy matched controls. Oral PMN released considerable amounts of both cytokines in unstimulated culture, and there was no difference between patients and controls when the cytokine levels were corrected for cell number. However, when the effect of disease activity was examined, cytokine release by oral PMN was found to be greatest in patients with advanced periodontitis. Within the healthy control group, IL-1 beta production by oral PMN was significantly higher in males (Mann-Whitney test, P = 0.0008). Examination of IL-1 beta production by peripheral blood PMN exposed to recombinant human granulocyte-macrophage colony stimulating factor revealed no difference between the patient and control groups. In contrast, IL-1 beta production by peripheral blood PMN was significantly reduced in patients with advanced disease (Mann-Whitney test, P = 0.02), and peripheral PMN IL-1 beta synthesis was greater in female controls (Mann-Whitney test, P = 0.054). No effect of race on cytokine production could be discerned in patients or controls. These results indicate that several factors influence cytokine production in oral health and disease, and that a dichotomy in cytokine gene expression exists between oral and peripheral blood PMN in adult periodontitis.

Prevalence of intestinal parasites and associated risk factors among HIV/AIDS patients with pre-ART and on-ART attending dessie hospital ART clinic, Northeast Ethiopia.

Science.gov (United States)

Missaye, Assefa; Dagnew, Mulat; Alemu, Abebe; Alemu, Agersew

2013-02-25

Intestinal parasites are a major concern in most developing countries where HIV/AIDS case are concentrate and almost 80% of AIDS patients die of AIDS-related infections. In the absence of ART, HIV/AIDS patients in developing countries unfortunately continue to suffer from the consequences of opportunistic parasites. But this prevalence has dramatically decreased in countries where antiretroviral agents are widely available. Therefore, the aim of this study was to assess the prevalence of intestinal parasite and risk factor among pre- ART and on ART adult HIV/ AIDS patients attending ART clinic in Dessie hospital. A comparative cross-sectional study was conducted among pre-ART and on ART adult HIV/AIDS patients of Dessie Hospital. A total of 272 (136 from each group) study subjects were selected by using systematic random sampling. Stool sample was collected and processed using direct wet mount, formol-ether concentration technique and modified Ziehl-Neelson staining techniques. A structured questionnaire was used to collect data on Sociodemographic & associated risk factors. Data was entered and analyzed by using SPSS 16 software and logistic regressions were applied to assess any association between explanatory factors and outcome variables. The overall prevalence of IP in pre-ART and on-ART was 39% and 17.6%, respectively with significant decrease of intestinal parasite in the ART era (p intestinal parasite. The overall prevalence of IP was differ by ART status and opportunistic parasite like cryptosporidium spps were found in low CD4 counts in ART naive patients. This study identified some environmental and some clinical finding as determinant factor for IP infections. Therefore, public health measures and adherence to ART should be strengthened to improve the quality of life of these patients.

Babesia spp. in European wild ruminant species: parasite diversity and risk factors for infection

OpenAIRE

Michel , Adam O; Mathis , Alexander; Ryser-Degiorgis , Marie-Pierre

2014-01-01

International audience; Babesia are tick-borne parasites that are increasingly considered as a threat to animal and public health. We aimed to assess the role of European free-ranging wild ruminants as maintenance mammalian hosts for Babesia species and to determine risk factors for infection. EDTA blood was collected from 222 roe deer (Capreolus c. capreolus), 231 red deer (Cervus e. elaphus), 267 Alpine chamois (Rupicapra r. rupicapra) and 264 Alpine ibex (Capra i. ibex) from all over Switz...

Chronic ethanol consumption modulates growth factor release, mucosal cytokine production, and microRNA expression in nonhuman primates.

Science.gov (United States)

Asquith, Mark; Pasala, Sumana; Engelmann, Flora; Haberthur, Kristen; Meyer, Christine; Park, Byung; Grant, Kathleen A; Messaoudi, Ilhem

2014-04-01

Chronic alcohol consumption has been associated with enhanced susceptibility to both systemic and mucosal infections. However, the exact mechanisms underlying this enhanced susceptibility remain incompletely understood. Using a nonhuman primate model of ethanol (EtOH) self-administration, we examined the impact of chronic alcohol exposure on immune homeostasis, cytokine, and growth factor production in peripheral blood, lung, and intestinal mucosa following 12 months of chronic EtOH exposure. EtOH exposure inhibited activation-induced production of growth factors hepatocyte growth factor (HGF), granulocyte colony-stimulating factor (G-CSF), and vascular-endothelial growth factor (VEGF) by peripheral blood mononuclear cells (PBMC). Moreover, EtOH significantly reduced the frequency of colonic Th1 and Th17 cells in a dose-dependent manner. In contrast, we did not observe differences in lymphocyte frequency or soluble factor production in the lung of EtOH-consuming animals. To uncover mechanisms underlying reduced growth factor and Th1/Th17 cytokine production, we compared expression levels of microRNAs in PBMC and intestinal mucosa. Our analysis revealed EtOH-dependent up-regulation of distinct microRNAs in affected tissues (miR-181a and miR-221 in PBMC; miR-155 in colon). Moreover, we were able to detect reduced expression of the transcription factors STAT3 and ARNT, which regulate expression of VEGF, G-CSF, and HGF and contain targets for these microRNAs. To confirm and extend these observations, PBMC were transfected with either mimics or antagomirs of miR-181 and miR-221, and protein levels of the transcription factors and growth factors were determined. Transfection of microRNA mimics led to a reduction in both STAT3/ARNT as well as VEGF/HGF/G-CSF levels. The opposite outcome was observed when microRNA antagomirs were transfected. Chronic EtOH consumption significantly disrupts both peripheral and mucosal immune homeostasis, and this dysregulation may be

Intradermal Immunization of Leishmania donovani Centrin Knock-Out Parasites in Combination with Salivary Protein LJM19 from Sand Fly Vector Induces a Durable Protective Immune Response in Hamsters.

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Jacqueline Araújo Fiuza

2016-01-01

Full Text Available Visceral leishmaniasis (VL is a neglected tropical disease and is fatal if untreated. There is no vaccine available against leishmaniasis. The majority of patients with cutaneous leishmaniasis (CL or VL develop a long-term protective immunity after cure from infection, which indicates that development of an effective vaccine against leishmaniasis is possible. Such protection may also be achieved by immunization with live attenuated parasites that do not cause disease. We have previously reported a protective response in mice, hamsters and dogs with Leishmania donovani centrin gene knock-out parasites (LdCen-/-, a live attenuated parasite with a cell division specific centrin1 gene deletion. In this study we have explored the effects of salivary protein LJM19 as an adjuvant and intradermal (ID route of immunization on the efficacy of LdCen-/- parasites as a vaccine against virulent L. donovani.To explore the potential of a combination of LdCen-/- parasites and salivary protein LJM19 as vaccine antigens, LdCen-/- ID immunization followed by ID challenge with virulent L. donovani were performed in hamsters in a 9-month follow up study. We determined parasite burden (serial dilution, antibody production (ELISA and cytokine expression (qPCR in these animals. Compared to controls, animals immunized with LdCen-/- + LJM19 induced a strong antibody response, a reduction in spleen and liver parasite burden and a higher expression of pro-inflammatory cytokines after immunization and one month post-challenge. Additionally, a low parasite load in lymph nodes, spleen and liver, and a non-inflamed spleen was observed in immunized animals 9 months after the challenge infection.Our results demonstrate that an ID vaccination using LdCen-/-parasites in combination with sand fly salivary protein LJM19 has the capability to confer long lasting protection against visceral leishmaniasis that is comparable to intravenous or intracardial immunization.

Plant-parasitic nematodes: towards understanding molecular players in stress responses.

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Gillet, François-Xavier; Bournaud, Caroline; Antonino de Souza Júnior, Jose Dijair; Grossi-de-Sa, Maria Fatima

2017-03-01

Plant-parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant-nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence. Nematodes trigger crucial regulatory cytoprotective mechanisms, including antioxidant and detoxification pathways. Knowledge of the upstream regulatory components that contribute to both of these pathways in PPNs remains elusive. In this review, we discuss how PPNs probably orchestrate cytoprotection to resist plant immune responses, postulating that it may be derived from ancient molecular mechanisms. The review focuses on two transcription factors, DAF-16 and SKN-1 , which are conserved in the animal kingdom and are central regulators of cell homeostasis and immune function. Both regulate the unfolding protein response and the antioxidant and detoxification pathways. DAF-16 and SKN-1 target a broad spectrum of Caenorhabditis elegans genes coding for numerous protein families present in the secretome of PPNs. Moreover, some regulatory elements of DAF-16 and SKN-1 from C. elegans have already been identified as important genes for PPN infection. DAF-16 and SKN-1 genes may play a pivotal role in PPNs during parasitism. In the context of their hub status and mode of regulation, we suggest alternative strategies for control of PPNs through RNAi approaches. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company.

Targeting channels and transporters in protozoan parasite infections

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Meier, Anna; Erler, Holger; Beitz, Eric

2018-03-01

Infectious diseases caused by pathogenic protozoa are among the most significant causes of death in humans. Therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains. Many of the current anti-parasite drugs target soluble enzymes, generate unspecific oxidative stress, or act by an unresolved mechanism within the parasite. In recent years, collections of drug-like compounds derived from large-scale phenotypic screenings, such as the malaria or pathogen box, have been made available to researchers free of charge boosting the identification of novel promising targets. Remarkably, several of the compound hits have been found to inhibit membrane proteins at the periphery of the parasites, i.e. channels and transporters for ions and metabolites. In this review, we will focus on the progress made on targeting channels and transporters at different levels and the potential for use against infections with apicomplexan parasites mainly Plasmodium spp. (malaria) and Toxoplasma gondii (toxoplasmosis), with kinetoplastids Trypanosoma brucei (sleeping sickness), Trypanosoma cruzi (Chagas disease) and Leishmania ssp. (leishmaniasis), and the amoeba Entamoeba histolytica (amoebiasis).

Cytokines: abnormalities in major depression and implications for pharmacological treatment.

LENUS (Irish Health Repository)

O'Brien, Sinead M

2012-02-03

The role of cytokines in depression was first considered when the cytokine interferon resulted in "sickness behaviour", the symptoms of which are similar to those of major depression. The latter is associated with an increase in pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). These cytokines are potent modulators of corticotropin-releasing hormone (CRH) which produces heightened hypothalamic-pituitary-adrenal axis (HPA) activity characterized by increases in ACTH and cortisol, both of which are reported elevated in major depression. Antidepressant treatment has immunomodulatory effects with increases in the production of IL-10, which is an anti-inflammatory cytokine. This review based on a Medline search from 1980-2003, focuses on the evidence available of cytokine changes in acute stress, chronic stress and major depression. It examines the effects of antidepressant treatment on immune parameters in both animal models and clinical trials. We suggest that future antidepressants may target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.

Cytokines and Organ Failure in Acute Pancreatitis

DEFF Research Database (Denmark)

Malmstrøm, Marie Louise; Hansen, Mark Berner; Andersen, Anders Møller

2012-01-01

Objectives: We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP). Methods: Interleukin (IL) 6, IL-8, IL-18, and tumor necrosis factor > were measured on admission...

Morphological variation in the cosmopolitan fish parasite Neobenedenia girellae (Capsalidae: Monogenea).

Science.gov (United States)

Brazenor, Alexander K; Saunders, Richard J; Miller, Terrence L; Hutson, Kate S

2018-02-01

Intra-species morphological variation presents a considerable problem for species identification and can result in taxonomic confusion. This is particularly pertinent for species of Neobenedenia which are harmful agents in captive fish populations and have historically been identified almost entirely based on morphological characters. This study aimed to understand how the morphology of Neobenedenia girellae varies with host fish species and the environment. Standard morphological features of genetically indistinct parasites from various host fish species were measured under controlled temperatures and salinities. An initial field-based investigation found that parasite morphology significantly differed between genetically indistinct parasites infecting various host fish species. The majority of the morphological variation observed (60%) was attributed to features that assist in parasite attachment to the host (i.e. the posterior and anterior attachment organs and their accessory hooks) which are important characters in monogenean taxonomy. We then experimentally examined the effects of the interaction between host fish species and environmental factors (temperature and salinity) on the morphology of isogenic parasites derived from a single, isolated hermaphroditic N. girellae infecting barramundi, Lates calcarifer. Experimental infection of L. calcarifer and cobia, Rachycentron canadum, under controlled laboratory conditions did not confer host-mediated phenotypic plasticity in N. girellae, suggesting that measured morphological differences could be adaptive and only occur over multiple parasite generations. Subsequent experimental infection of a single host species, L. calcarifer, at various temperatures (22, 30 and 32 °C) and salinities (35 and 40‰) showed that in the cooler environments (22 °C) N. girellae body proportions were significantly smaller compared with warmer temperatures (30 and 32 °C; P < 0.0001), whereas salinity had no effect. This

TGF-β mimic proteins form an extended gene family in the murine parasite Heligmosomoides polygyrus.

Science.gov (United States)

Smyth, Danielle J; Harcus, Yvonne; White, Madeleine P J; Gregory, William F; Nahler, Janina; Stephens, Ian; Toke-Bjolgerud, Edward; Hewitson, James P; Ivens, Alasdair; McSorley, Henry J; Maizels, Rick M

2018-04-01

We recently reported the discovery of a new parasite-derived protein that functionally mimics the immunosuppressive cytokine transforming growth factor (TGF)-β. The Heligmosomoides polygyrus TGF-β Mimic (Hp-TGM) shares no homology to any TGF-β family member, however it binds the mammalian TGF-β receptor and induces expression of Foxp3, the canonical transcription factor of both mouse and human regulatory T cells. Hp-TGM consists of five atypical Complement Control Protein (CCP, Pfam 00084) domains, each lacking certain conserved residues and 12-15 amino acids longer than the 60-70 amino acids consensus domain, but with a recognizable 3-cysteine, tryptophan, cysteine motif. We now report on the identification of a family of nine related Hp-TGM homologues represented in the secreted proteome and transcriptome of H. polygyrus. Recombinant proteins from five of the nine new TGM members were tested for TGF-β activity, but only two were functionally active in an MFB-F11 reporter assay, and by the induction of T cell Foxp3 expression. Sequence comparisons reveal that proteins with functional activity are similar or identical to Hp-TGM across the first three CCP domains, but more variable in domains 4 and 5. Inactive proteins diverged in all domains, or lacked some domains entirely. Testing truncated versions of Hp-TGM confirmed that domains 1-3 are essential for full activity in vitro, while domains 4 and 5 are not required. Further studies will elucidate whether these latter domains fulfill other functions in promoting host immune regulation during infection and if the more divergent family members play other roles in immunomodulation. Copyright © 2018. Published by Elsevier Ltd.

Gastrointestinal function in the parasitized host

International Nuclear Information System (INIS)

Castro, G.A.

1981-01-01

Emphasis in this review is on (1) digestive-absorptive, secretory and smooth muscle functions altered by gastrointestinal (GI) parasites, (2) mechanisms by which parasites induce changes, and (3) the influence of parasite-induced alterations on the health of the host. Examples involving laboratory and domestic animals indicate that inflammation is an important factor in pathological alterations in epithelial and smooth muscle tissues throughout the alimentary canal. Observations on GI secretory activity reveal an influence of parasites on the host GI endocrine system. It is argued that assessments of the significance of parasite-induced changes on the host must be balanced with the adaptive potential and 'reserve capacity' of the GI system. In this regard host immunity should be considered a specific adaptation. Some tracer studies are mentioned marginally, such as the use of 14 C polyethylene glycol to estimate the direction of not fluid movement in the small intestine, and the use of 51 Cr to demonstrate the significantly faster intestinal transit in Trichinella spiralis infected animals

Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles.

