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Sample records for cells modulates inflammation

  1. Aryl Hydrocarbon Receptor Protects Lungs from Cockroach Allergen-Induced Inflammation by Modulating Mesenchymal Stem Cells.

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    Xu, Ting; Zhou, Yufeng; Qiu, Lipeng; Do, Danh C; Zhao, Yilin; Cui, Zhuang; Wang, Heng; Liu, Xiaopeng; Saradna, Arjun; Cao, Xu; Wan, Mei; Gao, Peisong

    2015-12-15

    Exposure to cockroach allergen leads to allergic sensitization and increased risk of developing asthma. Aryl hydrocarbon receptor (AhR), a receptor for many common environmental contaminants, can sense not only environmental pollutants but also microbial insults. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to modulate immune responses. In this study, we investigated whether AhR can sense cockroach allergens and modulate allergen-induced lung inflammation through MSCs. We found that cockroach allergen-treated AhR-deficient (AhR(-/-)) mice showed exacerbation of lung inflammation when compared with wild-type (WT) mice. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an AhR agonist, significantly suppressed allergen-induced mouse lung inflammation. MSCs were significantly reduced in cockroach allergen-challenged AhR(-/-) mice as compared with WT mice, but increased in cockroach allergen-challenged WT mice when treated with TCDD. Moreover, MSCs express AhR, and AhR signaling can be activated by cockroach allergen with increased expression of its downstream genes cyp1a1 and cyp1b1. Furthermore, we tracked the migration of i.v.-injected GFP(+) MSCs and found that cockroach allergen-challenged AhR(-/-) mice displayed less migration of MSCs to the lungs compared with WT. The AhR-mediated MSC migration was further verified by an in vitro Transwell migration assay. Epithelial conditioned medium prepared from cockroach extract-challenged epithelial cells significantly induced MSC migration, which was further enhanced by TCDD. The administration of MSCs significantly attenuated cockroach allergen-induced inflammation, which was abolished by TGF-β1-neutralizing Ab. These results suggest that AhR plays an important role in protecting lungs from allergen-induced inflammation by modulating MSC recruitment and their immune-suppressive activity. PMID:26561548

  2. Cell walls of Saccharomyces cerevisiae differentially modulated innate immunity and glucose metabolism during late systemic inflammation.

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    Bushansingh Baurhoo

    Full Text Available BACKGROUND: Salmonella causes acute systemic inflammation by using its virulence factors to invade the intestinal epithelium. But, prolonged inflammation may provoke severe body catabolism and immunological diseases. Salmonella has become more life-threatening due to emergence of multiple-antibiotic resistant strains. Mannose-rich oligosaccharides (MOS from cells walls of Saccharomyces cerevisiae have shown to bind mannose-specific lectin of Gram-negative bacteria including Salmonella, and prevent their adherence to intestinal epithelial cells. However, whether MOS may potentially mitigate systemic inflammation is not investigated yet. Moreover, molecular events underlying innate immune responses and metabolic activities during late inflammation, in presence or absence of MOS, are unknown. METHODS AND PRINCIPAL FINDINGS: Using a Salmonella LPS-induced systemic inflammation chicken model and microarray analysis, we investigated the effects of MOS and virginiamycin (VIRG, a sub-therapeutic antibiotic on innate immunity and glucose metabolism during late inflammation. Here, we demonstrate that MOS and VIRG modulated innate immunity and metabolic genes differently. Innate immune responses were principally mediated by intestinal IL-3, but not TNF-α, IL-1 or IL-6, whereas glucose mobilization occurred through intestinal gluconeogenesis only. MOS inherently induced IL-3 expression in control hosts. Consequent to LPS challenge, IL-3 induction in VIRG hosts but not differentially expressed in MOS hosts revealed that MOS counteracted LPS's detrimental inflammatory effects. Metabolic pathways are built to elucidate the mechanisms by which VIRG host's higher energy requirements were met: including gene up-regulations for intestinal gluconeogenesis (PEPCK and liver glycolysis (ENO2, and intriguingly liver fatty acid synthesis through ATP citrate synthase (CS down-regulation and ATP citrate lyase (ACLY and malic enzyme (ME up-regulations. However, MOS host

  3. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells.

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    Verinaud, Liana; Lopes, Stefanie Costa Pinto; Prado, Isabel Cristina Naranjo; Zanucoli, Fábio; Alves da Costa, Thiago; Di Gangi, Rosária; Issayama, Luidy Kazuo; Carvalho, Ana Carolina; Bonfanti, Amanda Pires; Niederauer, Guilherme Francio; Duran, Nelson; Costa, Fábio Trindade Maranhão; Oliveira, Alexandre Leite Rodrigues; Höfling, Maria Alice da Cruz; Machado, Dagmar Ruth Stach; Thomé, Rodolfo

    2015-01-01

    Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola), a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg) via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE)-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+). We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation) and stimulation of regulatory T cells (in chronic inflammation). New studies must be conducted in order to

  4. Vagus Nerve through α7 nAChR Modulates Lung Infection and Inflammation: Models, Cells, and Signals

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    Haiya Wu

    2014-01-01

    Full Text Available Cholinergic anti-inflammatory pathway (CAP bridges immune and nervous systems and plays pleiotropic roles in modulating inflammation in animal models by targeting different immune, proinflammatory, epithelial, endothelial, stem, and progenitor cells and signaling pathways. Acute lung injury (ALI is a devastating inflammatory disease. It is pathogenically heterogeneous and involves many cells and signaling pathways. Here, we emphasized the research regarding the modulatory effects of CAP on animal models, cell population, and signaling pathways that involved in the pathogenesis of ALI. By comparing the differential effects of CAP on systemic and pulmonary inflammation, we postulated that a pulmonary parasympathetic inflammatory reflex is formed to sense and respond to pathogens in the lung. Work targeting the formation and function of pulmonary parasympathetic inflammatory reflex would extend our understanding of how vagus nerve senses, recognizes, and fights with pathogens and inflammatory responses.

  5. Airborne pollutant ROFA enhances the allergic airway inflammation through direct modulation of dendritic cells in an uptake-dependent mechanism.

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    Arantes-Costa, Fernanda Magalhaes; Grund, Lidiane Zito; Martins, Milton Arruda; Lima, Carla

    2014-09-01

    Studies suggest that airborne pollutants are important cofactors in the exacerbation of lung diseases. The role of DC on the exacerbation of lung inflammation induced by particulate matter pollutants is unclear. We evaluated the effects of residual oil fly ash (ROFA) on the phenotype and function of bone marrow-derived dendritic cells (BMDCs) in vitro and lung dendritic cells (DCs) in vivo, and the subsequent T-cell response. In a model of asthma, exposure to ROFA exacerbated pulmonary inflammation, which was attributed to the increase of eosinophils, IL-5- and IFN-γ-producing T cells, and goblet cells as well as decreased number of Treg and pDC. However, the ROFA showed no ability to modulate the production of anaphylactic IgE. In vitro studies showed that ROFA directly induced the maturation of DCs up-regulating the expression of co-stimulatory molecules and cytokines and MMP production in an uptake-dependent and oxidative stress-dependent manner. Furthermore, ROFA-pulsed BMDC transferred to allergic mice exacerbated eosinophilic inflammation as well as promoted increased epithelial and goblet cells changes. Thus, pollutants may constitute an important and risk factor in the exacerbation of asthma with inhibition of the negative regulatory signals in the lung, with enhanced mDC activation that sustains the recruitment of effector T lymphocytes and eosinophil. PMID:24975839

  6. Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment.

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    Hong, Gyong Hwa; Kwon, Hyouk-Soo; Moon, Keun-Ai; Park, So Young; Park, Sunjoo; Lee, Kyoung Young; Ha, Eun Hee; Kim, Tae-Bum; Moon, Hee-Bom; Lee, Heung Kyu; Cho, You Sook

    2016-03-01

    Recruitment and activation of dendritic cells (DCs) in the lungs are critical for Th2 responses in asthma, and CCL20 secreted from bronchial epithelial cells (BECs) is known to influence the recruitment of DCs. Because asthma is a disease that is closely associated with oxidative stress, we hypothesized that clusterin, an oxidative stress regulatory molecule, may have a role in the development of allergic airway inflammation. The aim of this study was to examine whether clusterin regulates CCL20 production from the BECs and the subsequent DC recruitment in the lungs. To verify the idea, clusterin knockout (Clu(-/-)), clusterin heterogeneous (Clu(+/-)), and wild-type mice were exposed intranasally to house dust mite (HDM) extract to induce allergic airway inflammation. We found that the total number of immune cells in bronchoalveolar lavage fluid and the lung was increased in Clu(-/-) and Clu(+/-) mice. Of these immune cells, inflammatory DCs (CD11b(+)CD11c(+)) and Ly6C(high) monocyte populations in the lung were significantly increased, which was accompanied by increased levels of various chemokines, including CCL20 in bronchoalveolar lavage fluid, and increased oxidative stress markers in the lung. Moreover, HDM-stimulated human BECs with either up- or downregulated clusterin expression showed that CCL20 secretion was negatively associated with clusterin expression. Interestingly, clusterin also reduced the level of intracellular reactive oxygen species, which is related to induction of CCL20 expression after HDM stimulation. Thus, the antioxidant property of clusterin is suggested to regulate the expression of CCL20 in BECs and the subsequent recruitment of inflammatory DCs in the airway. PMID:26826245

  7. Mesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis.

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    Hao Jia Wu

    Full Text Available Bone marrow-derived mesenchymal stem cells (BM-MSCs have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-α, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-κB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and α-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF and TNFα-stimulating gene (TSG-6 via P38 and NF-κB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-α overexpression were suppressed by recombinant HGF treatment, while the upregulation of α-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, α-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6.