Science.gov (United States)

Guimarães, Poliana Macedo; Scavuzzi, Bruna Miglioranza; Stadtlober, Nicole Perugini; Franchi Santos, Lorena Flor da Rosa; Lozovoy, Marcell Alysson Batisti; Iriyoda, Tatiana Mayumi Veiga; Costa, Neide Tomimura; Reiche, Edna Maria Vissoci; Maes, Michael; Dichi, Isaias; Simão, Andréa Name Colado

2017-10-01

The aims of this study were to delineate cytokine profiles of systemic lupus erythematosus (SLE), construct prediction models for diagnosis and disease activity using those profiles, and to examine the associations between TNFB Ncol polymorphism, body mass index (BMI) and vitamin D levels with cytokine levels. Two hundred SLE patients and 196 healthy controls participated in this case-control study. Plasma cytokines levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL- 4, IL-6, IL-10, IL-12 and IL-17 were measured and cytokines profiles were computed. IL-6, IL-12, IL-17, IFN-γ and IL-10 levels were significantly higher in SLE, while IL-4 was lower in SLE. The Th1/Th2 and Th1+Th17/Th2 profiles were significantly higher in SLE than in healthy controls, whereas there were no significant differences in the proinflammatory cytokine profile (TNFα+IL-6+IL-1β). In total, 90.4% of all subjects were correctly classified using Th1+Th17 profile and IL-10 (positively associated) and IL-4 (negatively associated) as predictor variables (sensitivity=66.7% and specificity=96.9%). In all, 20.9% of the variance in the SLE Disease Activity Index was predicted by the Th1+Th17/Th2 ratio, IL-10 and BMI (all positively) and proinflammatory profile (inversely associated). B1/B1 genotype is accompanied by increased IL-17 and Th17/Th2 ratio, while B1/B2 genotype is accompanied by higher IL-4 and IFNγ values. 25-OH vitamin D was inversely associated with IFN-γ levels. SLE is accompanied by Th1, Th17 and Treg profile and lowered IL-4 production. Lowered vitamin D levels and B1/B1 genotype, but not BMI, contribute to changes in cytokines profiles. Future treatments should target Th1, Th2 and Th17 profiles rather than inflammatory cytokines.

Intestinal parasitic infections and associated risk factors in preschoolers from different urban settings in Central-Western Brazil

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João Gabriel Guimarães Luz

2017-07-01

Full Text Available Objective: To investigate the prevalence of intestinal parasitic infections and the associated risk factors in children attending preschools located in areas with different socioeconomic and structural features in the city of Rondonópolis, State of Mato Grosso, Brazil. Methods: A cross-sectional survey was conducted between 2015 and 2016 among four-to-five years old children. Initially, urban neighborhoods with preschools were classified into five risk strata for parasitic infections, which were defined on the basis of socioeconomic and structural variables. Then, one school from each stratum was randomly chosen for data collection. After obtaining the written informed consent from parents or guardians, the children provided stool samples for examination. Interviews were conducted with parents or guardians to determine the associated risk factors. Results: Coproparasitological tests were performed on 215 (46.5% preschoolers, and the overall prevalence was 22.8%. The occurrence of such infections increased with the increase in risk stratum of the neighborhood. Protozoa infections, mainly by Entamoeba coli (11.2% and Giardia duodenalis (9.8%, were the most frequent. The consumption of tap water (OR = 3.56, P = 0.002, no washing of fruits and vegetables before consumption (OR = 3.44, P = 0.002, and no hand washing before eating (OR = 2.63, P = 0.004 were associated with these infections. Conclusions: The prevalence of intestinal parasites among Rondonópolis preschoolers is relevant and associated with precarious hygienic–sanitary behavior, especially in areas with poor socioeconomic and structural conditions.

Cytokine, antibody and proliferative cellular responses elicited by Taenia solium calreticulin upon experimental infection in hamsters.

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Fela Mendlovic

Full Text Available Taenia solium causes two diseases in humans, cysticercosis and taeniosis. Tapeworm carriers are the main risk factor for neurocysticercosis. Limited information is available about the immune response elicited by the adult parasite, particularly the induction of Th2 responses, frequently associated to helminth infections. Calreticulin is a ubiquitous, multifunctional protein involved in cellular calcium homeostasis, which has been suggested to play a role in the regulation of immune responses. In this work, we assessed the effect of recombinant T. solium calreticulin (rTsCRT on the cytokine, humoral and cellular responses upon experimental infection in Syrian Golden hamsters (Mesocricetus auratus. Animals were infected with T. solium cysticerci and euthanized at different times after infection. Specific serum antibodies, proliferative responses in mesenteric lymph nodes and spleen cells, as well as cytokines messenger RNA (mRNA were analyzed. The results showed that one third of the infected animals elicited anti-rTsCRT IgG antibodies. Interestingly, mesenteric lymph node (MLN cells from either infected or non-infected animals did not proliferate upon in vitro stimulation with rTsCRT. Additionally, stimulation with a tapeworm crude extract resulted in increased expression of IL-4 and IL-5 mRNA. Upon stimulation, rTsCRT increased the expression levels of IL-10 in spleen and MLN cells from uninfected and infected hamsters. The results showed that rTsCRT favors a Th2-biased immune response characterized by the induction of IL-10 in mucosal and systemic lymphoid organs. Here we provide the first data on the cytokine, antibody and cellular responses to rTsCRT upon in vitro stimulation during taeniasis.

Inhibitory effects of methamphetamine on mast cell activation and cytokine/chemokine production stimulated by lipopolysaccharide in C57BL/6J mice.

Science.gov (United States)

Xue, Li; Geng, Yan; Li, Ming; Jin, Yao-Feng; Ren, Hui-Xun; Li, Xia; Wu, Feng; Wang, Biao; Cheng, Wei-Ying; Chen, Teng; Chen, Yan-Jiong

2018-04-01

Previous studies have demonstrated that methamphetamine (MA) influences host immunity; however, the effect of MA on lipopolysaccharide (LPS)-induced immune responses remains unknown. Mast cells (MCs) are considered to serve an important role in the innate and acquired immune response, but it remains unknown whether MA modulates MC activation and LPS-stimulated cytokine production. The present study aimed to investigate the effect of MA on LPS-induced MC activation and the production of MC-derived cytokines in mice. Markers for MC activation, including cluster of differentiation 117 and the type I high affinity immunoglobulin E receptor, were assessed in mouse intestines. Levels of MC-derived cytokines in the lungs and thymus were also examined. The results demonstrated that cytokines were produced in the bone marrow-derived mast cells (BMMCs) of mice. The present study demonstrated that MA suppressed the LPS-mediated MC activation in mouse intestines. MA also altered the release of MC cytokines in the lung and thymus following LPS stimulation. In addition, LPS-stimulated cytokines were decreased in the BMMCs of mice following treatment with MA. The present study demonstrated that MA may regulate LPS-stimulated MC activation and cytokine production.

Prevalence of intestinal parasitic infections and associated risk factors among schoolchildren in the Plateau Central and Centre-Ouest regions of Burkina Faso.

Science.gov (United States)

Erismann, Séverine; Diagbouga, Serge; Odermatt, Peter; Knoblauch, Astrid M; Gerold, Jana; Shrestha, Akina; Grissoum, Tarnagda; Kaboré, Aminata; Schindler, Christian; Utzinger, Jürg; Cissé, Guéladio

2016-10-18

Unsafe drinking water, unimproved sanitation and lack of hygiene pose health risks, particularly to children in low- and middle-income countries. This study aimed to assess the prevalence and risk factors of intestinal parasitic infections in school-aged children in two regions of Burkina Faso. A cross-sectional survey was carried out in February 2015 with 385 children aged 8-14 years from eight randomly selected schools in the Plateau Central and Centre-Ouest regions of Burkina Faso. Stool samples were subjected to the Kato-Katz and a formalin-ether concentration method for the diagnosis of helminths and intestinal protozoa infections. Urine samples were examined with a urine filtration technique for Schistosoma haematobium eggs. Water samples from community sources (n = 37), children's households (n = 95) and children's drinking water cups (n = 113) were analysed for contamination with coliform bacteria and faecal streptococci. Data on individual and family-level risk factors were obtained using a questionnaire. Mixed logistic regression models were employed to determine factors associated with intestinal parasitic infections in schoolchildren. Intestinal parasitic infections were highly prevalent; 84.7 % of the children harboured intestinal protozoa, while helminth infections were diagnosed in 10.7 % of the children. We found significantly lower odds of pathogenic intestinal protozoa infection (Entamoeba histolytica/E. dispar and Giardia intestinalis) among children from the Plateau Central, compared to the Centre-Ouest region (P parasitic infections in children. Intestinal protozoa but not helminths were highly prevalent among schoolchildren in randomly selected schools in two regions of Burkina Faso. Our findings call for specific public health measures tailored to school-aged children and rural communities in this part of Burkina Faso. It will be interesting to assess the effect of water, sanitation and hygiene interventions on the

Interactions between microbial agents and gypsy moth parasites

Science.gov (United States)

Ronald M. Weseloh

1985-01-01

The parasite Cotesia melanoscelus attacks small gypsy moth larvae more successfully than large ones, and Bacillus thuringiensis retards the growth of caterpillars it does not kill. Together, both factors lead to higher parasitism by C. melanoscelus in areas sprayed with B. thuringiensis than...

Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis.

Science.gov (United States)

Partridge, Emily A; Le Roy, Christine; Di Guglielmo, Gianni M; Pawling, Judy; Cheung, Pam; Granovsky, Maria; Nabi, Ivan R; Wrana, Jeffrey L; Dennis, James W

2004-10-01

The Golgi enzyme beta1,6 N-acetylglucosaminyltransferase V (Mgat5) is up-regulated in carcinomas and promotes the substitution of N-glycan with poly N-acetyllactosamine, the preferred ligand for galectin-3 (Gal-3). Here, we report that expression of Mgat5 sensitized mouse cells to multiple cytokines. Gal-3 cross-linked Mgat5-modified N-glycans on epidermal growth factor and transforming growth factor-beta receptors at the cell surface and delayed their removal by constitutive endocytosis. Mgat5 expression in mammary carcinoma was rate limiting for cytokine signaling and consequently for epithelial-mesenchymal transition, cell motility, and tumor metastasis. Mgat5 also promoted cytokine-mediated leukocyte signaling, phagocytosis, and extravasation in vivo. Thus, conditional regulation of N-glycan processing drives synchronous modification of cytokine receptors, which balances their surface retention against loss via endocytosis.

Role of Nuclear Factor (Erythroid-Derived 2-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells

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Anna Hammer

2017-12-01

Full Text Available To date, the intracellular signaling pathways involved in dendritic cell (DC function are poorly understood. The antioxidative transcription factor nuclear factor (erythroid-derived 2-like 2 (Nrf2 has been shown to affect maturation, function, and subsequent DC-mediated T cell responses of murine and human DCs. In experimental autoimmune encephalomyelitis (EAE, as prototype animal model for a T helper cell-mediated autoimmune disease, antigen presentation, cytokine production, and costimulation by DCs play a major role. We explore the role of Nrf2 in DC function, and DC-mediated T cell responses during T cell-mediated autoimmunity of the central nervous system using genetic ablation and pharmacological activation in mice and men to corroborate our data in a translational setting. In murine and human DCs, monomethyl fumarate induced Nrf2 signaling inhibits DC maturation and DC-mediated T cell proliferation by reducing inflammatory cytokine production and expression of costimulatory molecules. In contrast, Nrf2-deficient DCs generate more activated T helper cells (Th1/Th17 but fewer regulatory T cells and foster T cell proliferation. Transfer of DCs with Nrf2 activation during active EAE reduces disease severity and T cell infiltration. Our data demonstrate that Nrf2 signaling modulates autoimmunity in murine and human systems via inhibiting DC maturation and function thus shedding further light on the mechanism of action of antioxidative stress pathways in antigen-presenting cells.

Trans-generational parasite protection associated with paternal diet.

Science.gov (United States)

Sternberg, Eleanore D; de Roode, Jacobus C; Hunter, Mark D

2015-01-01

Multiple generations of hosts are often exposed to the same pathogens, favouring the evolution of trans-generational defences. Because females have more opportunities to transfer protective molecules to offspring, many studies have focused on maternally derived protection. However, males of many species can transfer compounds along with sperm, including chemicals that could provide protection. Here, we assess maternally and paternally derived protection in a monarch butterfly-protozoan parasite system where parasite resistance is heavily influenced by secondary plant chemicals, known as cardenolides, present in the larval diet of milkweed plants. We reared monarch butterflies on medicinal and non-medicinal milkweed species and then measured resistance of their offspring to infection. We also measured cardenolide content in adult monarchs reared on the two species, and in the eggs that they produced. We found that offspring were more resistant to infection when their fathers were reared on medicinal milkweed, while maternal diet had less of an effect. We also found that eggs contained the highest levels of cardenolides when both parents were reared on the medicinal species. Moreover, females reared on non-medicinal milkweed produced eggs with significantly higher levels of cardenolides if they mated with males reared on the medicinal milkweed species. However, we found an equivocal relationship between the cardenolides present in eggs and parasite resistance in the offspring. Our results demonstrate that males reared on medicinal plants can transfer protection to their offspring, but the exact mechanism remains unresolved. This suggests that paternal protection from parasitism might be important, particularly when there are environmental sources of parasite resistance and when males transfer spermatophores during mating. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

Analysis of cytokine profile and growth factors in platelet-rich plasma obtained by open systems and commercial columns.

Science.gov (United States)

Pochini, Alberto de Castro; Antonioli, Eliane; Bucci, Daniella Zanetti; Sardinha, Luiz Roberto; Andreoli, Carlos Vicente; Ferretti, Mario; Ejnisman, Benno; Goldberg, Anna Carla; Cohen, Moisés

2016-01-01

To evaluate growth factors and cytokines in samples of platelet-rich plasma obtained by three different centrifugation methods. Peripheral blood of six individuals with no hematological diseases, aged 18 to 68 years, was drawn to obtain platelet-rich plasma, using the open method and commercial columns by Medtronic and Biomet. The products obtained with the different types of centrifugation were submitted to laboratory analysis, including pro-inflammatory cytokines and chemokines by flow cytometry assays, the concentration of fibroblast growth factors-2 (FGF-2) and transforming growth factor-beta1 (TGF-β1). The diverse separation methods generated systematically different profiles regarding number of platelets and leukocytes. The Medtronic system yielded a product with the highest concentration of platelets, and the open method, with the lowest concentration of platelets. The results of cytokine analysis showed that the different types of centrifugation yielded products with high concentrations of interleukin 8, interleukin 1β. The open system resulted in a product with high levels of interleukin 6. Other cytokines and chemokines measured were similar between systems. The product obtained with the open method showed higher levels of TGF-β1 in relation to other systems and low FGF-2 levels. The formed elements, growth factors and cytokines in samples of platelet-rich plasma varied according to the centrifugation technique used. Avaliar fatores de crescimento e citocinas em amostras de plasma rico em plaquetas obtidas por três diferentes métodos de centrifugação. Foi coletado sangue periférico de seis indivíduos, sem doença hematológica, com idades entre 18 e 68 anos, para obtenção de plasma rico em plaquetas, utilizando o método aberto e sistemas comerciais das empresas Medtronic e Biomet. Os produtos obtidos com os diferentes tipos de centrifugação foram submetidos às análises laboratoriais, incluindo citocinas próinflamatórias e quimiocinas

True versus false parasite interactions: a robust method to take risk factors into account and its application to feline viruses.

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Eléonore Hellard

Full Text Available Multiple infections are common in natural host populations and interspecific parasite interactions are therefore likely within a host individual. As they may seriously impact the circulation of certain parasites and the emergence and management of infectious diseases, their study is essential. In the field, detecting parasite interactions is rendered difficult by the fact that a large number of co-infected individuals may also be observed when two parasites share common risk factors. To correct for these "false interactions", methods accounting for parasite risk factors must be used.In the present paper we propose such a method for presence-absence data (i.e., serology. Our method enables the calculation of the expected frequencies of single and double infected individuals under the independence hypothesis, before comparing them to the observed ones using the chi-square statistic. The method is termed "the corrected chi-square." Its robustness was compared to a pre-existing method based on logistic regression and the corrected chi-square proved to be much more robust for small sample sizes. Since the logistic regression approach is easier to implement, we propose as a rule of thumb to use the latter when the ratio between the sample size and the number of parameters is above ten. Applied to serological data for four viruses infecting cats, the approach revealed pairwise interactions between the Feline Herpesvirus, Parvovirus and Calicivirus, whereas the infection by FIV, the feline equivalent of HIV, did not modify the risk of infection by any of these viruses.This work therefore points out possible interactions that can be further investigated in experimental conditions and, by providing a user-friendly R program and a tutorial example, offers new opportunities for animal and human epidemiologists to detect interactions of interest in the field, a crucial step in the challenge of multiple infections.

Proliferative Vitreoretinopathy after Eye Injuries: An Overexpression of Growth Factors and Cytokines Leading to a Retinal Keloid

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Francesco Morescalchi

2013-01-01

Full Text Available Eye injury is a significant disabling worldwide health problem. Proliferative Vitreoretinopathy (PVR is a common complication that develops in up to 40–60% of patients with an open-globe injury. Our knowledge about the pathogenesis of PVR has improved in the last decades. It seems that the introduction of immune cells into the vitreous, like in penetrating ocular trauma, triggers the production of growth factors and cytokines that come in contact with intra-retinal cells, like Müller cells and RPE cells. Growth factors and cytokines drive the cellular responses leading to PVR’s development. Knowledge of the pathobiological and pathophysiological mechanisms involved in posttraumatic PVR is increasing the possibilities of management, and it is hoped that in the future our treatment strategies will evolve, in particular adopting a multidrug approach, and become even more effective in vision recovery. This paper reviews the current literature and clinical trial data on the pathogenesis of PVR and its correlation with ocular trauma and describes the biochemical/molecular events that will be fundamental for the development of novel treatment strategies. This literature review included PubMed articles published from 1979 through 2013. Only studies written in English were included.

Intestinal parasites among Yanomâmi indians

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Confalonieri, U. E.; Araújo, A. J.; Ferreira, L. F.

1989-01-01

The findings of intestinal helminths and protozoans parasites from the Yanomâmi indians of the Roraima State in Brazil are reported. The fecal samples were collected before these communities started a permanent contact with non-indians. Comments are made on the possible ecological and evolutionary factors responsible for the patterns of parasitism observed.

The Role of Cytokines in the Pathophysiology of Suicidal Behavior

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Ganança, Licínia; Oquendo, Maria A.; Tyrka, Audrey R.; Cisneros-Trujillo, Sebastian; Mann, J. John; Sublette, M. Elizabeth

2016-01-01

Objective Immune dysregulation has been implicated in depression and other psychiatric disorders. What is less clear is how immune dysregulation can affect risk of suicidal behavior. We reviewed the scientific literature concerning cytokines related to suicidal ideation, suicidal behavior and suicide, and surveyed clinical and neurobiological factors associated with cytokine levels that may modulate effects of inflammation on suicide risk. Methods We searched PubMed, Embase, Scopus and PsycINFO for relevant studies published from 1980 through February, 2015. Papers were included if they were written in English and focused on cytokine measurements in patients with suicidal behaviors. Results The literature search yielded 22 studies concerning cytokines and suicidal ideation, suicide attempts or suicide completion. The most consistent finding was elevated interleukin (IL)-6, found in 8 out of 14 studies, in CSF, blood, and postmortem brain. In one study, IL-6 in CSF was also found to be higher in violent than nonviolent attempters and to correlate with future suicide completion. Low plasma IL-2 was observed in 2 studies of suicide attempters, while divergent results were seen for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, IL-4, and soluble Il-2 receptors. Conclusions Given the complexity suggested by the heterogenous cytokine findings, putative mediators and moderators of inflammation on suicidal behavior merit further study. Elevated IL-6 was the most robust cytokine finding, associated with suicidal ideation and both nonfatal suicide attempts and suicides. Future studies should evaluate the predictive value of high IL-6, consider how this may alter brain function to impact suicidal behavior, and explore the potential beneficial effects of reducing IL-6 on suicide risk. PMID:26546783

Immune escape strategies of malaria parasites

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Pollyanna Stephanie Gomes

2016-10-01

Full Text Available Malaria is one of the most life-threatening infectious diseases worldwide. Immunity to malaria is slow and short-lived despite the repeated parasite exposure in endemic areas. Malaria parasites have evolved refined machinery to evade the immune system based on a range of genetic changes that include allelic variation, biomolecular exposure of proteins and intracellular replication. All of these features increase the probability of survival in both mosquitoes and the vertebrate host. Plasmodium species escape from the first immunological trap in its invertebrate vector host, the Anopheles mosquitoes. The parasites have to pass through various immunological barriers within the mosquito such as anti-microbial molecules and the mosquito microbiota in order to achieve successful transmission to the vertebrate host. Within these hosts, Plasmodium species employ various immune evasion strategies during different life cycle stages. Parasite persistence against the vertebrate immune response depends on the balance among virulence factors, pathology, metabolic cost of the host immune response, and the parasites ability to evade the immune response. In this review we discuss the strategies that Plasmodium parasites use to avoid the vertebrate host immune system and how they promote successful infection and transmission.

Cytokine accumulation in osteitis fibrosa of renal osteodystrophy

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Duarte M.E.L.

2002-01-01

Full Text Available Bone marrow fibrosis occurs in association with a number of pathological states. Despite the extensive fibrosis that sometimes characterizes renal osteodystrophy, little is known about the factors that contribute to marrow accumulation of fibrous tissue. Because circulating cytokines are elevated in uremia, possibly in response to elevated parathyroid hormone levels, we have examined bone biopsies from 21 patients with end-stage renal disease and secondary hyperparathyroidism. Bone sections were stained with antibodies to human interleukin-1alpha (IL-1alpha, IL-6, IL-11, tumor necrosis factor-alpha (TNF-alpha and transforming growth factor-ß (TGF-ß using an undecalcified plastic embedding method. Intense staining for IL-1alpha, IL-6, TNF-alpha and TGF-ß was evident within the fibrotic tissue of the bone marrow while minimal IL-11 was detected. The extent of cytokine deposition corresponded to the severity of fibrosis, suggesting their possible involvement in the local regulation of the fibrotic response. Because immunoreactive TGF-ß and IL-6 were also detected in osteoblasts and osteocytes, we conclude that selective cytokine accumulation may have a role in modulating bone and marrow cell function in parathyroid-mediated uremic bone disease.

Intestinal parasitic infections in HIV/AIDS patients: epidemiological, nutritional and immunological aspects

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FAM Amâncio

2012-01-01

Full Text Available This study applied a socioeconomic questionnaire designed to evaluate the frequency of intestinal parasites and characterize epidemiological, nutritional, and immunological variables in 105 HIV/AIDS patients - with and without parasitic infections, attending the Day Hospital in Botucatu, UNESP, from 2007 to 2008. Body mass index was calculated and the following tests performed: parasitological stool examinations; eosinophil, IgE, CD4+ T and CD8+ T lymphocyte cell counts; albumin test; viral load measure; and TNF-α, IFN-γ, IL-2, IL-5 and IL-10 cytokine levels. Results were positive for parasitic intestinal infections in 12.4% of individuals. Most patients had good socioeconomic conditions with basic sanitation, urban dwellings, treated water supply and sewage, good nutritional and immunological status and were undergoing HAART. Parasites were found at the following frequencies: Entamoeba - five patients (38.5%, Giardia lamblia - four (30.7%, Blastocystis hominis - three (23.0%, Endolimax nana - two (15.4%, and Ascaris lumbricoides - one (7.7%. There were no significant differences between the two groups for eosinophils, albumin, IgE, CD4+ T and CD8+ T lymphocytes, INF-γ, IL-2, or IL-10. Most patients also showed undetectable viral load levels. Significant differences were found for TNF-α and IL-5. These results show the importance of new studies on immunodeficient individuals to increase understanding of such variables.

Covalent immobilization of stem cell factor and stromal derived factor 1α for in vitro culture of hematopoietic progenitor cells.

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Cuchiara, Maude L; Horter, Kelsey L; Banda, Omar A; West, Jennifer L

2013-12-01

Hematopoietic stem cells (HSCs) are currently utilized in the treatment of blood diseases, but widespread application of HSC therapeutics has been hindered by the limited availability of HSCs. With a better understanding of the HSC microenvironment and the ability to precisely recapitulate its components, we may be able to gain control of HSC behavior. In this work we developed a novel, biomimetic PEG hydrogel material as a substrate for this purpose and tested its potential with an anchorage-independent hematopoietic cell line, 32D clone 3 cells. We immobilized a fibronectin-derived adhesive peptide sequence, RGDS; a cytokine critical in HSC self-renewal, stem cell factor (SCF); and a chemokine important in HSC homing and lodging, stromal derived factor 1α (SDF1α), onto the surfaces of poly(ethylene glycol) (PEG) hydrogels. To evaluate the system's capabilities, we observed the effects of the biomolecules on 32D cell adhesion and morphology. We demonstrated that the incorporation of RGDS onto the surfaces promotes 32D cell adhesion in a dose-dependent fashion. We also observed an additive response in adhesion on surfaces with RGDS in combination with either SCF or SDF1α. In addition, the average cell area increased and circularity decreased on gel surfaces containing immobilized SCF or SDF1α, indicating enhanced cell spreading. By recapitulating aspects of the HSC microenvironment using a PEG hydrogel scaffold, we have shown the ability to control the adhesion and spreading of the 32D cells and demonstrated the potential of the system for the culture of primary hematopoietic cell populations. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Benzoxazole derivatives suppress lipopolysaccharide-induced mast cell activation.

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Cho, Kyung-Ah; Park, Minhwa; Kim, Yu-Hee; Choo, Hea-Young Park; Lee, Kyung Ho

2018-05-01

Mast cells are central regulators of allergic inflammation that function by releasing various proallergic inflammatory mediators, including histamine, eicosanoids and proinflammatory cytokines. Occasionally, bacterial infections may initiate or worsen allergic inflammation. A number of studies have indicated that activation of lipoxygenase in mast cells positive regulates allergic inflammatory responses by generating leukotrienes and proinflammatory cytokines. In the present study, the effects of benzoxazole derivatives on the lipopolysaccharide (LPS)‑induced expression of proinflammatory cytokines, production of histamine and surface expression of co‑stimulatory molecules on bone marrow-derived mast cells (BMMCs) were studied. The benzoxazole derivatives significantly reduced the expression of interleukin (IL)‑1β, IL‑6, IL‑13, tumor necrosis factor‑α, perilipin (PLIN) 2, and PLIN3 in BMMCs treated with LPS. Furthermore, histamine production was suppressed in BMMCs treated with LPS, or treated with phorbol-12-myristate-13-acetate/ionomycin. Benzoxazole derivatives marginally affected the surface expression of cluster of differentiation (CD)80 and CD86 on BMMCs in the presence of LPS, although LPS alone did not increase the expression of those proteins. Therefore, benzoxazole derivatives inhibited the secretion of proinflammatory cytokines in mast cells and may be potential candidate anti‑allergic agents to suppress mast cell activation.

Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice

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Dantzer Robert

2011-02-01

Full Text Available Abstract Exogenous administration of insulin-like growth factor (IGF-I has anti-depressant properties in rodent models of depression. However, nothing is known about the anti-depressant properties of IGF-I during inflammation, nor have mechanisms by which IGF-I alters behavior following activation of the innate immune system been clarified. We hypothesized that central IGF-I would diminish depressive-like behavior on a background of an inflammatory response and that it would do so by inducing expression of the brain-derived neurotrophic factor (BDNF while decreasing pro-inflammatory cytokine expression in the brain. IGF-I (1,000 ng was administered intracerebroventricularly (i.c.v. to CD-1 mice. Mice were subsequently given lipopolysaccharide i.c.v. (LPS, 10 ng. Sickness and depressive-like behaviors were assessed followed by analysis of brain steady state mRNA expression. Central LPS elicited typical transient signs of sickness of mice, including body weight loss, reduced feed intake and decreased social exploration toward a novel juvenile. Similarly, LPS increased time of immobility in the tail suspension test (TST. Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS. To elucidate the mechanisms underlying the anti-depressant action of IGF-I, we quantified steady-state mRNA expression of inflammatory mediators in whole brain using real-time RT-PCR. LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß, tumor necrosis factor-(TNFα, inducible nitric oxide synthase (iNOS and glial fibrillary acidic protein (GFAP. Moreover, IGF-I increased expression of BDNF. These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity. These actions of IGF-I parallel its ability to diminish depressive-like behavior.

Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice

Science.gov (United States)

2011-01-01

Exogenous administration of insulin-like growth factor (IGF)-I has anti-depressant properties in rodent models of depression. However, nothing is known about the anti-depressant properties of IGF-I during inflammation, nor have mechanisms by which IGF-I alters behavior following activation of the innate immune system been clarified. We hypothesized that central IGF-I would diminish depressive-like behavior on a background of an inflammatory response and that it would do so by inducing expression of the brain-derived neurotrophic factor (BDNF) while decreasing pro-inflammatory cytokine expression in the brain. IGF-I (1,000 ng) was administered intracerebroventricularly (i.c.v.) to CD-1 mice. Mice were subsequently given lipopolysaccharide i.c.v. (LPS, 10 ng). Sickness and depressive-like behaviors were assessed followed by analysis of brain steady state mRNA expression. Central LPS elicited typical transient signs of sickness of mice, including body weight loss, reduced feed intake and decreased social exploration toward a novel juvenile. Similarly, LPS increased time of immobility in the tail suspension test (TST). Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS. To elucidate the mechanisms underlying the anti-depressant action of IGF-I, we quantified steady-state mRNA expression of inflammatory mediators in whole brain using real-time RT-PCR. LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß), tumor necrosis factor-(TNF)α, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP). Moreover, IGF-I increased expression of BDNF. These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity. These actions of IGF-I parallel its ability to diminish depressive-like behavior. PMID:21306618

Novel methods of cytokine detection: Real-time PCR, ELISPOT, and intracellular cytokine staining

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Eliza Turlej

2009-05-01

Full Text Available Cytokines are small hormone-like proteins that play important roles in immune system control. Cytokines regulate the proliferation and differentiation of cells and hematopoiesis and act as mediators in the inflammatory reaction. Changes in cytokine levels are found in many diseases, such as sepsis, bowel inflammatory disease, autoimmune diseases, as well as graft-versus-host disease. Cytokines levels can be detected using in vivo, in vitro, and ex vivo techniques. The level of cytokine produced can be measured by immunoenzymatic test (ELISA in supernatant after cell culture with the addition of stimulant and in plasma by techniques that measure the level of cytokine secretion in cells (e.g. immunohistochemical staining, ELISPOT, and intracellular cytokine staining, and by molecular biological methods (RPA, real-time PCR, in situ hybridization, and Northern blot. Detection of cytokine mRNA in tissues is useful in the direct determination of heterogenic populations of cytokine-producing cells. Nowadays the most frequently used methods for measuring cytokine level are ELISPOT, intracellular cytokine staining with flow cytometry detection, and real-time PCR. These methods have an important clinical role in vaccine efficacy, in viral, bacterial, and verminous diagnostics, and in determining the efficacy of cancer treatment.

Accumulation of pro-cancer cytokines in the plasma fraction of stored packed red cells.

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Benson, Douglas D; Beck, Adam W; Burdine, Marie S; Brekken, Rolf; Silliman, Christopher C; Barnett, Carlton C

2012-03-01

Perioperative blood transfusion has been linked to decreased survival in pancreatic cancer; however, the exact causal mechanism has not been elucidated. Allogeneic transfusions are known to expose patients to foreign cells and lipid mediators. We hypothesize that stored packed red cells (pRBCs) contain pro-cancer cytokines that augment tumor progression. We analyzed the plasma fraction of stored pRBCs for pro-cancer cytokines and evaluated the affect of both storage time and leukocyte reduction on these mediators. Chemiarray™ analysis for pro-cancer cytokines was performed on the acellular plasma fraction of stored leukocyte-reduced (LR) and non-leukocyte-reduced (NLR) pRBCs at day 1 (D.1-fresh) and day 42 (D.42-outdate) of storage. Elevated expression of monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), angiogenin, tumor necrosis factor-alpha (TNF-α), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) was found. Specific enzyme-linked immunosorbent assay was performed for each of these factors in LR and NLR blood at D.1, day 28, and D.42. Data were analyzed by ANOVA. A p value ≤ 0.05 was considered significant; N ≥ 4 per group. Migration assays were performed using inhibitors of EGF (gefitinib) and PDGF (imatinib) on murine pancreatic adenocarcinoma cells (Pan02) exposed to D.1 and D.42 LR and NLR plasma. Proliferation assays were performed on Pan02 cells to test the inhibition of PDGF. MCP-1 levels increased with storage time in LR blood, 86.3 ± 6.3 pg/ml at D.1 vs. 121.2 ± 6.1 pg/ml at D.42 (p = 0.007), and NLR blood, 78.2 ± 7.3 pg/ml at D.1 vs. 647.8 ± 220.7 pg/ml at D.42 (p = 0.02). RANTES levels are lower in LR compared to NLR stored blood, 3.0 ± 1.9 vs. 15.8 ± 0.7 pg/ml at D.42 (p Pro-cancer cytokines that can augment tumor progression were identified in pRBCs. Some of these factors are present in fresh blood. The soluble factors identified herein may represent

Platelet-derived growth factor inhibits platelet activation in heparinized whole blood.