  8. Mesenchymal Stem Cells Modulate Albumin-Induced Renal Tubular Inflammation and Fibrosis

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    Wu, Hao Jia; Yiu, Wai Han; Li, Rui Xi; Wong, Dickson W. L.; Leung, Joseph C. K.; Chan, Loretta Y. Y.; Zhang, Yuelin; Lian, Qizhou; Lin, Miao; Tse, Hung Fat; Lai, Kar Neng; Tang, Sydney C. W.

    2014-01-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD) models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT) under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs) and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-α, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-κB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and α-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF) and TNFα-stimulating gene (TSG)-6 via P38 and NF-κB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-α overexpression were suppressed by recombinant HGF treatment, while the upregulation of α-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, α-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6. PMID:24646687

  9. Dietary Modulation of Inflammation-Induced Colorectal Cancer through PPARγ

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    Ashlee B. Carter

    2009-01-01

    Full Text Available Mounting evidence suggests that the risk of developing colorectal cancer (CRC is dramatically increased for patients with chronic inflammatory diseases. For instance, patients with Crohn's Disease (CD or Ulcerative Colitis (UC have a 12–20% increased risk for developing CRC. Preventive strategies utilizing nontoxic natural compounds that modulate immune responses could be successful in the suppression of inflammation-driven colorectal cancer in high-risk groups. The increase of peroxisome proliferator-activated receptor-γ (PPAR-γ expression and its transcriptional activity has been identified as a target for anti-inflammatory efforts, and the suppression of inflammation-driven colon cancer. PPARγ down-modulates inflammation and elicits antiproliferative and proapoptotic actions in epithelial cells. All of which may decrease the risk for inflammation-induced CRC. This review will focus on the use of orally active, naturally occurring chemopreventive approaches against inflammation-induced CRC that target PPARγ and therefore down-modulate inflammation.

  10. Modulation of Macrophage Efferocytosis in Inflammation

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    Darlynn R Korns

    2011-11-01

    Full Text Available A critical function of macrophages within the inflammatory milieu is the removal of dying cells by a specialized phagocytic process called efferocytosis (to carry to the grave. Through specific receptor engagement and induction of downstream signaling, efferocytosing macrophages promote resolution of inflammation by i efficiently engulfing dying cells, thus avoiding cellular disruption and release of inflammatory contents, and ii producing anti-inflammatory mediators such as IL-10 and TGF-β that dampen pro-inflammatory responses. Evidence suggests that plasticity in macrophage programming, in response to changing environmental cues, modulates efferocytic capability. Essential to programming for enhanced efferocytosis is activation of the nuclear receptors PPARγ, PPARδ, LXR and possibly RXRα. Additionally, a number of signals in the inflammatory milieu, including those from dying cells themselves, can influence efferocytic efficacy either by acting as immediate inhibitors/enhancers or by altering macrophage programming for longer-term effects. Importantly, sustained inflammatory programming of macrophages can lead to defective apoptotic cell clearance and is associated with development of autoimmunity and other chronic inflammatory disorders. This review summarizes the current knowledge of the multiple factors that modulate macrophage efferocytic ability and highlights emerging therapeutic targets with significant potential for limiting chronic inflammation.

  11. Inflammation Modulates RLIP76/RALBP1 Electrophile-Glutathione Conjugate Transporter and Housekeeping Genes in Human Blood-Brain Barrier Endothelial Cells.

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    Barbara Bennani-Baiti

    Full Text Available Endothelial cells are often present at inflammation sites. This is the case of endothelial cells of the blood-brain barrier (BBB of patients afflicted with neurodegenerative disorders such as Alzheimer's, Parkinson's, or multiple sclerosis, as well as in cases of bacterial meningitis, trauma, or tumor-associated ischemia. Inflammation is a known modulator of gene expression through the activation of transcription factors, mostly NF-κB. RLIP76 (a.k.a. RALBP1, an ATP-dependent transporter of electrophile-glutathione conjugates, modulates BBB permeability through the regulation of tight junction function, cell adhesion, and exocytosis. Genes and pathways regulated by RLIP76 are transcriptional targets of tumor necrosis factor alpha (TNF-α pro-inflammatory molecule, suggesting that RLIP76 may also be an inflammation target. To assess the effects of TNF-α on RLIP76, we faced the problem of choosing reference genes impervious to TNF-α. Since such genes were not known in human BBB endothelial cells, we subjected these to TNF-α, and measured by quantitative RT-PCR the expression of housekeeping genes commonly used as reference genes. We find most to be modulated, and analysis of several inflammation datasets as well as a metaanalysis of more than 5000 human tissue samples encompassing more than 300 cell types and diseases show that no single housekeeping gene may be used as a reference gene. Using three different algorithms, however, we uncovered a reference geneset impervious to TNF-α, and show for the first time that RLIP76 expression is induced by TNF-α and follows the induction kinetics of inflammation markers, suggesting that inflammation can influence RLIP76 expression at the BBB. We also show that MRP1 (a.k.a. ABCC1, another electrophile-glutathione transporter, is not modulated in the same cells and conditions, indicating that RLIP76 regulation by TNF-α is not a general property of glutathione transporters. The reference geneset

  12. Pycnogenol modulates apoptosis by suppressing oxidative stress and inflammation in high glucose-treated renal tubular cells.

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    Kim, You Jung; Kim, Young Ae; Yokozawa, Takako

    2011-09-01

    Compelling evidence indicates that polyphenolic antioxidants protect against diabetic nephropathy. Pycnogenol is made up of flavonoids, mainly procyanidins and phenolic compounds, and is a known powerful antioxidant. Hyperglycemia is characteristic of diabetic nephropathy and induces renal tubular cell apoptosis. Thus, in this study, we used high glucose-treated renal tubular cells to investigate the protective action of pycnogenol against high glucose-induced apoptosis and diabetic nephropathy. We also sought to further delineate the underlying mechanisms elicited by oxidative stress and inflammation and suppressed by pycnogenol. Results show that pycnogenol significantly suppressed the high glucose-induced morphological changes and the reduction in cell viability associated with cytotoxicity. Bcl2/Bax protein levels indicated pycnogenol's anti-apoptotic effect against high glucose-induced apoptotic cell death. In addition, several key markers of oxidative stress and inflammation were measured for pycnogenol's beneficial effects. Results indicate pycnogenol's anti-oxidative and anti-inflammatory efficacy in suppressing lipid peroxidation, total reactive species (RS), superoxide ((·)O(2)), nitric oxide (NO(·)), peroxynitrite (ONOO(-)), pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB) nuclear translocation. Based on these results, we conclude that pycnogenol's anti-oxidative and anti-inflammatory properties underlie its anti-apoptotic effects, suggesting further investigation of pycnogenol as a promising treatment against diabetic nephropathy. PMID:21689714

  13. Metabolic Inflammation-Differential Modulation by Dietary Constituents

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    Lyons, Claire L.; Elaine B. Kennedy; Roche, Helen M.

    2016-01-01

    Obesity arises from a sustained positive energy balance which triggers a pro-inflammatory response, a key contributor to metabolic diseases such as T2D. Recent studies, focused on the emerging area of metabolic-inflammation, highlight that specific metabolites can modulate the functional nature and inflammatory phenotype of immune cells. In obesity, expanding adipose tissue attracts immune cells, creating an inflammatory environment within this fatty acid storage organ. Resident immune cells ...

  14. Metabolic Inflammation-Differential Modulation by Dietary Constituents.

    Science.gov (United States)

    Lyons, Claire L; Kennedy, Elaine B; Roche, Helen M

    2016-01-01

    Obesity arises from a sustained positive energy balance which triggers a pro-inflammatory response, a key contributor to metabolic diseases such as T2D. Recent studies, focused on the emerging area of metabolic-inflammation, highlight that specific metabolites can modulate the functional nature and inflammatory phenotype of immune cells. In obesity, expanding adipose tissue attracts immune cells, creating an inflammatory environment within this fatty acid storage organ. Resident immune cells undergo both a pro-inflammatory and metabolic switch in their function. Inflammatory mediators, such as TNF-α and IL-1β, are induced by saturated fatty acids and disrupt insulin signaling. Conversely, monounsaturated and polyunsaturated fatty acids do not interrupt metabolism and inflammation to the same extent. AMPK links inflammation, metabolism and T2D, with roles to play in all and is influenced negatively by obesity. Lipid spillover results in hepatic lipotoxicity and steatosis. Also in skeletal muscle, excessive FFA can impede insulin's action and promote inflammation. Ectopic fat can also affect pancreatic β-cell function, thereby contributing to insulin resistance. Therapeutics, lifestyle changes, supplements and dietary manipulation are all possible avenues to combat metabolic inflammation and the subsequent insulin resistant state which will be explored in the current review. PMID:27128935

  15. Metabolic Inflammation-Differential Modulation by Dietary Constituents

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    Claire L. Lyons

    2016-04-01

    Full Text Available Obesity arises from a sustained positive energy balance which triggers a pro-inflammatory response, a key contributor to metabolic diseases such as T2D. Recent studies, focused on the emerging area of metabolic-inflammation, highlight that specific metabolites can modulate the functional nature and inflammatory phenotype of immune cells. In obesity, expanding adipose tissue attracts immune cells, creating an inflammatory environment within this fatty acid storage organ. Resident immune cells undergo both a pro-inflammatory and metabolic switch in their function. Inflammatory mediators, such as TNF-α and IL-1β, are induced by saturated fatty acids and disrupt insulin signaling. Conversely, monounsaturated and polyunsaturated fatty acids do not interrupt metabolism and inflammation to the same extent. AMPK links inflammation, metabolism and T2D, with roles to play in all and is influenced negatively by obesity. Lipid spillover results in hepatic lipotoxicity and steatosis. Also in skeletal muscle, excessive FFA can impede insulin’s action and promote inflammation. Ectopic fat can also affect pancreatic β-cell function, thereby contributing to insulin resistance. Therapeutics, lifestyle changes, supplements and dietary manipulation are all possible avenues to combat metabolic inflammation and the subsequent insulin resistant state which will be explored in the current review.

  16. p-Cresol affects reactive oxygen species generation, cell cycle arrest, cytotoxicity and inflammation/atherosclerosis-related modulators production in endothelial cells and mononuclear cells.

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    Mei-Chi Chang

    Full Text Available AIMS: Cresols are present in antiseptics, coal tar, some resins, pesticides, and industrial solvents. Cresol intoxication leads to hepatic injury due to coagulopathy as well as disturbance of hepatic circulation in fatal cases. Patients with uremia suffer from cardiovascular complications, such as atherosclerosis, thrombosis, hemolysis, and bleeding, which may be partly due to p-cresol toxicity and its effects on vascular endothelial and mononuclear cells. Given the role of reactive oxygen species (ROS and inflammation in vascular thrombosis, the objective of this study was to evaluate the effect of p-cresol on endothelial and mononuclear cells. METHODS: EA.hy926 (EAHY endothelial cells and U937 cells were exposed to different concentrations of p-cresol. Cytotoxicity was evaluated by 3-(4,5-Dimethylthiazol-2-yl-2,5 -diphenyltetrazolium bromide (MTT assay and trypan blue dye exclusion technique, respectively. Cell cycle distribution was analyzed by propidium iodide flow cytometry. Endothelial cell migration was studied by wound closure assay. ROS level was measured by 2',7'-dichlorofluorescein diacetate (DCF fluorescence flow cytometry. Prostaglandin F2α (PGF2α, plasminogen activator inhibitor-1 (PAI-1, soluble urokinase plasminogen activator receptor (suPAR, and uPA production were determined by Enzyme-linked immunosorbant assay (ELISA. RESULTS: Exposure to 100-500 µM p-cresol decreased EAHY cell number by 30-61%. P-cresol also decreased the viability of U937 mononuclear cells. The inhibition of EAHY and U937 cell growth by p-cresol was related to induction of S-phase cell cycle arrest. Closure of endothelial wounds was inhibited by p-cresol (>100 µM. P-cresol (>50 µM also stimulated ROS production in U937 cells and EAHY cells but to a lesser extent. Moreover, p-cresol markedly stimulated PAI-1 and suPAR, but not PGF2α, and uPA production in EAHY cells. CONCLUSIONS: p-Cresol may contribute to atherosclerosis and thrombosis in patients with

  17. Prostanoids modulate inflammation and alloimmune responses during graft rejection

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    P.N. Rocha

    2005-12-01

    Full Text Available Acute rejection of a transplanted organ is characterized by intense inflammation within the graft. Yet, for many years transplant researchers have overlooked the role of classic mediators of inflammation such as prostaglandins and thromboxane (prostanoids in alloimmune responses. It has been demonstrated that local production of prostanoids within the allograft is increased during an episode of acute rejection and that these molecules are able to interfere with graft function by modulating vascular tone, capillary permeability, and platelet aggregation. Experimental data also suggest that prostanoids may participate in alloimmune responses by directly modulating T lymphocyte and antigen-presenting cell function. In the present paper, we provide a brief overview of the alloimmune response, of prostanoid biology, and discuss the available evidence for the role of prostaglandin E2 and thromboxane A2 in graft rejection.

  18. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

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    Highlights: → Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. → Induction of CD4+CD25+Foxp3+ T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. → C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4+CD25+Foxp3+ regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical relationship between the allergic immune response and

  19. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture.

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    Muir, Peter; Hans, Eric C; Racette, Molly; Volstad, Nicola; Sample, Susannah J; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L; Bloom, Debra D; Bleedorn, Jason A; Hao, Zhengling; Amene, Ermias; Suresh, M; Hematti, Peiman

    2016-01-01

    Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response

  20. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture

    Science.gov (United States)

    Muir, Peter; Hans, Eric C.; Racette, Molly; Volstad, Nicola; Sample, Susannah J.; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L.; Bloom, Debra D.; Bleedorn, Jason A.; Hao, Zhengling; Amene, Ermias; Suresh, M.; Hematti, Peiman

    2016-01-01

    Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response

  1. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions.

    Science.gov (United States)

    Jeong, Young-Il; Kim, Seung Hyun; Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja; Park, Jin Wook; Park, Yeong-Min; Lee, Sang Eun

    2011-04-22

    Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naïve T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical relationship between the allergic immune response and helminth infection. PMID:21440530

  2. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young-Il [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Kim, Seung Hyun [Div. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Park, Jin Wook; Park, Yeong-Min [Dept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San (Korea, Republic of); Lee, Sang Eun, E-mail: ondalgl@cdc.go.kr [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)

    2011-04-22

    Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical

  3. A novel shogaol analog suppresses cancer cell invasion and inflammation, and displays cytoprotective effects through modulation of NF-κB and Nrf2-Keap1 signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Fei-Fei; Ling, Hui; Ang, Xiaohui; Reddy, Shridhivya A.; Lee, Stephanie S-H.; Yang, Hong; Tan, Sock-Hoon [Department of Pharmacy, Faculty of Science, National University of Singapore (Singapore); Hayes, John D. [Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland (United Kingdom); Chui, Wai-Keung [Department of Pharmacy, Faculty of Science, National University of Singapore (Singapore); Chew, Eng-Hui, E-mail: phaceh@nus.edu.sg [Department of Pharmacy, Faculty of Science, National University of Singapore (Singapore)