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Selheim, F; Holmsen, H; Vassbotn, F S

1999-08-15

We previously have demonstrated that human platelets have functionally active platelet-derived growth factor alpha-receptors. Studies with gel-filtered platelets showed that an autocrine inhibition pathway is transduced through this tyrosine kinase receptor during platelet activation. The physiological significance of this inhibitory effect of platelet-derived growth factor on gel-filtered platelets activation is, however, not known. In the present study, we investigated whether platelet-derived growth factor inhibits platelet activation under more physiological conditions in heparinized whole blood, which represents a more physiological condition than gel-filtered platelets. Using flow cytometric assays, we demonstrate here that platelet-derived growth factor inhibits thrombin-, thrombin receptor agonist peptide SFLLRN-, and collagen-induced platelet aggregation and shedding of platelet-derived microparticles from the platelet plasma membrane during platelet aggregation in stirred heparinized whole blood. The inhibitory effect of platelet-derived growth factor was dose dependent. However, under nonaggregating conditions (no stirring), we could not demonstrate any significant effect of platelet-derived growth factor on thrombin- and thrombin receptor agonist peptide-induced platelet surface expression of P-selectin. Our results demonstrate that platelet-derived growth factor appears to be a true antithrombotic agent only under aggregating conditions in heparinized whole blood.

Paternity-parasitism trade-offs: a model and test of host-parasite cooperation in an avian conspecific brood parasite.

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Lyon, Bruce E; Hochachka, Wesley M; Eadie, John M

2002-06-01

Efforts to evaluate the evolutionary and ecological dynamics of conspecific brood parasitism in birds and other animals have focused on the fitness costs of parasitism to hosts and fitness benefits to parasites. However, it has been speculated recently that, in species with biparental care, host males might cooperate with parasitic females by allowing access to the host nest in exchange for copulations. We develop a cost-benefit model to explore the conditions under which such host-parasite cooperation might occur. When the brood parasite does not have a nest of her own, the only benefit to the host male is siring some of the parasitic eggs (quasi-parasitism). Cooperation with the parasite is favored when the ratio of host male paternity of his own eggs relative to his paternity of parasitic eggs exceeds the cost of parasitism. When the brood parasite has a nest of her own, a host male can gain additional, potentially more important benefits by siring the high-value, low-cost eggs laid by the parasite in her own nest. Under these conditions, host males should be even more likely to accept parasitic eggs in return for copulations with the parasitic female. We tested these predictions for American coots (Fulica americana), a species with a high frequency of conspecific brood parasitism. Multilocus DNA profiling indicated that host males did not sire any of the parasitic eggs laid in host nests, nor did they sire eggs laid by the parasite in her own nest. We used field estimates of the model parameters from a four-year study of coots to predict the minimum levels of paternity required for the costs of parasitism to be offset by the benefits of mating with brood parasites. Observed levels of paternity were significantly lower than those predicted under a variety of assumptions, and we reject the hypothesis that host males cooperated with parasitic females. Our model clarifies the specific costs and benefits that influence host-parasite cooperation and, more generally

Evaluation of MSCTA for parasitic blood supply in hepatic carcinoma

International Nuclear Information System (INIS)

Yang Weihong; Liu Pengcheng; Liang Shanhu; Yuan Zhidong; Yu Hongjian; Deng Qianhua

2008-01-01

Objective: To evaluate the multi-slice spiral computer tomography for hepatocarcinoma parasitic blood supply, and analyze the mechanism of the parasitic angiogenesis. Methods: Forty cases confirmed by DSA and confirmed with the existence of parasitic blood supply through manifestations of MSCTA were retrospectively analized. Comparing the coincidence of different reconstruction modalities of MSCTA and DSA in displaying the parasitic blood supply and then to assess the characteristics of MSCTA of the cases with existing parasitic blood supply. Results: DSA displayed parasitic blood supply in 50 arterial rami and MSCTA displayed only 40 rami, with positive rate of 80%. The best display could be reached by the reconstruction of combining MIP and VRT. This kind of reconstruction revealed not only the parasitic blood supply but also the peripheral sites of the primary focci with average length of diameter of 6.9 cm. Conclusions: MSCTA possesses nearly the same capability with DSA in demonstrating the parasitic blood supply to primary hepatic carcinoma, therefore it could be utilized in evaluation of intervention therapy and surgical, operation and transplantation. The primary hepatic carcinoma with this kind of parasitic blood supply is always located at the bare were of liver and ligmentarn suspensoram together with direct invasion of nearby organs with adhesions may contribute the main factor of parasitic blood supply, furthermore the repetition of TACE inducing the decrease of collateral circulation may also be the another major factor. (authors)

Evaluation of MSCTA for parasitic blood supply in hepatic carcinoma

Energy Technology Data Exchange (ETDEWEB)

Weihong, Yang; Pengcheng, Liu; Shanhu, Liang; Zhidong, Yuan; Hongjian, Yu; Qianhua, Deng [Department of Radiology, Shenzhen Hospital of Beijing College, Guangdong, Shenzhen (China)

2008-09-15

Objective: To evaluate the multi-slice spiral computer tomography for hepatocarcinoma parasitic blood supply, and analyze the mechanism of the parasitic angiogenesis. Methods: Forty cases confirmed by DSA and confirmed with the existence of parasitic blood supply through manifestations of MSCTA were retrospectively analized. Comparing the coincidence of different reconstruction modalities of MSCTA and DSA in displaying the parasitic blood supply and then to assess the characteristics of MSCTA of the cases with existing parasitic blood supply. Results: DSA displayed parasitic blood supply in 50 arterial rami and MSCTA displayed only 40 rami, with positive rate of 80%. The best display could be reached by the reconstruction of combining MIP and VRT. This kind of reconstruction revealed not only the parasitic blood supply but also the peripheral sites of the primary focci with average length of diameter of 6.9 cm. Conclusions: MSCTA possesses nearly the same capability with DSA in demonstrating the parasitic blood supply to primary hepatic carcinoma, therefore it could be utilized in evaluation of intervention therapy and surgical, operation and transplantation. The primary hepatic carcinoma with this kind of parasitic blood supply is always located at the bare were of liver and ligmentarn suspensoram together with direct invasion of nearby organs with adhesions may contribute the main factor of parasitic blood supply, furthermore the repetition of TACE inducing the decrease of collateral circulation may also be the another major factor. (authors)

Bacterial and parasitic diseases of parrots.

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Doneley, Robert J T

2009-09-01

As wild-caught birds become increasingly rare in aviculture, there is a corresponding decline in the incidence of bacterial and parasitic problems and an increase in the recognition of the importance of maintaining health through better nutrition and husbandry. Nevertheless, the relatively close confines of captivity mean an increased pathogen load in the environment in which companion and aviary parrots live. This increased pathogen load leads to greater exposure of these birds to bacteria and parasites, and consequently a greater risk of infection and disease. This article discusses bacterial and parasitic infections in companion and aviary parrots. It includes the origins, pathogens, diagnosis, treatment, and some of the associated risk factors.

Splenectomy enhances the therapeutic effect of adipose tissue-derived mesenchymal stem cell infusion on cirrhosis rats.

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Tang, Wei-Ping; Akahoshi, Tomohiko; Piao, Jing-Shu; Narahara, Sayoko; Murata, Masaharu; Kawano, Takahito; Hamano, Nobuhito; Ikeda, Tetsuo; Hashizume, Makoto

2016-08-01

Clinical studies suggest that splenectomy improves liver function in cirrhotic patients, but the influence of splenectomy on stem cell transplantation is poorly understood. This study investigated the effect of splenectomy on stem cell infusion and elucidated its mechanism. Rat adipose tissue-derived mesenchymal stem cells were infused into cirrhosis rats with or without splenectomy, followed by the assessment of the in vivo distribution of stem cells and pathological changes. Stromal cell-derived factor-1 and hepatocyte growth factor expression were also investigated in splenectomized cirrhosis patients and rats. Splenectomy, prior to cell infusion, improved liver function and suppressed fibrosis progression more efficiently than cell infusion alone in the experimental cirrhosis model. Stromal cell-derived factor-1 and hepatocyte growth factor levels after splenectomy were increased in patients and rats. These upregulated cytokines significantly facilitated stem cell motility, migration and proliferation in vitro. C-X-C chemokine receptor type 4 neutralization weakened the promotion of cell migration by these cytokines. The infused cells integrated into liver fibrosis septa and participated in regeneration more efficiently in splenectomized rats. Direct coculture with stem cells led to inhibition of hepatic stellate cell proliferation. In addition, hepatocyte growth factor induced hepatic stellate cell apoptosis via the c-jun N-terminal kinase-p53 pathway. Splenectomy prior to cell infusion enhanced the therapeutic effect of stem cells on cirrhosis, which involved upregulation of stromal cell-derived factor-1 and hepatocyte growth factor after splenectomy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cytokine Correlations in Youth with Tic Disorders

Science.gov (United States)

Parker-Athill, E. Carla; Ehrhart, Jared; Tan, Jun

2015-01-01

Abstract Background: Studies have noted immunological disruptions in patients with tic disorders, including increased serum cytokine levels. This study aimed to determine whether or not cytokine levels could be correlated with tic symptom severity in patients with a diagnosed tic disorder. Methods: Twenty-one patients, ages 4–17 years (average 10.63±2.34 years, 13 males), with a clinical diagnosis of Tourette's syndrome (TS) or chronic tic disorder (CTD), were selected based on having clinic visits that coincided with a tic symptom exacerbation and a remission. Ratings of tic severity were assessed using the Yale Global Tic Severity Scale (YGTSS) and serum cytokine levels (interleukin [IL]-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and granulocyte macrophage-colony stimulating factor [GM-CSF]) were measured using Luminex xMAP technology. Results: During tic symptom exacerbation, patients had higher median serum TNF-α levels (z=−1.962, p=0.05), particularly those on antipsychotics (U=9.00, p=0.033). Increased IL-13 was also associated with antipsychotic use during exacerbation (U=4.00, p=0.043) despite being negatively correlated to tic severity scores (ρ=−0.599, p=018), whereas increased IL-5 was associated with antibiotic use (U=6.5, p=0.035). During tic symptom remission, increased serum IL-4 levels were associated with antipsychotic (U=6.00, p=0.047) and antibiotic (U=1.00, p=0.016) use, whereas increased IL-12p70 (U=4.00, p=0.037) was associated with antibiotic use. Conclusions: These findings suggest a role for cytokine dysregulation in the pathogenesis of tic disorders. It also points toward the mechanistic involvement and potential diagnostic utility of cytokine monitoring, particularly TNF-α levels. Larger, systematic studies are necessary to further delineate the role of cytokines and medication influences on immunological profiling in tic disorders. PMID:25658821

Cytokine correlations in youth with tic disorders.

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Parker-Athill, E Carla; Ehrhart, Jared; Tan, Jun; Murphy, Tanya K

2015-02-01

Studies have noted immunological disruptions in patients with tic disorders, including increased serum cytokine levels. This study aimed to determine whether or not cytokine levels could be correlated with tic symptom severity in patients with a diagnosed tic disorder. Twenty-one patients, ages 4-17 years (average 10.63±2.34 years, 13 males), with a clinical diagnosis of Tourette's syndrome (TS) or chronic tic disorder (CTD), were selected based on having clinic visits that coincided with a tic symptom exacerbation and a remission. Ratings of tic severity were assessed using the Yale Global Tic Severity Scale (YGTSS) and serum cytokine levels (interleukin [IL]-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and granulocyte macrophage-colony stimulating factor [GM-CSF]) were measured using Luminex xMAP technology. During tic symptom exacerbation, patients had higher median serum TNF-α levels (z=-1.962, p=0.05), particularly those on antipsychotics (U=9.00, p=0.033). Increased IL-13 was also associated with antipsychotic use during exacerbation (U=4.00, p=0.043) despite being negatively correlated to tic severity scores (ρ=-0.599, p=018), whereas increased IL-5 was associated with antibiotic use (U=6.5, p=0.035). During tic symptom remission, increased serum IL-4 levels were associated with antipsychotic (U=6.00, p=0.047) and antibiotic (U=1.00, p=0.016) use, whereas increased IL-12p70 (U=4.00, p=0.037) was associated with antibiotic use. These findings suggest a role for cytokine dysregulation in the pathogenesis of tic disorders. It also points toward the mechanistic involvement and potential diagnostic utility of cytokine monitoring, particularly TNF-α levels. Larger, systematic studies are necessary to further delineate the role of cytokines and medication influences on immunological profiling in tic disorders.

Social Parasites

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Lopez, Miguel A.; Nguyen, HoangKim T.; Oberholzer, Michael; Hill, Kent L.

2011-01-01

Summary of recent advances Protozoan parasites cause tremendous human suffering worldwide, but strategies for therapeutic intervention are limited. Recent studies illustrate that the paradigm of microbes as social organisms can be brought to bear on questions about parasite biology, transmission and pathogenesis. This review discusses recent work demonstrating adaptation of social behaviors by parasitic protozoa that cause African sleeping sickness and malaria. The recognition of social behavior and cell-cell communication as a ubiquitous property of bacteria has transformed our view of microbiology, but protozoan parasites have not generally been considered in this context. Works discussed illustrate the potential for concepts of sociomicrobiology to provide insight into parasite biology and should stimulate new approaches for thinking about parasites and parasite-host interactions. PMID:22020108

Antidiabetic Effect of Brain-Derived Neurotrophic Factor and Its Association with Inflammation in Type 2 Diabetes Mellitus

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Ceren Eyileten

2017-01-01

Full Text Available Brain-derived neurotrophic factor (BDNF is a neurotrophin, which plays an important role in the central nervous system, and systemic or peripheral inflammatory conditions, such as acute coronary syndrome and type 2 diabetes mellitus (T2DM. BDNF is also expressed in several nonneuronal tissues, and platelets are the major source of peripheral BDNF. Here, we reviewed the potential role of BDNF in platelet reactivity in T2DM and its association with selected inflammatory and platelet activation mediators. Besides that, we focused on adipocytokines such as leptin, resistin, and adiponectin which are considered to take part in inflammation and both lipid and glucose metabolism in diabetic patients as previous studies showed the relation between adipocytokines and BDNF. We also reviewed the evidences of the antidiabetic effect of BDNF and the association with circulating inflammatory cytokines in T2DM.

Environmentally transmitted parasites: Host-jumping in a heterogeneous environment.

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Caraco, Thomas; Cizauskas, Carrie A; Wang, Ing-Nang

2016-05-21

Groups of chronically infected reservoir-hosts contaminate resource patches by shedding a parasite׳s free-living stage. Novel-host groups visit the same patches, where they are exposed to infection. We treat arrival at patches, levels of parasite deposition, and infection of the novel host as stochastic processes, and derive the expected time elapsing until a host-jump (initial infection of a novel host) occurs. At stationarity, mean parasite densities are independent of reservoir-host group size. But within-patch parasite-density variances increase with reservoir group size. The probability of infecting a novel host declines with parasite-density variance; consequently larger reservoir groups extend the mean waiting time for host-jumping. Larger novel-host groups increase the probability of a host-jump during any single patch visit, but also reduce the total number of visits per unit time. Interaction of these effects implies that the waiting time for the first infection increases with the novel-host group size. If the reservoir-host uses resource patches in any non-uniform manner, reduced spatial overlap between host species increases the waiting time for host-jumping. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cytokines as cellular communicators

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R. Debets

1996-01-01

Full Text Available Cytokines and their receptors are involved in the pathophysiology of many diseases. Here we present a detailed review on cytokines, receptors and signalling routes, and show that one important lesson from cytokine biology is the complex and diverse regulation of cytokine activity. The activity of cytokines is controlled at the level of transcription, translation, storage, processing, posttranslational modification, trapping, binding by soluble proteins, and receptor number and/or function. Translation of this diverse regulation in strategies aimed at the control of cytokine activity will result in the development of more specific and selective drugs to treat diseases.

Exploring the host parasitism of the migratory plant-parasitic nematode Ditylenchus destuctor by expressed sequence tags analysis.