    2013-11-01

    Natural compounds containing vanilloid and Michael acceptor moieties appear to possess anti-cancer and chemopreventive properties. The ginger constituent shogaol represents one such compound. In this study, the anti-cancer potential of a synthetic novel shogaol analog 3-phenyl-3-shogaol (3-Ph-3-SG) was assessed by evaluating its effects on signaling pathways. At non-toxic concentrations, 3-Ph-3-SG suppressed cancer cell invasion in MDA-MB-231 and MCF-7 breast carcinoma cells through inhibition of PMA-activated MMP-9 expression. At similar concentrations, 3-Ph-3-SG reduced expression of the inflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and prostanglandin-E{sub 2} (PGE{sub 2}) in RAW 264.7 macrophage-like cells. Inhibition of cancer cell invasion and inflammation by 3-Ph-3-SG were mediated through suppression of the nuclear factor-kappaB (NF-κB) signaling pathway. The 3-Ph-3-SG also demonstrated cytoprotective effects by inducing the antioxidant response element (ARE)-driven genes NAD(P)H quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1). Cytoprotection by 3-Ph-3-SG was achieved at least partly through modification of cysteine residues in the E3 ubiquitin ligase substrate adaptor Kelch-like ECH-associated protein 1 (Keap1), which resulted in accumulation of transcription factor NF-E2 p45-related factor 2 (Nrf2). The activities of 3-Ph-3-SG were comparable to those of 6-shogaol, the most abundant naturally-occurring shogaol, and stronger than those of 4-hydroxyl-null deshydroxy-3-phenyl-3-shogaol, which attested the importance of the 4-hydroxy substituent in the vanilloid moiety for bioactivity. In summary, 3-Ph-3-SG is shown to possess activities that modulate stress-associated pathways relevant to multiple steps in carcinogenesis. Therefore, it warrants further investigation of this compound as a promising candidate for use in chemotherapeutic and chemopreventive strategies. - Highlights:

  4. Preventative Effect of an Herbal Preparation (HemoHIM) on Development of Airway Inflammation in Mice via Modulation of Th1/2 Cells Differentiation

    Science.gov (United States)

    Kim, Jong-Jin; Cho, Hyun Wook; Park, Hae-Ran; Jung, Uhee; Jo, Sung-Kee; Yee, Sung-Tae

    2013-01-01

    HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4+ T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4+ T cells displayed increased Th1 (IFN-γ+ cell) as well as decreased Th2 (IL-4+ cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance. PMID:23844220

  5. Preventative effect of an herbal preparation (HemoHIM) on development of airway inflammation in mice via modulation of Th1/2 cells differentiation.

    Science.gov (United States)

    Kim, Jong-Jin; Cho, Hyun Wook; Park, Hae-Ran; Jung, Uhee; Jo, Sung-Kee; Yee, Sung-Tae

    2013-01-01

    HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4(+) T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4(+) T cells displayed increased Th1 (IFN-γ(+) cell) as well as decreased Th2 (IL-4(+) cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance. PMID:23844220

  6. Preventative effect of an herbal preparation (HemoHIM on development of airway inflammation in mice via modulation of Th1/2 cells differentiation.

    Directory of Open Access Journals (Sweden)

    Jong-Jin Kim

    Full Text Available HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4(+ T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA. In an in vitro experiment, naive CD4(+ T cells displayed increased Th1 (IFN-γ(+ cell as well as decreased Th2 (IL-4(+ cell differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13 levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight pretreatment (4 weeks. These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance.

  7. Preventative effect of an herbal preparation (HemoHIM) on development of airway inflammation in mice via modulation of Th1/2 cells differentiation.

    Science.gov (United States)

    Kim, Jong-Jin; Cho, Hyun Wook; Park, Hae-Ran; Jung, Uhee; Jo, Sung-Kee; Yee, Sung-Tae

    2013-01-01

    HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4(+) T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4(+) T cells displayed increased Th1 (IFN-γ(+) cell) as well as decreased Th2 (IL-4(+) cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance.

  8. Dysregulated cytokine expression by CD4+ T cells from post-septic mice modulates both Th1 and Th2-mediated granulomatous lung inflammation.

    Directory of Open Access Journals (Sweden)

    William F Carson

    Full Text Available Previous epidemiological studies in humans and experimental studies in animals indicate that survivors of severe sepsis exhibit deficiencies in the activation and effector function of immune cells. In particular, CD4+ T lymphocytes can exhibit reduced proliferative capacity and improper cytokine responses following sepsis. To further investigate the cell-intrinsic defects of CD4+ T cells following sepsis, splenic CD4+ T cells from sham surgery and post-septic mice were transferred into lymphopenic mice. These recipient mice were then subjected to both TH1-(purified protein derivative and TH2-(Schistosoma mansoni egg antigen driven models of granulomatous lung inflammation. Post-septic CD4+ T cells mediated smaller TH1 and larger TH2 lung granulomas as compared to mice receiving CD4+ T cells from sham surgery donors. However, cytokine production by lymph node cells in antigen restimulation assays indicated increased pan-specific cytokine expression by post-septic CD4+ T cell recipient mice in both TH1 and TH2 granuloma models. These include increased production of T(H2 cytokines in TH1 inflammation, and increased production of T(H1 cytokines in TH2 inflammation. These results suggest that cell-intrinsic defects in CD4+ T cell effector function can have deleterious effects on inflammatory processes post-sepsis, due to a defect in the proper regulation of TH-specific cytokine expression.

  9. Activation of the retinoid X receptor modulates angiotensin II-induced smooth muscle gene expression and inflammation in vascular smooth muscle cells.

    Science.gov (United States)

    Lehman, Allison M B; Montford, John R; Horita, Henrick; Ostriker, Allison C; Weiser-Evans, Mary C M; Nemenoff, Raphael A; Furgeson, Seth B

    2014-11-01

    The retinoid X receptor (RXR) partners with numerous nuclear receptors, such as the peroxisome proliferator activated receptor (PPAR) family, liver X receptors (LXRs), and farnesoid X receptor (FXR). Although each heterodimer can be activated by specific ligands, a subset of these receptors, defined as permissive nuclear receptors, can also be activated by RXR agonists known as rexinoids. Many individual RXR heterodimers have beneficial effects in vascular smooth muscle cells (SMCs). Because rexinoids can potently activate multiple RXR pathways, we hypothesized that treating SMCs with rexinoids would more effectively reverse the pathophysiologic effects of angiotensin II than an individual heterodimer agonist. Cultured rat aortic SMCs were pretreated with either an RXR agonist (bexarotene or 9-cis retinoic acid) or vehicle (dimethylsulfoxide) for 24 hours before stimulation with angiotensin II. Compared with dimethylsulfoxide, bexarotene blocked angiotensin II-induced SM contractile gene induction (calponin and smooth muscle-α-actin) and protein synthesis ([(3)H]leucine incorporation). Bexarotene also decreased angiotensin II-mediated inflammation, as measured by decreased expression of monocyte chemoattractant protein-1 (MCP-1). Activation of p38 mitogen-activated protein (MAP) kinase but not extracellular signal-related kinase (ERK) or protein kinase B (Akt) was also blunted by bexarotene. We compared bexarotene to five agonists of nuclear receptors (PPARα, PPARγ, PPARδ, LXR, and FXR). Bexarotene had a greater effect on calponin reduction, MCP-1 inhibition, and p38 MAP kinase inhibition than any individual agonist. PPARγ knockout cells demonstrated blunted responses to bexarotene, indicating that PPARγ is necessary for the effects of bexarotene. These data demonstrate that RXR is a potent modulator of angiotensin II-mediated responses in the vasculature, partially through inhibition of p38. PMID:25169989

  10. Medroxyprogesterone Acetate Modulates Remodeling, Immune Cell Census, and Nerve Fibers in the Cervix of a Mouse Model for Inflammation-induced Preterm Birth

    OpenAIRE

    Yellon, Steven M.; Ebner, Charlotte A.; Elovitz, Michal A.

    2008-01-01

    To determine whether a progestational agent can modify inflammation-induced preterm cervical ripening, mice on day 15 of gestation were given an intrauterine injection of (1) saline, (2) lipopolysaccharide, (3) an intramuscular injection of medroxyprogesterone acetate alone prior to lipopolysaccharide, or (4) medroxyprogesterone acetate alone. Cervices were obtained 6 hours later, then fixed, sectioned, and processed to stain collagen structure or to identify immune cells or nerve fibers. Cer...

  11. Anticoagulant modulation of inflammation in severe sepsis

    OpenAIRE

    Allen, Karen S; Sawheny, Eva; Kinasewitz, Gary T

    2015-01-01

    Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by ...

  12. p-Cresol Affects Reactive Oxygen Species Generation, Cell Cycle Arrest, Cytotoxicity and Inflammation/Atherosclerosis-Related Modulators Production in Endothelial Cells and Mononuclear Cells

    OpenAIRE

    Mei-Chi Chang; Hsiao-Hua Chang; Chiu-Po Chan; Sin-Yuet Yeung; Hsiang-Chi Hsien; Bor-Ru Lin; Chien-Yang Yeh; Wan-Yu Tseng; Shui-Kuan Tseng; Jiiang-Huei Jeng

    2014-01-01

    AIMS: Cresols are present in antiseptics, coal tar, some resins, pesticides, and industrial solvents. Cresol intoxication leads to hepatic injury due to coagulopathy as well as disturbance of hepatic circulation in fatal cases. Patients with uremia suffer from cardiovascular complications, such as atherosclerosis, thrombosis, hemolysis, and bleeding, which may be partly due to p-cresol toxicity and its effects on vascular endothelial and mononuclear cells. Given the role of reactive oxygen sp...

  13. Anticoagulant modulation of inflammation in severe sepsis.

    Science.gov (United States)

    Allen, Karen S; Sawheny, Eva; Kinasewitz, Gary T

    2015-05-01

    Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by inhibiting thrombin generation with heparin and or endogenous anticoagulants are reviewed. In general, these trials have failed to demonstrate that anticoagulant therapy is associated with improvement in mortality or morbidity. While it is possible that selective patients who are severely ill with a high expected mortality may be shown to benefit from such therapy, at the present time none of these anticoagulants are neither approved nor can they be recommended for the treatment of sepsis. PMID:25938026

  14. Interleukin-5 modulates interleukin-8 secretion in eosinophilic inflammation

    Directory of Open Access Journals (Sweden)

    L. H. Faccioli

    1998-01-01

    Full Text Available Serum and BALF (bronchoalveolar lavage fluid IL-8 levels and serum levels were investigated in Tox ocara canis infected guinea-pigs and the role of IL-5 as a modulator of cytokine secretion was studied. Serum levels increased early in infected animals, exceeding control levels 4 h after infection, peaked between days 6 and 18, and continued to exceed control levels after 48 days of infection. Serum and BALF IL-8 levels showed the same profile as blood eosinophilia, increasing 6 days post-infection and peaking between days 18 and 24. Treatment of infected animals with anti-IL-5 Ab suppressed eosinophilia with a parallel increase in blood IL-8 levels, whereas no change was found in levels. To support our in vivo observation we carried out experiments in vitro using guinea-pig LPS-stimulated adherent peritoneal cells which release large amounts of IL-8 into the supernatants. When rIL-5 was added to LPS-stimulated cells, 65% inhibition of IL-8 release into the supernatants was observed. Pre-incubation of cells with anti-IL-5 Ab prevented the inhibition of IL-8 release into the supernatants induced by rIL-5. Our results demonstrate for the first time that TNF- α and IL-8 are released concomitant with or after IL-5 in the eosinophilic inflammation induced by T. canis . Moreover, in addition to showing that IL-5 is fundamental for the induction of blood eosinophilia, the present results suggest that this cytokine may play a new biological role by acting as modulator of IL-8 secretion.

  15. Lipidosterolic Extract of Serenoa Repens Modulates the Expression of Inflammation Related-Genes in Benign Prostatic Hyperplasia Epithelial and Stromal Cells

    Directory of Open Access Journals (Sweden)

    Stéphane Terry

    2013-07-01

    Full Text Available Despite the high prevalence of histological Benign Prostatic Hypeplasia (BPH in elderly men, little is known regarding the molecular mechanisms and networks underlying the development and progression of the disease. Here, we explored the effects of a phytotherapeutic agent, Lipidosterolic extract of the dwarf palm plant Serenoa repens (LSESr, on the mRNA gene expression profiles of two representative models of BPH, BPH1 cell line and primary stromal cells derived from BPH. Treatment of these cells with LSESr significantly altered gene expression patterns as assessed by comparative gene expression profiling on gene chip arrays. The expression changes were manifested three hours following in vitro administration of LSESr, suggesting a rapid action for this compound. Among the genes most consistently affected by LSESr treatment, we found numerous genes that were categorized as part of proliferative, apoptotic, and inflammatory pathways. Validation studies using quantitative real-time PCR confirmed the deregulation of genes known to exhibit key roles in these biological processes including IL1B, IL1A, CXCL6, IL1R1, PTGS2, ALOX5, GAS1, PHLDA1, IL6, IL8, NFkBIZ, NFKB1, TFRC, JUN, CDKN1B, and ERBB3. Subsequent analyses also indicated that LSESr treatment can impede the stimulatory effects of certain proinflammatory cytokines such as IL6, IL17, and IL15 in these cells. These results suggest that LSESr may be useful to treat BPH that manifest inflammation characteristics. This also supports a role for inflammation in BPH presumably by mediating the balance between apoptosis and proliferation.

  16. Does Branched-Chain Amino Acids Supplementation Modulate Skeletal Muscle Remodeling through Inflammation Modulation? Possible Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Humberto Nicastro

    2012-01-01

    Full Text Available Skeletal muscle protein turnover is modulated by intracellular signaling pathways involved in protein synthesis, degradation, and inflammation. The proinflammatory status of muscle cells, observed in pathological conditions such as cancer, aging, and sepsis, can directly modulate protein translation initiation and muscle proteolysis, contributing to negative protein turnover. In this context, branched-chain amino acids (BCAAs, especially leucine, have been described as a strong nutritional stimulus able to enhance protein translation initiation and attenuate proteolysis. Furthermore, under inflammatory conditions, BCAA can be transaminated to glutamate in order to increase glutamine synthesis, which is a substrate highly consumed by inflammatory cells such as macrophages. The present paper describes the role of inflammation on muscle remodeling and the possible metabolic and cellular effects of BCAA supplementation in the modulation of inflammatory status of skeletal muscle and the consequences on protein synthesis and degradation.

  17. Regulation of pulmonary inflammation by mesenchymal cells

    NARCIS (Netherlands)

    Alkhouri, Hatem; Poppinga, Wilfred Jelco; Tania, Navessa Padma; Ammit, Alaina; Schuliga, Michael

    2014-01-01

    Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue

  18. Copycat innate lymphoid cells dampen gut inflammation.

    OpenAIRE

    Magri, Giuliana; Cerutti, Andrea

    2015-01-01

    The mechanisms whereby the gut mucosa tolerates trillions of commensal bacteria without developing inflammation remain poorly understood. A recent Science article reveals that gut innate lymphoid cells constrain inflammatory T cell responses to commensal bacteria by adopting a strategy usually deployed by thymic epithelial cells to negatively select self-reactive T cells.

  19. Polyphenolic extracts from cowpea (Vigna unguiculata) protect colonic myofibroblasts (CCD18Co cells) from lipopolysaccharide (LPS)-induced inflammation--modulation of microRNA 126.

    Science.gov (United States)

    Ojwang, Leonnard O; Banerjee, Nivedita; Noratto, Giuliana D; Angel-Morales, Gabriela; Hachibamba, Twambo; Awika, Joseph M; Mertens-Talcott, Susanne U

    2015-01-01

    Cowpea (Vigna unguiculata) is a drought tolerant crop with several agronomic advantages over other legumes. This study evaluated varieties from four major cowpea phenotypes (black, red, light brown and white) containing different phenolic profiles for their anti-inflammatory property on non-malignant colonic myofibroblasts (CCD18Co) cells challenged with an endotoxin (lipopolysaccharide, LPS). Intracellular reactive oxygen species (ROS) assay on the LPS-stimulated cells revealed antioxidative potential of black and red cowpea varieties. Real-time qRT-PCR analysis in LPS-stimulated cells revealed down-regulation of proinflammatory cytokines (IL-8, TNF-α, VCAM-1), transcription factor NF-κB and modulation of microRNA-126 (specific post-transcriptional regulator of VCAM-1) by cowpea polyphenolics. The ability of cowpea polyphenols to modulate miR-126 signaling and its target gene VCAM-1 were studied in LPS-stimulated endothelial cells transfected with a specific inhibitor of miR-126, and treated with 10 mg GAE/L black cowpea extract where the extract in part reversed the effect of the miR-126 inhibitor. This suggests that cowpea may exert their anti-inflammatory activities at least in part through induction of miR-126 that then down-regulate VCAM-1 mRNA and protein expressions. Overall, Cowpea therefore is promising as an anti-inflammatory dietary component. PMID:25300227

  20. The PPAR-Platelet Connection: Modulators of Inflammation and Potential Cardiovascular Effects

    Directory of Open Access Journals (Sweden)

    S. L. Spinelli

    2008-01-01

    Full Text Available Historically, platelets were viewed as simple anucleate cells responsible for initiating thrombosis and maintaining hemostasis, but clearly they are also key mediators of inflammation and immune cell activation. An emerging body of evidence links platelet function and thrombosis to vascular inflammation. peroxisome proliferator-activated receptors (PPARs play a major role in modulating inflammation and, interestingly, PPARs (PPARβ/δ and PPARγ were recently identified in platelets. Additionally, PPAR agonists attenuate platelet activation; an important discovery for two reasons. First, activated platelets are formidable antagonists that initiate and prolong a cascade of events that contribute to cardiovascular disease (CVD progression. Dampening platelet release of proinflammatory mediators, including CD40 ligand (CD40L, CD154, is essential to hinder this cascade. Second, understanding the biologic importance of platelet PPARs and the mechanism(s by which PPARs regulate platelet activation will be imperative in designing therapeutic strategies lacking the deleterious or unwanted side effects of current treatment options.