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Huan Peng

Full Text Available The potato rot nematode, Ditylenchus destructor, is a very destructive nematode pest on many agriculturally important crops worldwide, but the molecular characterization of its parasitism of plant has been limited. The effectors involved in nematode parasitism of plant for several sedentary endo-parasitic nematodes such as Heterodera glycines, Globodera rostochiensis and Meloidogyne incognita have been identified and extensively studied over the past two decades. Ditylenchus destructor, as a migratory plant parasitic nematode, has different feeding behavior, life cycle and host response. Comparing the transcriptome and parasitome among different types of plant-parasitic nematodes is the way to understand more fully the parasitic mechanism of plant nematodes. We undertook the approach of sequencing expressed sequence tags (ESTs derived from a mixed stage cDNA library of D. destructor. This is the first study of D. destructor ESTs. A total of 9800 ESTs were grouped into 5008 clusters including 3606 singletons and 1402 multi-member contigs, representing a catalog of D. destructor genes. Implementing a bioinformatics' workflow, we found 1391 clusters have no match in the available gene database; 31 clusters only have similarities to genes identified from D. africanus, the most closely related species to D. destructor; 1991 clusters were annotated using Gene Ontology (GO; 1550 clusters were assigned enzyme commission (EC numbers; and 1211 clusters were mapped to 181 KEGG biochemical pathways. 22 ESTs had similarities to reported nematode effectors. Interestedly, most of the effectors identified in this study are involved in host cell wall degradation or modification, such as 1,4-beta-glucanse, 1,3-beta-glucanse, pectate lyase, chitinases and expansin, or host defense suppression such as calreticulin, annexin and venom allergen-like protein. This result implies that the migratory plant-parasitic nematode D. destructor secrets similar effectors to

Enhanced Inhibitory Effect of Ultra-Fine Granules of Red Ginseng on LPS-induced Cytokine Expression in the Monocyte-Derived Macrophage THP-1 Cells

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Hong-Yeoul Kim

2008-08-01

Full Text Available Red ginseng is one of the most popular traditional medicines in Korea because its soluble hot-water extract is known to be very effective on enhancing immunity as well as inhibiting inflammation. Recently, we developed a new technique, called the HACgearshift system, which can pulverize red ginseng into the ultra-fine granules ranging from 0.2 to 7.0 μm in size. In this study, the soluble hot-water extract of those ultra-fine granules of red ginseng (URG was investigated and compared to that of the normal-sized granules of red ginseng (RG. The high pressure liquid chromatographic analyses of the soluble hot-water extracts of both URG and RG revealed that URG had about 2-fold higher amounts of the ginsenosides, the biologically active components in red ginseng, than RG did. Using quantitative RT-PCR, cytokine profiling against the Escherichia coli lipopolysaccharide (LPS in the monocyte-derived macrophage THP-1 cells demonstrated that the URG-treated cells showed a significant reduction in cytokine expression than the RG-treated ones. Transcription expression of the LPS-induced cytokines such as TNF-α, IL-1β, IL-6, IL-8, IL-10, and TGF-β was significantly inhibited by URG compared to RG. These results suggest that some biologically active and soluble components in red ginseng can be more effectively extracted from URG than RG by standard hot-water extraction.

Plasma cytokines in acute stroke

DEFF Research Database (Denmark)

Christensen, Hanne Krarup; Boysen, Gudrun; Christensen, Erik

2011-01-01

GOALS: The aim of this study was to test the relations between plasma cytokines and the clinical characteristics, course, and risk factors in acute stroke. PATIENTS AND METHODS: The analysis was based on 179 patients with acute stroke included within 24 hours of stroke onset. On inclusion and 3...... months later plasma levels of interleukin 1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interleukin-1 receptor antagonist (IL-1RA), interleukin 6 (IL-6), interleukin 10 (IL-10), soluble tumor necrosis factor receptor 1 (sTNF-R1), and soluble tumor necrosis factor receptor 2 (sTNF-R2) were...

Mechanisms of cellular invasion by intracellular parasites.

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Walker, Dawn M; Oghumu, Steve; Gupta, Gaurav; McGwire, Bradford S; Drew, Mark E; Satoskar, Abhay R

2014-04-01

Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.

Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia.

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Delgado, R; Carlin, A; Airaghi, L; Demitri, M T; Meda, L; Galimberti, D; Baron, P; Lipton, J M; Catania, A

1998-06-01

Inflammatory processes contribute to neurodegenerative disease, stroke, encephalitis, and other central nervous system (CNS) disorders. Activated microglia are a source of cytokines and other inflammatory agents within the CNS and it is therefore important to control glial function in order to preserve neural cells. Melanocortin peptides are pro-opiomelanocortin-derived amino acid sequences that include alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH). These peptides have potent and broad anti-inflammatory effects. We tested effects of alpha-MSH (1-13), alpha-MSH (11-13), and ACTH (1-24) on production of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO) in a cultured murine microglial cell line (N9) stimulated with lipopolysaccharide (LPS) plus interferon gamma (IFN-gamma). Melanocortin peptides inhibited production of these cytokines and NO in a concentration-related fashion, probably by increasing intracellular cAMP. When stimulated with LPS + IFN-gamma, microglia increased release of alpha-MSH. Production of TNF-alpha, IL-6, and NO was greater in activated microglia after innmunoneutralization of endogenous alpha-MSH. The results suggest that alpha-MSH is an autocrine factor in microglia. Because melanocortin peptides inhibit production of pro-inflammatory mediators by activated microglia they might be useful in treatment of inflammatory/degenerative brain disorders.

Parasites and poverty: the case of schistosomiasis.

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King, Charles H

2010-02-01

Simultaneous and sequential transmission of multiple parasites, and their resultant overlapping chronic infections, are facts of life in many underdeveloped rural areas. These represent significant but often poorly measured health and economic burdens for affected populations. For example, the chronic inflammatory process associated with long-term schistosomiasis contributes to anaemia and undernutrition, which, in turn, can lead to growth stunting, poor school performance, poor work productivity, and continued poverty. To date, most national and international programs aimed at parasite control have not considered the varied economic and ecological factors underlying multi-parasite transmission, but some are beginning to provide a coordinated approach to control. In addition, interest is emerging in new studies for the re-evaluation and recalibration of the health burden of helminthic parasite infection. Their results should highlight the strong potential of integrated parasite control in efforts for poverty reduction. Copyright 2009 Elsevier B.V. All rights reserved.

A cytokine axis regulates elastin formation and degradation

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Sproul, Erin P.; Argraves, W. Scott

2013-01-01

Underlying the dynamic regulation of tropoelastin expression and elastin formation in development and disease are transcriptional and post-transcriptional mechanisms that have been the focus of much research. Of particular importance is the cytokine–governed elastin regulatory axis in which the pro-elastogenic activities of transforming growth factor β-1 (TGFβ1) and insulin-like growth factor-I (IGF-I) are opposed by anti-elastogenic activities of basic fibroblast growth factor (bFGF/FGF-2), heparin-binding epidermal growth factor-like growth factor (HB-EGF), EGF, PDGF-BB, TGFα, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and noncanonical TGFβ1 signaling. A key mechanistic feature of the regulatory axis is that cytokines influence elastin formation through effects on the cell cycle involving control of cyclin–cyclin dependent kinase complexes and activation of the Ras/MEK/ERK signaling pathway. In this article we provide an overview of the major cytokines/growth factors that modulate elastogenesis and describe the underlying molecular mechanisms for their action on elastin production. PMID:23160093

Modulation by Polypodium leucotomos extract of cytokine patterns in experimental trichomoniasis model

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Nogal-Ruiz J.J.

2003-03-01

Full Text Available The immunomodulating effects of Anapsos®, an aqueous hydrosoluble extract obtained from the rhizomes of the fern Polypodium leucotomos, on both pathogenicity and cytokine levels in serum (IFN-γ/IL-4 were assayed in a Trichomonas vaginalis experimental model (BALB/c mice infected with 107 trichomonads and examined at day 15 after infection. Doses of 20 mg/kg/day administered for 10 days before the infection with the parasite induced a decrease of the experimental pathogenicity approximately 10-20 % compared to controls. Gross histopathologic changes at abdominal organs and mortality rate, as a consequence of pathogenicity of the protozoa and the immune response of the host, were evaluated. IFN-y and IL-4 cytokines were determined on days -5, 0, 5, 10, and 15 postinfection by indirect ELISA. Treatment with PAL before infection modulates and downregulates the IFN-γ concentration, while anticipates and upregulates the IL-4 level. The assays performed have showed the utility of the murine model of experimental trichomoniasis for the evaluation of immunomodulatory activity of synthetic or natural products.

African Trypanosomiasis-Associated Anemia: The Contribution of the Interplay between Parasites and the Mononuclear Phagocyte System

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Benoit Stijlemans

2018-02-01

Full Text Available African trypanosomosis (AT is a chronically debilitating parasitic disease of medical and economic importance for the development of sub-Saharan Africa. The trypanosomes that cause this disease are extracellular protozoan parasites that have developed efficient immune escape mechanisms to manipulate the entire host immune response to allow parasite survival and transmission. During the early stage of infection, a profound pro-inflammatory type 1 activation of the mononuclear phagocyte system (MPS, involving classically activated macrophages (i.e., M1, is required for initial parasite control. Yet, the persistence of this M1-type MPS activation in trypanosusceptible animals causes immunopathology with anemia as the most prominent pathological feature. By contrast, in trypanotolerant animals, there is an induction of IL-10 that promotes the induction of alternatively activated macrophages (M2 and collectively dampens tissue damage. A comparative gene expression analysis between M1 and M2 cells identified galectin-3 (Gal-3 and macrophage migration inhibitory factor (MIF as novel M1-promoting factors, possibly acting synergistically and in concert with TNF-α during anemia development. While Gal-3 enhances erythrophagocytosis, MIF promotes both myeloid cell recruitment and iron retention within the MPS, thereby depriving iron for erythropoiesis. Hence, the enhanced erythrophagocytosis and suppressed erythropoiesis lead to anemia. Moreover, a thorough investigation using MIF-deficient mice revealed that the underlying mechanisms in AT-associated anemia development in trypanosusceptible and tolerant animals are quite distinct. In trypanosusceptible animals, anemia resembles anemia of inflammation, while in trypanotolerant animals’ hemodilution, mainly caused by hepatosplenomegaly, is an additional factor contributing to anemia. In this review, we give an overview of how trypanosome- and host-derived factors can contribute to trypanosomosis

The antimicrobial peptide derived from insulin-like growth factor-binding protein 5, AMP-IBP5, regulates keratinocyte functions through Mas-related gene X receptors.

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Chieosilapatham, Panjit; Niyonsaba, François; Kiatsurayanon, Chanisa; Okumura, Ko; Ikeda, Shigaku; Ogawa, Hideoki

2017-10-01

In addition to their microbicidal properties, host defense peptides (HDPs) display various immunomodulatory functions, including keratinocyte production of cytokines/chemokines, proliferation, migration and wound healing. Recently, a novel HDP named AMP-IBP5 (antimicrobial peptide derived from insulin-like growth factor-binding protein 5) was shown to exhibit antimicrobial activity against numerous pathogens, even at concentrations comparable to those of human β-defensins and LL-37. However, the immunomodulatory role of AMP-IBP5 in cutaneous tissue remains unknown. To investigate whether AMP-IBP5 triggers keratinocyte activation and to clarify its mechanism. Production of cytokines/chemokines and growth factors was determined by appropriate ELISA kits. Cell migration was assessed by in vitro wound closure assay, whereas cell proliferation was analyzed using BrdU incorporation assay complimented with XTT assay. MAPK and NF-κB activation was determined by Western blotting. Intracellular cAMP levels were assessed using cAMP enzyme immunoassay kit. Among various cytokines/chemokines and growth factors tested, AMP-IBP5 selectively increased the production of IL-8 and VEGF. Moreover, AMP-IBP5 markedly enhanced keratinocyte migration and proliferation. AMP-IBP5-induced keratinocyte activation was mediated by Mrg X1-X4 receptors with MAPK and NF-κB pathways working downstream, as evidenced by the inhibitory effects of MrgX1-X4 siRNAs and ERK-, JNK-, p38- and NF-κB-specific inhibitors. We confirmed that AMP-IBP5 indeed induced MAPK and NF-κB activation. Furthermore, AMP-IBP5-induced VEGF but not IL-8 production correlated with an increase in intracellular cAMP. Our findings suggest that in addition to its antimicrobial function, AMP-IBP5 might contribute to wound healing process through activation of keratinocytes. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Association between Placental Lesions, Cytokines and Angiogenic Factors in Pregnant Women with Preeclampsia.

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Ingrid C Weel

Full Text Available Preeclampsia (PE is considered the leading cause of maternal and perinatal morbidity and mortality. The placenta seems to play an essential role in this disease, probably due to factors involved in its formation and development. The present study aimed to investigate the association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia (PE. We evaluated 20 normotensive pregnant women, 40 with early-onset PE and 80 with late-onset PE. Placental samples were analyzed for histopathology, immunohistochemistry and determination of granulocyte-macrophage colony-stimulating factor (GM-CSF, interleukin-10 (IL-10, transforming growth factor-beta 1 (TGF-β1, tumor necrosis factor-alpha (TNF-α, placental growth factor (PlGF, vascular endothelial growth factor (VEGF, fms-like tyrosine-kinase-1 (Flt-1 and endoglin (Eng levels. Higher percentages of increased syncytial knots and increased perivillous fibrin deposits, and greater levels of TNF-α, TGF-β1and Flt-1 were detected in placentas from early-onset PE. Levels of IL-10, VEGF and PlGF were decreased in PE versus normotensive placentas. Both the TNF-α/IL-10 and sFlt-1/PlGF ratios were higher in placental homogenate of early-onset PE than late-onset PE and control groups. The more severe lesions and the imbalance between TNF-α/IL-10 and PlGF/sFlt-1 in placentas from early-onset PE allows differentiation of early and late-onset PE and suggests higher placental impairment in early-onset PE.

Syndecan-1 knock-down in decidualized human endometrial stromal cells leads to significant changes in cytokine and angiogenic factor expression patterns

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Krüssel Jan-Steffen

2010-11-01

Full Text Available Abstract Background Successful embryonic implantation depends on a synchronized embryo-maternal dialogue. Chemokines, such as chemokine ligand 1 (CXCL1, play essential roles in the maternal reproductive tract leading to morphological changes during decidualization, mediating maternal acceptance towards the semi-allograft embryo and induction of angiogenesis. Chemokine binding to their classical G-protein coupled receptors is essentially supported by the syndecan (Sdc family of heparan sulfate proteoglycans. The aim of this study was to identify the involvement of Sdc-1 at the embryo-maternal interface regarding changes of the chemokine and angiogenic profile of the decidua during the process of decidualization and implantation in human endometrium. Methods A stable Sdc-1 knock-down was generated in the immortalized human endometrial stromal cell line St-T1 and was named KdS1. The ability of KdS1 to decidualize was proven by Insulin-like growth factor binding 1 (IGFBP1 and prolactin (PRL confirmation on mRNA level before further experiments were carried out. Dot blot protein analyses of decidualized knock-down cells vs non-transfected controls were performed. In order to imitate embryonic implantation, decidualized KdS1 were then incubated with IL-1beta, an embryo secretion product, vs controls. Statistical analyses were performed applying the Student's t-test with p Results The induction of the Sdc-1 knock-down revealed significant changes in cytokine and angiogenic factor expression profiles of dKdS1 vs decidualized controls. Incubation with embryonic IL-1beta altered the expression patterns of KdS1 chemokines and angiogenic factors towards inflammatory-associated molecules and factors involved in matrix regulation. Conclusions Sdc-1 knock-down in human endometrial stroma cells led to fulminant changes regarding cytokine and angiogenic factor expression profiles upon decidualization and imitation of embryonic contact. Sdc-1 appears to play an

Cytokine response during non-cerebral and cerebral malaria: evidence of a failure to control inflammation as a cause of death in African adults

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Yakhya Dieye

2016-05-01

Full Text Available Background. With 214 million cases and 438,000 deaths in 2015, malaria remains one of the deadliest infectious diseases in tropical countries. Several species of the protozoan Plasmodium cause malaria. However, almost all the fatalities are due to Plasmodium falciparum, a species responsible for the severest cases including cerebral malaria. Immune response to Plasmodium falciparum infection is mediated by the production of pro-inflammatory cytokines, chemokines and growth factors whose actions are crucial for the control of the parasites. Following this response, the induction of anti-inflammatory immune mediators downregulates the inflammation thus preventing its adverse effects such as damages to various organs and death. Methods. We performed a retrospective, nonprobability sampling study using clinical data and sera samples from patients, mainly adults, suffering of non-cerebral or cerebral malaria in Dakar, Sénégal. Healthy individuals residing in the same area were included as controls. We measured the serum levels of 29 biomarkers including growth factors, chemokines, inflammatory and anti-inflammatory cytokines. Results. We found an induction of both pro- and anti-inflammatory immune mediators during malaria. The levels of pro-inflammatory biomarkers were higher in the cerebral malaria than in the non-cerebral malaria patients. In contrast, the concentrations of anti-inflammatory cytokines were comparable in these two groups or lower in CM patients. Additionally, four pro-inflammatory biomarkers were significantly increased in the deceased of cerebral malaria compared to the survivors. Regarding organ damage, kidney failure was significantly associated with death in adults suffering of cerebral malaria. Conclusions. Our results suggest that a poorly controlled inflammatory response determines a bad outcome in African adults suffering of cerebral malaria.

Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors.

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Mirjam E Belderbos

Full Text Available Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP or soluble CD14 (sCD14. The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection.

Neonatal Plasma Polarizes TLR4-Mediated Cytokine Responses towards Low IL-12p70 and High IL-10 Production via Distinct Factors

Science.gov (United States)

Belderbos, Mirjam E.; Levy, Ofer; Stalpers, Femke; Kimpen, Jan L.; Meyaard, Linde; Bont, Louis

2012-01-01

Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR) responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs) produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP) or soluble CD14 (sCD14). The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection. PMID:22442690

Richness patterns in the parasite communities of exotic poeciliid fishes.

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Dove, A D

2000-06-01

Three species of poeciliids (Gambusia holbrooki, Xiphophorus helleri and X. maculatus) and 15 species of ecologically similar native freshwater fishes (mainly eleotrids, ambassids, melanotaeniids and retropinnids) were examined for parasite richness to investigate parasite flux, qualitative differences, quantitative differences and the structuring factors in parasite communities in the 2 fish types in Queensland, Australia. Theory suggests that poeciliids would harbour depauperate parasite communities. Results supported this hypothesis; poeciliids harboured more species-poor parasite infracommunities and regional faunas than natives (P analysis of presence/absence data for poeciliids and the 6 most-sampled native fishes revealed that parasite communities of the 2 fish groups are qualitatively distinct; the proportion of parasite species with complex life-cycles was lower in poeciliids than in native species, and Myxosporea, Microspora, Coccidia and parasitic Crustacea were all absent from poeciliids. Limited exchange of parasite species has occurred between natives and poeciliids. Logistic ordinal regression analysis revealed that fish origin (exotic or native), environmental disturbance and host sex were all significant determinants of parasite community richness (P competitive advantage over native fishes because of their lack of parasites.

Transforming growth factor β inhibits platelet derived growth factor-induced vascular smooth muscle cell proliferation via Akt-independent, Smad-mediated cyclin D1 downregulation.

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Abel Martin-Garrido

Full Text Available In adult tissue, vascular smooth muscle cells (VSMCs exist in a differentiated phenotype, which is defined by the expression of contractile proteins and lack of proliferation. After vascular injury, VSMC adopt a synthetic phenotype associated with proliferation, migration and matrix secretion. The transition between phenotypes is a consequence of the extracellular environment, and in particular, is regulated by agonists such as the pro-differentiating cytokine transforming growth factor β (TGFβ and the pro-proliferative cytokine platelet derived growth factor (PDGF. In this study, we investigated the interplay between TGFβ and PDGF with respect to their ability to regulate VSMC proliferation. Stimulation of human aortic VSMC with TGFβ completely blocked proliferation induced by all isoforms of PDGF, as measured by DNA synthesis and total cell number. Mechanistically, PDGF-induced Cyclin D1 mRNA and protein expression was inhibited by TGFβ. TGFβ had no effect on PDGF activation of its receptor and ERK1/2, but inhibited Akt activation. However, constitutively active Akt did not reverse the inhibitory effect of TGFβ on Cyclin D1 expression even though inhibition of the proteasome blocked the effect of TGFβ. siRNA against Smad4 completely reversed the inhibitory effect of TGFβ on PDGF-induced Cyclin D1 expression and restored proliferation in response to PDGF. Moreover, siRNA against KLF5 prevented Cyclin D1 upregulation by PDGF and overexpression of KLF5 partially reversed TGFβ-induced inhibition of Cyclin D1 expression. Taken together, our results demonstrate that KLF5 is required for PDGF-induced Cyclin D1 expression, which is inhibited by TGFβ via a Smad dependent mechanism, resulting in arrest of VSMCs in the G1 phase of the cell cycle.

Transforming growth factor β inhibits platelet derived growth factor-induced vascular smooth muscle cell proliferation via Akt-independent, Smad-mediated cyclin D1 downregulation.

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Martin-Garrido, Abel; Williams, Holly C; Lee, Minyoung; Seidel-Rogol, Bonnie; Ci, Xinpei; Dong, Jin-Tang; Lassègue, Bernard; Martín, Alejandra San; Griendling, Kathy K

2013-01-01

In adult tissue, vascular smooth muscle cells (VSMCs) exist in a differentiated phenotype, which is defined by the expression of contractile proteins and lack of proliferation. After vascular injury, VSMC adopt a synthetic phenotype associated with proliferation, migration and matrix secretion. The transition between phenotypes is a consequence of the extracellular environment, and in particular, is regulated by agonists such as the pro-differentiating cytokine transforming growth factor β (TGFβ) and the pro-proliferative cytokine platelet derived growth factor (PDGF). In this study, we investigated the interplay between TGFβ and PDGF with respect to their ability to regulate VSMC proliferation. Stimulation of human aortic VSMC with TGFβ completely blocked proliferation induced by all isoforms of PDGF, as measured by DNA synthesis and total cell number. Mechanistically, PDGF-induced Cyclin D1 mRNA and protein expression was inhibited by TGFβ. TGFβ had no effect on PDGF activation of its receptor and ERK1/2, but inhibited Akt activation. However, constitutively active Akt did not reverse the inhibitory effect of TGFβ on Cyclin D1 expression even though inhibition of the proteasome blocked the effect of TGFβ. siRNA against Smad4 completely reversed the inhibitory effect of TGFβ on PDGF-induced Cyclin D1 expression and restored proliferation in response to PDGF. Moreover, siRNA against KLF5 prevented Cyclin D1 upregulation by PDGF and overexpression of KLF5 partially reversed TGFβ-induced inhibition of Cyclin D1 expression. Taken together, our results demonstrate that KLF5 is required for PDGF-induced Cyclin D1 expression, which is inhibited by TGFβ via a Smad dependent mechanism, resulting in arrest of VSMCs in the G1 phase of the cell cycle.

Nematode parasites of animals are more prone to develop xenobiotic resistance than nematode parasites of plants

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Silvestre A.

2004-06-01

Full Text Available In this paper, we concentrate on a comparison of plant and animal-parasitic nematodes, to gain insight into the factors that influence the acquisition of the drug resistance by nematodes. Comparing nematode parasite of domestic animals and cultivated plants, it appears that drug resistance threatens only domestic animal production. Does the paucity of report on nematicide field resistance reflect reality or, is nematicide resistance bypassed by other management practices, specific to cultivated plants (i.e. agricultural control ? First, it seems that selection pressure by treatments in plants is not as efficient as selection pressure in ruminants. Agronomic practices (i.e. sanitation, early planting, usage of nematodes resistant cultivar and crop rotation are frequently used to control parasitic-plant nematodes. Although the efficiency of such measures is generally moderate to high, integrated approaches are developing successfully in parasitic-plant nematode models. Secondly, the majority of anthelmintic resistance cases recorded in animal-parasitic nematodes concern drug families that are not used in plant-parasitic nematodes control (i.e. benzimidazoles, avermectines and levamisole. Thirdly, particular life traits of parasitic-plant nematodes (low to moderate fecundity and reproductive strategy are expected to reduce probability of appearance and transmission of drug resistance genes. It has been demonstrated that, for a large number of nematodes such as Meloidogyne spp., the mode of reproduction by mitotic parthenogenesis reduced genetic diversity of populations which may prevent a rapid drug resistance development. In conclusion, anthelmintic resistance develops in nematode parasite of animals as a consequence of an efficient selection pressure. Early detection of anthelmintic resistance is then crucial : it is not possible to avoid it, but only to delay its development in farm animal industry.

Detection of canine cytokine gene expression by reverse transcription-polymerase chain reaction.

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Pinelli, E; van der Kaaij, S Y; Slappendel, R; Fragio, C; Ruitenberg, E J; Bernadina, W; Rutten, V P

1999-08-02

Further characterization of the canine immune system will greatly benefit from the availability of tools to detect canine cytokines. Our interest concerns the study on the role of cytokines in canine visceral leishmaniasis. For this purpose, we have designed specific primers using previously published sequences for the detection of canine IL-2, IFN-gamma and IL10 mRNA by reverse transcription-polymerase chain reaction (RT-PCR). For IL-4, we have cloned and sequenced this cytokine gene, and developed canine-specific primers. To control for sample-to-sample variation in the quantity of mRNA and variation in the RT and PCR reactions, the mRNA levels of glyceraldehyde-3-phosphate dehydrogenase (G3PDH), a housekeeping gene, were determined in parallel. Primers to amplify G3PDH were designed from consensus sequences obtained from the Genbank database. The mRNA levels of the cytokines mentioned here were detected from ConA-stimulated peripheral mononuclear cells derived from Leishmania-infected dogs. A different pattern of cytokine production among infected animals was found.

The magnitude and risk factors of intestinal parasitic infection in relation to Human Immunodeficiency Virus infection and immune status, at ALERT Hospital, Addis Ababa, Ethiopia.

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Taye, Biruhalem; Desta, Kassu; Ejigu, Selamawit; Dori, Geme Urge

2014-06-01

Human Immunodeficiency Virus (HIV) and intestinal parasitic infections are among the main health problems in developing countries like Ethiopia. Particularly, co-infections of these diseases would worsen the progression of HIV to Acquired Immunodeficiency Syndrome (AIDS). The purpose of this study was to determine the magnitude and risk factors for intestinal parasites in relation to HIV infection and immune status. The study was conducted in (1) HIV positive on antiretroviral therapy (ART) and (2) ART naïve HIV positive patients, and (3) HIV-negative individuals, at All African Leprosy and Tuberculosis (TB) Eradication and Rehabilitation Training Center (ALERT) hospital in Addis Ababa, Ethiopia. Study participants were interviewed using structured questionnaires to obtain socio-demographic characteristics and assess risk factors associated with intestinal parasitic infection. Intestinal parasites were identified from fecal samples by direct wet mount, formol ether concentration, and modified Ziehl-Neelsen staining techniques. The immune status was assessed by measuring whole blood CD4 T-cell count. The overall magnitude of intestinal parasite was 35.08%. This proportion was different among study groups with 39.2% (69/176), 38.83% (40/103) and 27.14% (38/140) in ART naïve HIV positives patients, in HIV negatives, and in HIV positive on ART patients respectively. HIV positive patients on ART had significantly lower magnitude of intestinal parasitic infection compared to HIV negative individuals. Intestinal helminths were significantly lower in HIV positive on ART and ART naïve patients than HIV negatives. Low monthly income, and being married, divorced or widowed were among the socio-demographic characteristics associated with intestinal parasitic infection. No association was observed between the magnitude of intestinal parasites and CD4 T-cell count. However, Cryptosporidium parvum, and Isospora belli were exclusively identified in individuals with CD4 T

Effect of bone marrow-derived CD11b(+)F4/80 (+) immature dendritic cells on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis.

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Fu, Jingjing; Zhang, Lingling; Song, Shanshan; Sheng, Kangliang; Li, Ying; Li, Peipei; Song, Shasha; Wang, Qingtong; Chu, Jianhong; Wei, Wei

2014-05-01

To explore the effect of bone marrow-derived CD11b(+)F4/80(+) immature dendritic cells (BM CD11b(+)F4/80(+)iDC) on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis (CIA). BM CD11b(+)F4/80(+)iDC were induced with rmGM-CSF and rmIL-4, and were identified by the expressions of toll-like receptor 2 (TLR-2), indoleamine 2,3-deoxygenase (IDO), interleukin (IL)-10, transforming growth factor (TGF)-β1 and mixed leukocyte reaction (MLR). CIA was established in DBA/1 mice by immunization with type II collagen. CIA mice were injected intravenously with BM CD11b(+)F4/80(+)iDC three times after immunization. The effect of BM CD11b(+)F4/80(+)iDC on CIA was evaluated by the arthritis index, joint histopathology, body weight, thymus index, thymocytes proliferation, IL-1β, tumor necrosis factor (TNF)-α, IL-17, IL-10 and TGF-β1 levels. BM CD11b(+)F4/80(+)iDC induced with rmGM-CSF and rmIL-4 expressed high levels of TLR-2, IDO, IL-10 and TGF-β1. Infusion of BM CD11b(+)F4/80(+)iDC in CIA mice significantly reduced the arthritis index and pathological scores of joints, recovered the weight, decreased the thymus index and inhibited thymocyte proliferation. Levels of IL-1β, TNF-α and IL-17 were decreased in BM CD11b(+)F4/80(+)iDC-treated mice. BM CD11b(+)F4/80(+)iDC can be induced successfully with rmGM-CSF and rmIL-4. BM CD11b(+)F4/80(+)iDC treatment can ameliorate the development and severity of CIA by regulating the balance between pro-inflammatory cytokines and anti-inflammatory cytokines.

Immune-relevant thrombocytes of common carp undergo parasite-induced nitric oxide-mediated apoptosis.

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Fink, Inge R; Ribeiro, Carla M S; Forlenza, Maria; Taverne-Thiele, Anja; Rombout, Jan H W M; Savelkoul, Huub F J; Wiegertjes, Geert F

2015-06-01

Common carp thrombocytes account for 30-40% of peripheral blood leukocytes and are abundant in the healthy animals' spleen, the thrombopoietic organ. We show that, ex vivo, thrombocytes from healthy carp express a large number of immune-relevant genes, among which several cytokines and Toll-like receptors, clearly pointing at immune functions of carp thrombocytes. Few studies have described the role of fish thrombocytes during infection. Carp are natural host to two different but related protozoan parasites, Trypanoplasma borreli and Trypanosoma carassii, which reside in the blood and tissue fluids. We used the two parasites to undertake controlled studies on the role of fish thrombocytes during these infections. In vivo, but only during infection with T. borreli, thrombocytes were massively depleted from the blood and spleen leading to severe thrombocytopenia. Ex vivo, addition of nitric oxide induced a clear and rapid apoptosis of thrombocytes from healthy carp, supporting a role for nitric oxide-mediated control of immune-relevant thrombocytes during infection with T. borreli. The potential advantage for parasites to selectively deplete the host of thrombocytes via nitric oxide-induced apoptosis is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

INDUCTION OF CYTOKINE PRODUCTION IN CHEETAH (ACINONYX JUBATUS) PERIPHERAL BLOOD MONONUCLEAR CELLS AND VALIDATION OF FELINE-SPECIFIC CYTOKINE ASSAYS FOR ANALYSIS OF CHEETAH SERUM.

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Franklin, Ashley D; Crosier, Adrienne E; Vansandt, Lindsey M; Mattson, Elliot; Xiao, Zhengguo

2015-06-01

Peripheral blood mononuclear cells (PBMCs) were isolated from the whole blood of cheetahs (Acinonyx jubatus ; n=3) and stimulated with lipopolysaccharides (LPS) to induce the production of proinflammatory cytokines TNF-α, IL-1β, and IL-6 for establishment of cross-reactivity between these cheetah cytokines and feline-specific cytokine antibodies provided in commercially available Feline DuoSet® ELISA kits (R&D Systems, Inc., Minneapolis, Minnesota 55413, USA). This study found that feline-specific cytokine antibodies bind specifically to cheetah proinflammatory cytokines TNF-α, IL-1β, and IL-6 from cell culture supernatants. The assays also revealed that cheetah PBMCs produce a measurable, cell concentration-dependent increase in proinflammatory cytokine production after LPS stimulation. To enable the use of these kits, which are designed for cell culture supernatants for analyzing cytokine concentrations in cheetah serum, percent recovery and parallelism of feline cytokine standards in cheetah serum were also evaluated. Cytokine concentrations in cheetah serum were approximated based on the use of domestic cat standards in the absence of cheetah standard material. In all cases (for cytokines TNF-α, IL-1β, and IL-6), percent recovery increased as the serum sample dilution increased, though percent recovery varied between cytokines at a given dilution factor. A 1:2 dilution of serum resulted in approximately 45, 82, and 7% recovery of TNF-α, IL-1β, and IL-6 standards, respectively. Adequate parallelism was observed across a large range of cytokine concentrations for TNF-α and IL-1β; however, a significant departure from parallelism was observed between the IL-6 standard and the serum samples (P=0.004). Therefore, based on our results, the Feline DuoSet ELISA (R&D Systems, Inc.) kits are valid assays for the measurement of TNF-α and IL-1β in cheetah serum but should not be used for accurate measurement of IL-6.

Efficacy of Selenium Supplement on Gene Expression of Inflammatory Cytokines and Vascular Endothelial Growth Factor in Gestational Diabetes

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Mehri Jamilian

2018-01-01

Full Text Available Abstract Background: Selenium supplement has multiple important effects, including anti-inflammatory effect. The aim of this study was to assess the effects of selenium supplement on gene expression of inflammatory cytokines and vascular endothelial growth factor in gestational diabetes. Materials and Methods: This randomized double blind placebo control trial was performed on 40 patients suffering from GDM aged 18–40 years old. Participants were randomly divided into interventional group receiving 200mg/day selenium supplements (n=20 and control group receiving placebo (n=20 for 6 weeks. Primary outcome was gene expression of inflammatory cytokines and VEGF which were assessed in lymphocyte of GDM patients by RT-PCR method. Results: After 6 weeks intervention, in comparison with the control group, interventional group showed down regulation of gene expression of tumor necrosis factor alpha (TNF–α (p=0.02 and transforming growth factor beta (TGF–β (p=0.01 and up-regulation of gene expression of vascular endothelial (VEGF (p = 0.03 in lymphocytes of GDM. There was not any significant change following intervention with selenium regarding gene expression of interleukin IL-1 β and IL-8 in lymphocytes of GDM patients. Conclusion: 6 weeks supplementation with selenium in patients with GDM can cause down regulated gene expression of TNF-α and TGF–β, and up regulated gene expression of VEGF. Selenium supplement had not any effect on gene expression of IL-1 β and IL-8.

Plasma cytokine expression in adolescent chronic fatigue syndrome.

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Wyller, Vegard Bruun; Sørensen, Øystein; Sulheim, Dag; Fagermoen, Even; Ueland, Thor; Mollnes, Tom Eirik

2015-05-01

Chronic fatigue syndrome (CFS) is a prevalent and disabling condition among adolescents. The pathophysiology is poorly understood, but low-grade systemic inflammation has been suggested as an important component. This study compared circulating levels of individual cytokines and parameters of cytokine networks in a large set of adolescent CFS patients and healthy controls, and explored associations between cytokines and symptoms in the CFS group. CFS patients (12-18years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case definition of CFS was applied, requiring three months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Thus, the case definition was broader than the Fukuda-criteria of CFS. Healthy controls having comparable distribution of gender and age were recruited from local schools. Twenty-seven plasma cytokines, including interleukins, chemokines and growth factors were assayed using multiplex technology. The results were subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and patients were subgrouped according to the Fukuda-criteria. A total of 120 CFS patients and 68 healthy controls were included. CFS patients had higher scores for fatigue (p<0.001) and inflammatory symptoms (p<0.001) than healthy controls. All cytokine levels and cytokine network parameters were similar, and none of the differences were statistically different across the two groups, also when adjusting for adherence to the Fukuda criteria of CFS. Within the CFS group, there were no associations between aggregate cytokine network parameters and symptom scores. Adolescent CFS patients are burdened by symptoms that might suggest low-grade systemic inflammation, but plasma levels of individual cytokines as well as cytokine network measures were not different from healthy controls, and

Developmental and Functional Control of Natural Killer Cells by Cytokines

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Yang Wu

2017-08-01

Full Text Available Natural killer (NK cells are effective in combating infections and tumors and as such are tempting for adoptive transfer therapy. However, they are not homogeneous but can be divided into three main subsets, including cytotoxic, tolerant, and regulatory NK cells, with disparate phenotypes and functions in diverse tissues. The development and functions of such NK cells are controlled by various cytokines, such as fms-like tyrosine kinase 3 ligand (FL, kit ligand (KL, interleukin (IL-3, IL-10, IL-12, IL-18, transforming growth factor-β, and common-γ chain family cytokines, which operate at different stages by regulating distinct signaling pathways. Nevertheless, the specific roles of each cytokine that regulates NK cell development or that shapes different NK cell functions remain unclear. In this review, we attempt to describe the characteristics of each cytokine and the existing protocols to expand NK cells using different combinations of cytokines and feeder cells. A comprehensive understanding of the role of cytokines in NK cell development and function will aid the generation of better efficacy for adoptive NK cell treatment.

The ecology of parasites of freshwater fishes: the search for patterns.

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Kennedy, C R

2009-10-01

Developments in the study of the ecology of helminth parasites of freshwater fishes over the last half century are reviewed. Most research has of necessity been field based and has involved the search for patterns in population and community dynamics that are repeatable in space and time. Mathematical models predict that under certain conditions host and parasite populations can attain equilibrial levels through operation of regulatory factors. Such factors have been identified in several host-parasite systems and some parasite populations have been shown to persist over long time-periods. However, there is no convincing evidence that fish parasite populations are stable and regulated since in all cases alternative explanations are equally acceptable and it appears that they are non-equilibrial systems. It has proved particularly difficult to detect replicable patterns in parasite communities. Inter-specific competition, evidenced by functional and numerical responses, has been detected in several communities but its occurrence is erratic and its significance unclear. Some studies have failed to find any nested patterns in parasite community structure and richness, whereas others have identified such patterns although they are seldom constant over space and time. Departures from randomness appear to be the exception and then only temporary. It appears that parasite communities are non-equilibrial, stochastic assemblages rather than structured and organized.

Cytokine Secreting Microparticles Engineer the Fate and the Effector Functions of T-Cells.

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Majedi, Fatemeh S; Hasani-Sadrabadi, Mohammad Mahdi; Kidani, Yoko; Thauland, Timothy J; Moshaverinia, Alireza; Butte, Manish J; Bensinger, Steven J; Bouchard, Louis-S

2018-02-01

T-cell immunotherapy is a promising approach for cancer, infection, and autoimmune diseases. However, significant challenges hamper its therapeutic potential, including insufficient activation, delivery, and clonal expansion of T-cells into the tumor environment. To facilitate T-cell activation and differentiation in vitro, core-shell microparticles are developed for sustained delivery of cytokines. These particles are enriched by heparin to enable a steady release of interleukin-2 (IL-2), the major T-cell growth factor, over 10+ d. The controlled delivery of cytokines is used to steer lineage specification of cultured T-cells. This approach enables differentiation of T-cells into central memory and effector memory subsets. It is shown that the sustained release of stromal cell-derived factor 1α could accelerate T-cell migration. It is demonstrated that CD4+ T-cells could be induced to high concentrations of regulatory T-cells through controlled release of IL-2 and transforming growth factor beta. It is found that CD8+ T-cells that received IL-2 from microparticles are more likely to gain effector functions as compared with traditional administration of IL-2. Culture of T-cells within 3D scaffolds that contain IL-2-secreting microparticles enhances proliferation as compared with traditional, 2D approaches. This yield a new method to control the fate of T-cells and ultimately to new strategies for immune therapy. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Investigation of Antileishmanial Activities of Acridines Derivatives against Promastigotes and Amastigotes Form of Parasites Using Quantitative Structure Activity Relationship Analysis

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Samir Chtita

2016-01-01

Full Text Available In a search of newer and potent antileishmanial (against promastigotes and amastigotes form of parasites drug, a series of 60 variously substituted acridines derivatives were subjected to a quantitative structure activity relationship (QSAR analysis for studying, interpreting, and predicting activities and designing new compounds by using multiple linear regression and artificial neural network (ANN methods. The used descriptors were computed with Gaussian 03, ACD/ChemSketch, Marvin Sketch, and ChemOffice programs. The QSAR models developed were validated according to the principles set up by the Organisation for Economic Co-operation and Development (OECD. The principal component analysis (PCA has been used to select descriptors that show a high correlation with activities. The univariate partitioning (UP method was used to divide the dataset into training and test sets. The multiple linear regression (MLR method showed a correlation coefficient of 0.850 and 0.814 for antileishmanial activities against promastigotes and amastigotes forms of parasites, respectively. Internal and external validations were used to determine the statistical quality of QSAR of the two MLR models. The artificial neural network (ANN method, considering the relevant descriptors obtained from the MLR, showed a correlation coefficient of 0.933 and 0.918 with 7-3-1 and 6-3-1 ANN models architecture for antileishmanial activities against promastigotes and amastigotes forms of parasites, respectively. The applicability domain of MLR models was investigated using simple and leverage approaches to detect outliers and outsides compounds. The effects of different descriptors in the activities were described and used to study and design new compounds with higher activities compared to the existing ones.

Determinants of serum brain-derived neurotrophic factor

NARCIS (Netherlands)

Bus, B. A. A.; Molendijk, M. L.; Penninx, B. J. W. H.; Buitelaar, J. K.; Kenis, G.; Prickaerts, J.; Elzinga, B. M.; Voshaar, R. C. Oude

Background: Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of growth factors and affects the survival and plasticity of neurons in the adult central nervous system. The high correlation between cortical and serum BDNF levels has led to many human studies on BDNF levels

Bone-marrow-derived mesenchymal stem cells inhibit gastric aspiration lung injury and inflammation in rats.

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Zhou, Jing; Jiang, Liyan; Long, Xuan; Fu, Cuiping; Wang, Xiangdong; Wu, Xiaodan; Liu, Zilong; Zhu, Fen; Shi, Jindong; Li, Shanqun

2016-09-01

Gastric aspiration lung injury is one of the most common clinical events. This study investigated the effects of bone-marrow-derived mesenchymal stem cells (BMSCs) on combined acid plus small non-acidified particle (CASP)-induced aspiration lung injury. Enhanced green fluorescent protein (EGFP(+) ) or EGFP(-) BMSCs or 15d-PGJ2 were injected via the tail vein into rats immediately after CASP-induced aspiration lung injury. Pathological changes in lung tissues, blood gas analysis, the wet/dry weight ratio (W/D) of the lung, levels of total proteins and number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) were determined. The cytokine levels were measured using ELISA. Protein expression was determined by Western blot. Bone-marrow-derived mesenchymal stem cells treatment significantly reduced alveolar oedema, exudation and lung inflammation; increased the arterial partial pressure of oxygen; and decreased the W/D of the lung, the levels of total proteins and the number of total cells and neutrophils in BALF in the rats with CASP-induced lung injury. Bone-marrow-derived mesenchymal stem cells treatment decreased the levels of tumour necrosis factor-α and Cytokine-induced neutrophil chemoattractant (CINC)-1 and the expression of p-p65 and increased the levels of interleukin-10 and 15d-PGJ2 and the expression of peroxisome proliferator-activated receptor (PPAR)-γ in the lung tissue in CASP-induced rats. Tumour necrosis factor-α stimulated BMSCs to secrete 15d-PGJ2 . A tracking experiment showed that EGFP(+) BMSCs were able to migrate to local lung tissues. Treatment with 15d-PGJ2 also significantly inhibited CASP-induced lung inflammation and the production of pro-inflammatory cytokines. Our results show that BMSCs can protect lung tissues from gastric aspiration injury and inhibit lung inflammation in rats. A beneficial effect might be achieved through BMSC-derived 15d-PGJ2 activation of the PPAR-γ receptor, reducing the production of

Bovine immunity - a driver for diversity in Theileria parasites?

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McKeever, Declan J

2009-06-01

Theileria parva and Theileria annulata are tick-borne parasites of cattle that infect and transform leukocytes, causing severe and often fatal parasitic leukoses. Both species provoke strong immunity against subsequent infection. However, considerable diversity is observed in field populations of each parasite and protection is only assured against homologous challenge. The life cycles of these parasites are complex and involve prolonged exposure to host and vector defence mechanisms. Although the relevant vector mechanisms are poorly defined, protective responses of cattle seem to be tightly focused and variable in their specificity between individuals. This review considers whether bovine immunity acts as a driver for diversity in T. parva and T. annulata and explores other factors that might underlie genetic variation in these parasites.

Parasites in the Wadden Sea food web

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Thieltges, David W.; Engelsma, Marc Y.; Wendling, Carolin C.; Wegner, K. Mathias

2013-09-01

While the free-living fauna of the Wadden Sea has received much interest, little is known on the distribution and effects of parasites in the Wadden Sea food web. However, recent studies on this special type of trophic interaction indicate a high diversity of parasites in the Wadden Sea and suggest a multitude of effects on the hosts. This also includes effects on specific predator-prey relationships and the general structure of the food web. Focussing on molluscs, a major group in the Wadden Sea in terms of biomass and abundance and an important link between primary producers and predators, we review existing studies and exemplify the ecological role of parasites in the Wadden Sea food web. First, we give a brief inventory of parasites occurring in the Wadden Sea, ranging from microparasites (e.g. protozoa, bacteria) to macroparasites (e.g. helminths, parasitic copepods) and discuss the effects of spatial scale on heterogeneities in infection levels. We then demonstrate how parasites can affect host population dynamics by acting as a strong mortality factor, causing mollusc mass mortalities. In addition, we will exemplify how parasites can mediate the interaction strength of predator-prey relationships and affect the topological structure of the Wadden Sea food web as a whole. Finally, we highlight some ongoing changes regarding parasitism in the Wadden Sea in the course of global change (e.g. species introduction, climate change) and identify important future research questions to entangle the role of parasites in the Wadden Sea food web.

Expression of interleukin-15 and inflammatory cytokines in skeletal muscles of STZ-induced diabetic rats: effect of resistance exercise training.

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Molanouri Shamsi, M; Hassan, Z H; Gharakhanlou, R; Quinn, L S; Azadmanesh, K; Baghersad, L; Isanejad, A; Mahdavi, M

2014-05-01

Skeletal muscle atrophy is associated with type-1 diabetes. Skeletal muscle is the source of pro- and anti-inflammatory cytokines that can mediate muscle hypertrophy and atrophy, while resistance exercise can modulate both muscle mass and muscle cytokine expression. This study determined the effects of a 5-week resistance exercise training regimen on the expression of muscle cytokines in healthy and streptozotocin-induced diabetic rats, with special emphasis on interleukin-15 (IL-15), a muscle-derived cytokine proposed to be involved in muscle hypertrophy or responses to stress. Induction of diabetes reduced muscle weight in both the fast flexor hallucis longus (FHL) and slow soleus muscles, while resistance training preserved FHL muscle weight in diabetic rats. IL-15 protein content was increased by training in both FHL and soleus muscles, as well as serum, in normal and diabetic rats. With regard to proinflammatory cytokines, muscle IL-6 levels were increased in diabetic rats, while training decreased muscle IL-6 levels in diabetic rats; training had no effect on FHL muscle IL-6 levels in healthy rats. Also, tumor necrosis factor-alpha (TNF-α) and IL-1β levels were increased by diabetes, but not changed by training. In conclusion, we found that in diabetic rats, resistance training increased muscle and serum IL-15 levels, decreased muscle IL-6 levels, and preserved FHL muscle mass.

Helminth parasites of conventionally mantained laboratory mice

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Roberto Magalhães Pinto

1994-03-01

Full Text Available The spectrum of intestinal parasites present in the SwissWebster, C57B1/6 and DBA/2 mice strains from different animal houses was identified and prevalences compared. Three parasites were observed during the course ofthis study, namely the cestode. Vampirolepis nana (Siebold, 1852 Spasskii, 1954(=Hymenolepis nana and the nematodes Aspiculuris tetraptera (Nitzsch, 1821 Schulz, 1924 and Syphacia obvelata (Rudolphi, 1802 Seurat, 1916. The scope of thisinvestigation has been widened to also include morphometric data on the parasites, to further simplify their identification, since the presence of helminths in laboratory animals is regarded as a restricting factor for the proper attainment of experimental protocols.