  1. The PPAR-Platelet Connection: Modulators of Inflammation and Potential Cardiovascular Effects.

    Science.gov (United States)

    Spinelli, S L; O'Brien, J J; Bancos, S; Lehmann, G M; Springer, D L; Blumberg, N; Francis, C W; Taubman, M B; Phipps, R P

    2008-01-01

    Historically, platelets were viewed as simple anucleate cells responsible for initiating thrombosis and maintaining hemostasis, but clearly they are also key mediators of inflammation and immune cell activation. An emerging body of evidence links platelet function and thrombosis to vascular inflammation. peroxisome proliferator-activated receptors (PPARs) play a major role in modulating inflammation and, interestingly, PPARs (PPARbeta/delta and PPARgamma) were recently identified in platelets. Additionally, PPAR agonists attenuate platelet activation; an important discovery for two reasons. First, activated platelets are formidable antagonists that initiate and prolong a cascade of events that contribute to cardiovascular disease (CVD) progression. Dampening platelet release of proinflammatory mediators, including CD40 ligand (CD40L, CD154), is essential to hinder this cascade. Second, understanding the biologic importance of platelet PPARs and the mechanism(s) by which PPARs regulate platelet activation will be imperative in designing therapeutic strategies lacking the deleterious or unwanted side effects of current treatment options.

  2. Bioactive lipids as modulators of immunity, inflammation and emotions.

    Science.gov (United States)

    Chiurchiù, Valerio; Maccarrone, Mauro

    2016-08-01

    Lipids are not only constituents of cellular membranes but also key signaling mediators, thus acting as 'bioactive lipids'. Among the prominent roles exerted by bioactive lipids are immune regulation, inflammation and maintenance of homeostasis. Accumulated evidence indicates the existence of a bidirectional relationship between immune and nervous systems, whereby inflammatory mediators can directly modulate emotions that, in turn, can strongly influence immune responses, thus affecting health. This review summarizes current knowledge on the ability of several families of bioactive lipids to regulate immunity and inflammation (through pro-inflammatory or anti-inflammatory effects), as well as to control emotions and mood-related manifestations, advocating these substances as an attractive interface between 'mind' and 'body', and as a potential target to treat inflammatory/immune-mediated mood disorders. PMID:27372887

  3. Bupleurum Polysaccharides Attenuates Lipopolysaccharide-Induced Inflammation via Modulating Toll-Like Receptor 4 Signaling

    OpenAIRE

    Wu, Jian; Zhang, Yun-Yi; Guo, Li; LI Hong; Chen, Dao-Feng

    2013-01-01

    Background Bupleurum polysaccharides (BPs), isolated from Bupleurum smithii var. parvifolium, possesses immunomodulatory activity, particularly on inflammation. Bacterial endotoxin lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor 4 (TLR4) on host cell membrane. The present study was performed to evaluate whether the therapeutic efficacy of BPs on suppression of LPS’s pathogenecity could be associated with the modulating of TLR4 signaling pathway. Methodolog...

  4. Curcuma oil attenuates accelerated atherosclerosis and macrophage foam-cell formation by modulating genes involved in plaque stability, lipid homeostasis and inflammation.

    Science.gov (United States)

    Singh, Vishal; Rana, Minakshi; Jain, Manish; Singh, Niharika; Naqvi, Arshi; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

    2015-01-14

    In the present study, the anti-atherosclerotic effect and the underlying mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid ligation (PCL) or FeCl3-induced arterial oxidative injury (Ox-injury) after 1 week of treatment with a high-cholesterol (HC) diet or HC diet plus C. oil (100 and 300 mg/kg, orally). Hamsters fed with the HC diet were analysed at 1, 3 and 5 weeks following carotid injury. The HC diet plus C. oil-fed group was analysed at 5 weeks. In hyperlipidaemic hamsters with PCL or Ox-injury, C. oil (300 mg/kg) reduced elevated plasma and aortic lipid levels, arterial macrophage accumulation, and stenosis when compared with those subjected to arterial injury alone. Similarly, elevated mRNA transcripts of matrix metalloproteinase-2 (MMP-2), MMP-9, cluster of differentiation 45 (CD45), TNF-α, interferon-γ (IFN-γ), IL-1β and IL-6 were reduced in atherosclerotic arteries, while those of transforming growth factor-β (TGF-β) and IL-10 were increased after the C. oil treatment (300 mg/kg). The treatment with C. oil prevented HC diet- and oxidised LDL (OxLDL)-induced lipid accumulation, decreased the mRNA expression of CD68 and CD36, and increased the mRNA expression of PPARα, LXRα, ABCA1 and ABCG1 in both hyperlipidaemic hamster-derived peritoneal and THP-1 macrophages. The administration of C. oil suppressed the mRNA expression of TNF-α, IL-1β, IL-6 and IFN-γ and increased the expression of TGF-β in peritoneal macrophages. In THP-1 macrophages, C. oil supplementation prevented OxLDL-induced production of TNF-α and IL-1β and increased the levels of TGF-β. The present study shows that C. oil attenuates arterial injury-induced accelerated atherosclerosis, inflammation and macrophage foam-cell formation.

  5. Schistosoma mansoni Tegument (Smteg) Induces IL-10 and Modulates Experimental Airway Inflammation

    Science.gov (United States)

    2016-01-01

    Background Previous studies have demonstrated that S. mansoni infection and inoculation of the parasite eggs and antigens are able to modulate airways inflammation induced by OVA in mice. This modulation was associated to an enhanced production of interleukin-10 and to an increased number of regulatory T cells. The S. mansoni schistosomulum is the first stage to come into contact with the host immune system and its tegument represents the host-parasite interface. The schistosomula tegument (Smteg) has never been studied in the context of modulation of inflammatory disorders, although immune evasion mechanisms take place in this phase of infection to guarantee the persistence of the parasite in the host. Methodology and Principal Findings The aim of this study was to evaluate the Smteg ability to modulate inflammation in an experimental airway inflammation model induced by OVA and to characterize the immune factors involved in this modulation. To achieve the objective, BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with OVA aerosol after Smteg intraperitoneal inoculation. Protein extravasation and inflammatory cells were assessed in bronchoalveolar lavage and IgE levels were measured in serum. Additionally, lungs were excised for histopathological analyses, cytokine measurement and characterization of the cell populations. Inoculation with Smteg led to a reduction in the protein levels in bronchoalveolar lavage (BAL) and eosinophils in both BAL and lung tissue. In the lung tissue there was a reduction in inflammatory cells and collagen deposition as well as in IL-5, IL-13, IL-25 and CCL11 levels. Additionally, a decrease in specific anti-OVA IgE levels was observed. The reduction observed in these inflammatory parameters was associated with increased levels of IL-10 in lung tissues. Furthermore, Smteg/asthma mice showed high percentage of CD11b+F4/80+IL-10+ and CD11c+CD11b+IL-10+ cells in lungs. Conclusion Taken together, these findings

  6. Modulation of metabolic syndrome-related inflammation by cocoa.

    Science.gov (United States)

    Gu, Yeyi; Lambert, Joshua D

    2013-06-01

    Cocoa (Theobroma cacao L., Sterculiaceae) is a widely consumed food ingredient. Although typically found in high-fat, high-sugar foods such as chocolate, cocoa is rich in polyphenols, methylxanthines, and monounsaturated fatty acids. There is increasing evidence that moderate consumption of cocoa and cocoa-containing foods may have beneficial effects on the health including vasodilatory, antioxidant, and anti-inflammatory effects. Polyphenols in cocoa, including monomeric flavanols, as well as polymeric proanthocyanidins, may play a role in these observed beneficial effects. Chronic inflammation represents a potential mechanistic link between obesity and its related pathologies: insulin resistance, dyslipidemia, and hypertension, which comprise the metabolic syndrome. In the present review, we discuss the available data regarding the modulation of metabolic syndrome-related inflammation by cocoa and cocoa-derived compounds. We emphasize studies using laboratory animals or human subjects since such studies often represent the strongest available evidence for biological effects. In vitro studies are included to provide some mechanistic context, but are critically interpreted. Although the available data seem to support the anti-inflammatory effects of cocoa, further studies are needed with regard to the dose-response relationship as well as the underlying mechanisms of action. We hope this review will stimulate further research on cocoa and its anti-inflammatory activities. PMID:23637048

  7. Caspase-11 Modulates Inflammation and Attenuates Toxoplasma gondii Pathogenesis.

    Science.gov (United States)

    Coutermarsh-Ott, Sheryl L; Doran, John T; Campbell, Caroline; Williams, Tere M; Lindsay, David S; Allen, Irving C

    2016-01-01

    Toxoplasma gondii is an obligate intracellular parasite that is the etiologic agent responsible for toxoplasmosis. Infection with T. gondii results in activation of nucleotide binding domain and leucine rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1β and IL-18. Recently, a noncanonical inflammasome has been characterized which functions through caspase-11 and appears to augment many biological functions previously considered to be dependent upon the canonical inflammasome. To better elucidate the function of this noncanonical inflammasome in toxoplasmosis, we utilized Asc (-/-) and Casp11 (-/-) mice and infected these animals with T. gondii. Our data indicates that caspase-11 modulates the innate immune response to T. gondii through a mechanism which is distinct from that currently described for the canonical inflammasome. Asc (-/-) mice demonstrated increased disease pathogenesis during the acute phase of T. gondii infection, whereas Casp11 (-/-) mice demonstrated significantly attenuated disease pathogenesis and reduced inflammation. This attenuated host response was associated with reduced local and systemic cytokine production, including diminished IL-1β. During the chronic phase of infection, caspase-11 deficiency resulted in increased neuroinflammation and tissue cyst burden in the brain. Together, our data suggest that caspase-11 functions to protect the host by enhancing inflammation during the early phase of infection in an effort to minimize disease pathogenesis during later stages of toxoplasmosis. PMID:27378827

  8. Estrogen and inflammation modulate estrogen receptor alpha expression in specific tissues of the temporomandibular joint

    Directory of Open Access Journals (Sweden)

    Bellinger Larry L

    2009-12-01

    Full Text Available Abstract Background Estrogen is known to play role in temporomandibular joint (TMJ disorders and estrogen effects can be mediated by estrogen receptor (ER alpha present in the TMJ. Cells expressing the estrogen receptor ERalpha are present in the temporomandibular joint (TMJ but changes in expression due to estrogen and inflammation have not been characterized. In this study, ERalpha protein content and the number of cells expressing ERalpha was measured in 17 beta-estradiol-treated rats after inflammation was induced in the TMJ. Methods Sixteen ovariectomized female rats were divided into two groups such that one group received 17 beta estradiol (E2 and the other was given vehicle (VEH. Groups were then subdivided further, one received injections of saline and the other received Complete Freund's adjuvant (CFA within the superior joint space of the TMJ. Thus the four groups include no E2/saline, E2/saline, no E2/CFA and E2/CFA. After treatment, the rats were sacrificed, and the TMJ anterior, disc, retrodiscal and synovial tissues were analyzed by western blot and immunocytochemistry. Positive stained cells were counted using a Nikon epifluorescent microscope. Results The western blot showed that ERalpha protein significantly decreased with inflammation. The number of ERalpha-positive cells in the TMJ was not affected by inflammation or 17 beta-estradiol with exception of the retrodiscal tissue. In the retrodiscal tissue 17 beta-estradiol significantly decreased the number of ERalpha-positive cells but only in a non-inflamed joint. Conclusions In conclusion, inflammation and 17 beta-estradiol can modulate ERalpha expression in the TMJ but the effects are tissue specific.

  9. Eosinophils in the lung – modulating apoptosis and efferocytosis in airway inflammation

    Directory of Open Access Journals (Sweden)

    Jennifer M Felton

    2014-07-01

    Full Text Available Due to the key role of the lung in efficient transfer of oxygen in exchange for carbon dioxide, a controlled inflammatory response is essential for restoration of tissue homeostasis following airway exposure to bacterial pathogens or environmental toxins. Unregulated or prolonged inflammatory responses in the lungs can lead to tissue damage, disrupting normal tissue architecture and consequently compromising efficient gaseous exchange. Failure to resolve inflammation underlies the development and/or progression of a number of inflammatory lung diseases including asthma. Eosinophils, granulocytic cells of the innate immune system, are primarily involved in defence against parasitic infections. However, the propagation of the allergic inflammatory response in chronic asthma is thought to involve excessive recruitment and impaired apoptosis of eosinophils together with defective phagocytic clearance of apoptotic cells (efferocytosis. In terms of therapeutic approaches for treatment of asthma, the widespread use of glucocorticoids is associated with a number of adverse health consequences after long-term use, while some patients suffer from steroid-resistant disease. A new approach for therapeutic intervention would be to promote the resolution of inflammation via modulation of eosinophil apoptosis and the phagocytic clearance of apoptotic cells. This review focuses on the mechanisms underpinning eosinophil-mediated lung damage, currently available treatments and therapeutic targets that might in future be harnessed to facilitate inflammation resolution by the manipulation of cell survival and clearance pathways.

  10. Eosinophils in the lung - modulating apoptosis and efferocytosis in airway inflammation.

    Science.gov (United States)

    Felton, Jennifer M; Lucas, Christopher D; Rossi, Adriano G; Dransfield, Ian

    2014-01-01

    Due to the key role of the lung in efficient transfer of oxygen in exchange for carbon dioxide, a controlled inflammatory response is essential for restoration of tissue homeostasis following airway exposure to bacterial pathogens or environmental toxins. Unregulated or prolonged inflammatory responses in the lungs can lead to tissue damage, disrupting normal tissue architecture, and consequently compromising efficient gaseous exchange. Failure to resolve inflammation underlies the development and/or progression of a number of inflammatory lung diseases including asthma. Eosinophils, granulocytic cells of the innate immune system, are primarily involved in defense against parasitic infections. However, the propagation of the allergic inflammatory response in chronic asthma is thought to involve excessive recruitment and impaired apoptosis of eosinophils together with defective phagocytic clearance of apoptotic cells (efferocytosis). In terms of therapeutic approaches for the treatment of asthma, the widespread use of glucocorticoids is associated with a number of adverse health consequences after long-term use, while some patients suffer from steroid-resistant disease. A new approach for therapeutic intervention would be to promote the resolution of inflammation via modulation of eosinophil apoptosis and the phagocytic clearance of apoptotic cells. This review focuses on the mechanisms underpinning eosinophil-mediated lung damage, currently available treatments and therapeutic targets that might in future be harnessed to facilitate inflammation resolution by the manipulation of cell survival and clearance pathways. PMID:25071763

  11. Genistein suppresses tumor necrosis factor α-induced inflammation via modulating reactive oxygen species/Akt/nuclear factor ΚB and adenosine monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A cells

    Directory of Open Access Journals (Sweden)

    Li J

    2014-03-01

    Full Text Available Jinchao Li,1,* Jun Li,2,* Ye Yue,1 Yiping Hu,1 Wenxiang Cheng,1 Ruoxi Liu,3 Xiaohua Pan,4 Peng Zhang1 1Center for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 2Emergency Surgery Department, Shaanxi Provincial People’s Hospital, Xi’an, 3Department of Orthopedics, Shandong University of Traditional Chinese Medicine, Jinan, 4Department of Orthopedics, Second Clinical Medical College, Jinan University, Shenzhen, People’ Republic of China *These authors contributed equally to this work Aims: Genistein, an isoflavone derivative found in soy, is known as a promising treatment for rheumatoid arthritis (RA. However, the detailed molecular mechanism of genistein in suppression of proinflammatory cytokine production remains ambiguous. The aim of this work was to evaluate the signal pathway by which genistein modulates inflammatory cytokine expression. Materials and methods: MH7A cells were stimulated with tumor necrosis factor (TNF-α and incubated with genistein, and interleukin (IL-1β, IL-6, and IL-8 production was measured by enzyme-linked immunosorbent assay. Nuclear translocation of nuclear factor (NF- ΚB was measured by a confocal fluorescence microscopy. The intracellular accumulation of reactive oxygen species (ROS was monitored using the fluorescent probe 5-6-chloromethyl-2´,7´-dichlorodihydrofluorescein diacetate. Signal-transduction protein expression was measured by Western blot. Results: Genistein decreased the secretion of IL-1β, IL-6, and IL-8 from TNF-α-stimulated MH7A cells in a dose-dependent manner. Genistein prevented TNF-α -induced NF-ΚB translocation as well as phosphorylation of IΚB kinase-α/β and IΚBα, and also suppressed TNF-α-induced AMPK inhibition. The production of IL-1β, IL-6, and IL-8 induced by TNF-α was decreased by the phosphatidylinositol-3 kinase inhibitor LY294002, suggesting that inhibition of Akt activation might

  12. Combined B- and T-cell deficiency does not protect against obesity-induced glucose intolerance and inflammation

    NARCIS (Netherlands)

    Ballak, D.B.; Stienstra, R.; Hijmans, A.G.M.; Joosten, L.A.B.; Netea, M.G.; Tack, C.J.J.