Cytokine and chemokine levels in tears from healthy subjects.

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Carreño, Ester; Enríquez-de-Salamanca, Amalia; Tesón, Marisa; García-Vázquez, Carmen; Stern, Michael E; Whitcup, Scott M; Calonge, Margarita

2010-11-01

There is growing evidence for the existence of an 'immune tone' in normal tears. The aim of this study was to determine the levels of a large panel of cytokines and chemokines in tears obtained from healthy subjects. These levels can then serve as baseline values for comparison with patients suffering from ocular surface diseases. Nine healthy subjects participated in this study, and normal ocular surface health was documented by the results of a dry eye questionnaire, Schirmer strip wetting, and vital staining of the cornea. Four microliters of tears were collected from each eye and analysed separately with multiplex bead-based assays for the concentration of 30 cytokines and chemokines. Twenty-five cytokines/chemokines were detected. CCL11/Eotaxin1, GM-CSF, G-CSF, IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-10, IL-13, IL-12p70, IL-15, CX3CL1/Fractalkine, TNF-α, epidermal growth factor, and CCL4/MIP-1β were present at 5-100 pg/ml. IL-1β, IL-6, IL-7A, CXCL8/IL-8, and CCL2/MCP-1 were present at 100-400 pg/ml. IL-1Ra, CXCL10/IP-10 and vascular endothelial growth factor were present at more than 1000 pg/ml. Multiplex bead-based assays are convenient for cytokine/chemokine detection in tears. Fracktalkine has been detected in human healthy tears for the first time. The knowledge of cytokine/chemokine concentrations in tears from normal subjects is an important reference for further comparison with patients suffering from ocular surface diseases. Variability in their levels can reflect a phenomenon of potential importance for the understanding of the ocular surface cytokine pattern. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

Found in Translation: Applying Lessons from Model Systems to Strigolactone Signaling in Parasitic Plants.

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Lumba, Shelley; Subha, Asrinus; McCourt, Peter

2017-07-01

Strigolactones (SLs) are small molecules that act as endogenous hormones to regulate plant development as well as exogenous cues that help parasitic plants to infect their hosts. Given that parasitic plants are experimentally challenging systems, researchers are using two approaches to understand how they respond to host-derived SLs. The first involves extrapolating information on SLs from model genetic systems to dissect their roles in parasitic plants. The second uses chemicals to probe SL signaling directly in the parasite Striga hermonthica. These approaches indicate that parasitic plants have co-opted a family of α/β hydrolases to perceive SLs. The importance of this genetic and chemical information cannot be overstated since parasitic plant infestations are major obstacles to food security in the developing world. Copyright © 2017 Elsevier Ltd. All rights reserved.

Global issues in allergy and immunology: Parasitic infections and allergy.

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Cruz, Alvaro A; Cooper, Philip J; Figueiredo, Camila A; Alcantara-Neves, Neuza M; Rodrigues, Laura C; Barreto, Mauricio L

2017-11-01

Allergic diseases are on the increase globally in parallel with a decrease in parasitic infection. The inverse association between parasitic infections and allergy at an ecological level suggests a causal association. Studies in human subjects have generated a large knowledge base on the complexity of the interrelationship between parasitic infection and allergy. There is evidence for causal links, but the data from animal models are the most compelling: despite the strong type 2 immune responses they induce, helminth infections can suppress allergy through regulatory pathways. Conversely, many helminths can cause allergic-type inflammation, including symptoms of "classical" allergic disease. From an evolutionary perspective, subjects with an effective immune response against helminths can be more susceptible to allergy. This narrative review aims to inform readers of the most relevant up-to-date evidence on the relationship between parasites and allergy. Experiments in animal models have demonstrated the potential benefits of helminth infection or administration of helminth-derived molecules on chronic inflammatory diseases, but thus far, clinical trials in human subjects have not demonstrated unequivocal clinical benefits. Nevertheless, there is sufficiently strong evidence to support continued investigation of the potential benefits of helminth-derived therapies for the prevention or treatment of allergic and other inflammatory diseases. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Evaluation of amniotic mesenchymal cell derivatives on cytokine production in equine alveolar macrophages: an in vitro approach to lung inflammation.

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Zucca, Enrica; Corsini, Emanuela; Galbiati, Valentina; Lange-Consiglio, Anna; Ferrucci, Francesco

2016-09-20

Data obtained in both animal models and clinical trials suggest that cell-based therapies represent a potential therapeutic strategy for lung repair and remodeling. Recently, new therapeutic approaches based on the use of stem cell derivatives (e.g., conditioned medium (CM) and microvesicles (MVs)) to regenerate tissues and improve their functions were proposed. The aim of this study was to investigate the immunomodulatory effects of equine amniotic mesenchymal cell derivatives on lipopolysaccharide (LPS)-induced cytokine production in equine alveolar macrophages, which may be beneficial in lung inflammatory disorders such as recurrent airway obstruction (RAO) in horses. RAO shares many features with human asthma, including an increased number of cells expressing mRNA for interleukin (IL)-4 and IL-5 and a decreased expression of IFN-γ in bronchoalveolar lavage fluid (BALF) of affected horses. The release of TNF-α, IL-6, and TGF-β1 at different time points (1, 24, 48, and 72 h) was measured in equine alveolar macrophages stimulated or not with LPS (10 and 100 ng/mL) in the presence or absence of 10 % CM or 50 × 10(6) MVs/mL. Cytokines were measured using commercially available ELISA kits. For multiple comparisons, analysis of variance was used with Tukey post-hoc test. Differences were considered significant at p ≤ 0.05. Significant modulatory effects of CM on LPS-induced TNF-α release at 24 h, and of both CM and MVs on TNF-α release at 48 h were observed. A trend toward a modulatory effect of both CM and MVs on the release of TGF-β and possibly IL-6 was visible over time. Results support the potential use of CM and MVs in lung regenerative medicine, especially in situations in which TGF-β may be detrimental, such as respiratory allergy. Further studies should evaluate the potential clinical applications of CM and MVs in equine lung diseases, such as RAO and other inflammatory disorders.

Forced expression of stabilized c-Fos in dendritic cells reduces cytokine production and immune responses in vivo

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Yoshida, Ryoko; Suzuki, Mayu; Sakaguchi, Ryota; Hasegawa, Eiichi; Kimura, Akihiro; Shichita, Takashi; Sekiya, Takashi [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582 (Japan); Japan Science and Technology Agency, CREST, Chiyoda-ku 102-0075 (Japan); Shiraishi, Hiroshi [Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga (Japan); Shimoda, Kouji [Department of Laboratory Animal Center, Keio University School of Medicine, Tokyo (Japan); Yoshimura, Akihiko, E-mail: yoshimura@a6.keio.jp [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582 (Japan); Japan Science and Technology Agency, CREST, Chiyoda-ku 102-0075 (Japan)

2012-06-29

Highlights: Black-Right-Pointing-Pointer Dendritic cells expressing stabilized c-Fos produced less inflammatory cytokines. Black-Right-Pointing-Pointer Dendritic cells expressing stabilized c-Fos activated T cells less efficiently. Black-Right-Pointing-Pointer Transgenic mice expressing stabilized c-Fos were resistant to EAE model. -- Abstract: Intracellular cyclic adenosine monophosphate (cAMP) suppresses innate immunity by inhibiting proinflammatory cytokine production by monocytic cells. We have shown that the transcription factor c-Fos is responsible for cAMP-mediated suppression of inflammatory cytokine production, and that c-Fos protein is stabilized by IKK{beta}-mediated phosphorylation. We found that S308 is one of the major phosphorylation sites, and that the S308D mutation prolongs c-Fos halflife. To investigate the role of stabilized c-Fos protein in dendritic cells (DCs) in vivo, we generated CD11c-promoter-deriven c-FosS308D transgenic mice. As expected, bone marrow-derived DCs (BMDCs) from these Tg mice produced smaller amounts of inflammatory cytokines, including TNF-{alpha}, IL-12, and IL-23, but higher levels of IL-10, in response to LPS, than those from wild-type (Wt) mice. When T cells were co-cultured with BMDCs from Tg mice, production of Th1 and Th17 cytokines was reduced, although T cell proliferation was not affected. Tg mice demonstrated more resistance to experimental autoimmune encephalomyelitis (EAE) than did Wt mice. These data suggest that c-Fos in DCs plays a suppressive role in certain innate and adaptive immune responses.

Proinflammatory cytokine levels in patients with conversion disorder.

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Tiyekli, Utkan; Calıyurt, Okan; Tiyekli, Nimet Dilek

2013-06-01

It was aimed to evaluate the relationship between proinflammatory cytokine levels and conversion disorder both commonly known as stress regulated. Baseline proinflammatory cytokine levels-[Tumour necrosis factor alpha (TNF-α), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6)]-were evaluated with enzyme-linked immunosorbent assay in 35 conversion disorder patients and 30 healthy controls. Possible changes in proinflammatory cytokine levels were evaluated again, after their acute phase in conversion disorder patients. Statistically significant decreased serum TNF-α levels were obtained in acute phase of conversion disorder. Those levels increased after acute conversion phase. There were no statistically significant difference observed between groups in serum IL-1β and (IL-6) levels. Stress associated with conversion disorder may suppress immune function in acute conversion phase and may have diagnostic and therapeutic value.

Idiosyncratic Drug-Induced Liver Injury: Is Drug-Cytokine Interaction the Linchpin?

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Roth, Robert A; Maiuri, Ashley R; Ganey, Patricia E

2017-02-01

Idiosyncratic drug-induced liver injury continues to be a human health problem in part because drugs that cause these reactions are not identified in current preclinical testing and because progress in prevention is hampered by incomplete knowledge of mechanisms that underlie these adverse responses. Several hypotheses involving adaptive immune responses, inflammatory stress, inability to adapt to stress, and multiple, concurrent factors have been proposed. Yet much remains unknown about how drugs interact with the liver to effect death of hepatocytes. Evidence supporting hypotheses implicating adaptive or innate immune responses in afflicted patients has begun to emerge and is bolstered by results obtained in experimental animal models and in vitro systems. A commonality in adaptive and innate immunity is the production of cytokines, including interferon-γ (IFNγ). IFNγ initiates cell signaling pathways that culminate in cell death or inhibition of proliferative repair. Tumor necrosis factor-α, another cytokine prominent in immune responses, can also promote cell death. Furthermore, tumor necrosis factor-α interacts with IFNγ, leading to enhanced cellular responses to each cytokine. In this short review, we propose that the interaction of drugs with these cytokines contributes to idiosyncratic drug-induced liver injury, and mechanisms by which this could occur are discussed. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Density-dependence and within-host competition in a semelparous parasite of leaf-cutting ants

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Thomsen Lene

2004-11-01

Full Text Available Abstract Background Parasite heterogeneity and within-host competition are thought to be important factors influencing the dynamics of host-parasite relationships. Yet, while there have been many theoretical investigations of how these factors may act, empirical data is more limited. We investigated the effects of parasite density and heterogeneity on parasite virulence and fitness using four strains of the entomopathogenic fungus, Metarhizium anisopliae var. anisopliae, and its leaf-cutting ant host Acromyrmex echinatior as the model system. Results The relationship between parasite density and infection was sigmoidal, with there being an invasion threshold for an infection to occur (an Allee effect. Although spore production was positively density-dependent, parasite fitness decreased with increasing parasite density, indicating within-host scramble competition. The dynamics differed little between the four strains tested. In mixed infections of three strains the infection-growth dynamics were unaffected by parasite heterogeneity. Conclusions The strength of within-host competition makes dispersal the best strategy for the parasite. Parasite heterogeneity may not have effected virulence or the infection dynamics either because the most virulent strain outcompeted the others, or because the interaction involved scramble competition that was impervious to parasite heterogeneity. The dynamics observed may be common for virulent parasites, such as Metarhizium, that produce aggregated transmission stages. Such parasites make useful models for investigating infection dynamics and the impact of parasite competition.

Anthropogenics: human influence on global and genetic homogenization of parasite populations.

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Zarlenga, Dante S; Hoberg, Eric; Rosenthal, Benjamin; Mattiucci, Simonetta; Nascetti, Giuseppe

2014-12-01

The distribution, abundance, and diversity of life on Earth have been greatly shaped by human activities. This includes the geographic expansion of parasites; however, measuring the extent to which humans have influenced the dissemination and population structure of parasites has been challenging. In-depth comparisons among parasite populations extending to landscape-level processes affecting disease emergence have remained elusive. New research methods have enhanced our capacity to discern human impact, where the tools of population genetics and molecular epidemiology have begun to shed light on our historical and ongoing influence. Only since the 1990s have parasitologists coupled morphological diagnosis, long considered the basis of surveillance and biodiversity studies, with state-of-the-art tools enabling variation to be examined among, and within, parasite populations. Prior to this time, populations were characterized only by phenotypic attributes such as virulence, infectivity, host range, and geographical location. The advent of genetic/molecular methodologies (multilocus allozyme electrophoresis, polymerase chain reaction-DNA [PCR-DNA] fragments analysis, DNA sequencing, DNA microsatellites, single nucleotide polymorphisms, etc.) have transformed our abilities to reveal variation among, and within, populations at local, regional, landscape, and global scales, and thereby enhanced our understanding of the biosphere. Numerous factors can affect population structure among parasites, e.g., evolutionary and ecological history, mode of reproduction and transmission, host dispersal, and life-cycle complexity. Although such influences can vary considerably among parasite taxa, anthropogenic factors are demonstrably perturbing parasite fauna. Minimal genetic structure among many geographically distinct (isolated) populations is a hallmark of human activity, hastened by geographic introductions, environmental perturbation, and global warming. Accelerating

Dioctophyme renale: prevalence and risk factors of parasitism in dogs of São Cristóvão district, Três Barras county, Santa Catarina State, Brazil

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Daniela Pedrassani

Full Text Available Abstract Dioctophyme renale is a nematode that can be found parasitizing the kidney, peritoneal cavity and, rarely, other organs of canids and mustelids. This disease has high occurrence in the municipality of Três Barras, state of Santa Catarina, thus making this an interesting area to study the epidemiological aspects of infection by D. renale in dogs. Among 197 dogs, 14.2% showed the parasite eggs in urine and 16.4% showed IgG antibodies anti-D. renale in serum samples according to the indirect ELISA method; among seropositive dogs, 15 (37.5% animals did not show any parasite eggs in their urine. Parasitism was more frequent in females, and there was no finding of interference from age on parasitism. Factors such as water potential and presence of paratenic hosts in the studied region were reported by the owners of dogs and may have contributed to the occurrence of parasitism.

Inhibition of early T cell cytokine production by arsenic trioxide occurs independently of Nrf2.

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Kelly R VanDenBerg

Full Text Available Nuclear factor erythroid 2-related factor 2 (Nrf2 is a stress-activated transcription factor that induces a variety of cytoprotective genes. Nrf2 also mediates immunosuppressive effects in multiple inflammatory models. Upon activation, Nrf2 dissociates from its repressor protein, Keap1, and translocates to the nucleus where it induces Nrf2 target genes. The Nrf2-Keap1 interaction is disrupted by the environmental toxicant and chemotherapeutic agent arsenic trioxide (ATO. The purpose of the present study was to determine the effects of ATO on early events of T cell activation and the role of Nrf2 in those effects. The Nrf2 target genes Hmox-1, Nqo-1, and Gclc were all upregulated by ATO (1-2 μM in splenocytes derived from wild-type, but not Nrf2-null, mice, suggesting that Nrf2 is activated by ATO in splenocytes. ATO also inhibited IFNγ, IL-2, and GM-CSF mRNA and protein production in wild-type splenocytes activated with the T cell activator, anti-CD3/anti-CD28. However, ATO also decreased production of these cytokines in activated splenocytes from Nrf2-null mice, suggesting the inhibition is independent of Nrf2. Interestingly, ATO inhibited TNFα protein secretion, but not mRNA expression, in activated splenocytes suggesting the inhibition is due to post-transcriptional modification. In addition, c-Fos DNA binding was significantly diminished by ATO in wild-type and Nrf2-null splenocytes activated with anti-CD3/anti-CD28, consistent with the observed inhibition of cytokine production by ATO. Collectively, this study suggests that although ATO activates Nrf2 in splenocytes, inhibition of early T cell cytokine production by ATO occurs independently of Nrf2 and may instead be due to impaired AP-1 DNA binding.