    2013-01-01

    Obesity-induced inflammation is associated with insulin resistance and morphologically characterized by macrophage influx into the adipose tissue. Recently, various other immune cells, including B- and T-cells, have been shown to participate in modulating adipose tissue inflammation during the devel

  13. Programmed cell death and its role in inflammation

    Institute of Scientific and Technical Information of China (English)

    Yong Yang; Ge-Ning Jiang; Peng Zhang; Jie Fan

    2015-01-01

    Cell death plays an important role in the regulation of inflammation and may be the result of inflammation. The maintenance of tissue homeostasis necessitates both the recognition and removal of invading microbial pathogens as well as the clearance of dying cells. In the past few decades, emerging knowledge on cell death and inflammation has enriched our molecular understanding of the signaling pathways that mediate various programs of cell death and multiple types of inflammatory responses. This review provides an overview of the major types of cell death related to inflammation. Modification of cell death pathways is likely to be a logical therapeutic target for inflammatory diseases.

  14. Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells.

    Science.gov (United States)

    Dai, Chongshan; Li, Bin; Zhou, Yan; Li, Daowen; Zhang, Shen; Li, Hui; Xiao, Xilong; Tang, Shusheng

    2016-09-01

    The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress, mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor -kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX, a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway. PMID:27375190

  15. Activation of the Retinoid X Receptor Modulates Angiotensin II-Induced Smooth Muscle Gene Expression and Inflammation in Vascular Smooth Muscle Cells

    OpenAIRE

    Lehman, Allison M.B.; Montford, John R.; Horita, Henrick; Ostriker, Allison C.; Weiser-Evans, Mary C. M.; Nemenoff, Raphael A.; Furgeson, Seth B.

    2014-01-01

    The retinoid X receptor (RXR) partners with numerous nuclear receptors, such as the peroxisome proliferator activated receptor (PPAR) family, liver X receptors (LXRs), and farnesoid X receptor (FXR). Although each heterodimer can be activated by specific ligands, a subset of these receptors, defined as permissive nuclear receptors, can also be activated by RXR agonists known as rexinoids. Many individual RXR heterodimers have beneficial effects in vascular smooth muscle cells (SMCs). Because ...

  16. Role of T-Cell Polarization and Inflammation and Their Modulation by n-3 Fatty Acids in Gestational Diabetes and Macrosomia

    Directory of Open Access Journals (Sweden)

    A. Hichami

    2016-01-01

    Full Text Available Th (T helper cells are differentiated into either Th1 or Th2 phenotype. It is generally considered that Th1 phenotype is proinflammatory, whereas Th2 phenotype exerts anti-inflammatory or protective effects. Gestational diabetes mellitus (GDM has been associated with a decreased Th1 phenotype, whereas macrosomia is marked with high expression of Th1 cytokines. Besides, these two pathological situations are marked with high concentrations of inflammatory mediators like tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6, known to play a pivotal role in insulin resistance. Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs may exert a beneficial effect by shifting Th1/Th2 balance to a Th2 phenotype and increasing insulin sensitivity. In this paper, we shed light on the role of T-cell malfunction that leads to an inflammatory and pathophysiological state, related to insulin resistance in GDM and macrosomia. We will also discuss the nutritional management of these pathologies by dietary n-3 polyunsaturated fatty acids (PUFAs.

  17. Role of T-Cell Polarization and Inflammation and Their Modulation by n-3 Fatty Acids in Gestational Diabetes and Macrosomia.

    Science.gov (United States)

    Hichami, A; Grissa, O; Mrizak, I; Benammar, C; Khan, N A

    2016-01-01

    Th (T helper) cells are differentiated into either Th1 or Th2 phenotype. It is generally considered that Th1 phenotype is proinflammatory, whereas Th2 phenotype exerts anti-inflammatory or protective effects. Gestational diabetes mellitus (GDM) has been associated with a decreased Th1 phenotype, whereas macrosomia is marked with high expression of Th1 cytokines. Besides, these two pathological situations are marked with high concentrations of inflammatory mediators like tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), known to play a pivotal role in insulin resistance. Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) may exert a beneficial effect by shifting Th1/Th2 balance to a Th2 phenotype and increasing insulin sensitivity. In this paper, we shed light on the role of T-cell malfunction that leads to an inflammatory and pathophysiological state, related to insulin resistance in GDM and macrosomia. We will also discuss the nutritional management of these pathologies by dietary n-3 polyunsaturated fatty acids (PUFAs). PMID:27313878

  18. Solar cell module. Taiyo denchi module

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Akihiko.

    1990-01-24

    This invention concerns a module frame of solar cell and a solar cell module using this frame. In particular, it concerns a frame and a module useful for the CdS/CdTe or CdS/CuInSe {sub 2} based cell. In the existing solar cell module, sealant is packed in between the edges of a glass substrate, a resin layer and a back protective thin film, etc. and a grooved frame of U-shaped section. For the sealant, silicon based resin and butyl rubber based resin are used many times, but either resin has defects such as their overflow from the module structure. In order to solve these defects, this invention proposes to provide stair-shaped protrusions along the four sides of the bottom of the box frame (herein after called the lower frame) of the module and at the same time, provide a groove for pooling the sealant at the portion where such protrusion meets the side wall, furthermore to provide depressions for pooling the sealant at the upper edge inside the side wall of the lower frame or to punch holes at the corners of the bottom of the lower frame. 9 figs.

  19. Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis

    Directory of Open Access Journals (Sweden)

    Takayuki Okamoto

    2012-01-01

    Full Text Available Deregulated interplay between inflammation and coagulation plays a pivotal role in the pathogenesis of sepsis. Therapeutic approaches that simultaneously target both inflammation and coagulation hold great promise for the treatment of sepsis. Thrombomodulin is an endogenous anticoagulant protein that, in cooperation with protein C and thrombin-activatable fibrinolysis inhibitor, serves to maintain the endothelial microenvironment in an anti-inflammatory and anticoagulant state. A recombinant soluble form of thrombomodulin has been approved to treat patients suffering from disseminated intravascular coagulation (DIC and has thus far shown greater therapeutic potential than heparin. A phase II clinical trial is currently underway in the USA to study the efficacy of thrombomodulin for the treatment of sepsis with DIC complications. This paper focuses on the critical roles that thrombomodulin plays at the intersection of inflammation and coagulation and proposes the possible existence of interactions with integrins via protein C. Finally, we provide a rationale for the clinical application of thrombomodulin for alleviating sepsis.

  20. Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling.

    Science.gov (United States)

    Ma, Yuan; Ge, Ai; Zhu, Wen; Liu, Ya-Nan; Ji, Ning-Fei; Zha, Wang-Jian; Zhang, Jia-Xiang; Zeng, Xiao-Ning; Huang, Mao

    2016-01-01

    Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation. In vivo, ovalbumin- (OVA-) sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay. In vitro, human bronchial epithelial cells (BECs) were challenged by tumor necrosis factor alpha (TNF-α). The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK) evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL-) 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2',7'-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were abolished by morin

  1. Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling

    Directory of Open Access Journals (Sweden)

    Yuan Ma

    2016-01-01

    Full Text Available Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation. In vivo, ovalbumin- (OVA- sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay. In vitro, human bronchial epithelial cells (BECs were challenged by tumor necrosis factor alpha (TNF-α. The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS/mitogen-activated protein kinase (MAPK evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL- 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2′,7′-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were

  2. Sirtinol treatment reduces inflammation in human dermal microvascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Angela Orecchia

    Full Text Available Histone deacetylases (HDAC are key enzymes in the epigenetic control of gene expression. Recently, inhibitors of class I and class II HDAC have been successfully employed for the treatment of different inflammatory diseases such as rheumatoid arthritis, colitis, airway inflammation and asthma. So far, little is known so far about a similar therapeutic effect of inhibitors specifically directed against sirtuins, the class III HDAC. In this study, we investigated the expression and localization of endogenous sirtuins in primary human dermal microvascular endothelial cells (HDMEC, a cell type playing a key role in the development and maintenance of skin inflammation. We then examined the biological activity of sirtinol, a specific sirtuin inhibitor, in HDMEC response to pro-inflammatory cytokines. We found that, even though sirtinol treatment alone affected only long-term cell proliferation, it diminishes HDMEC inflammatory responses to tumor necrosis factor (TNFα and interleukin (IL-1β. In fact, sirtinol significantly reduced membrane expression of adhesion molecules in TNFã- or IL-1β-stimulated cells, as well as the amount of CXCL10 and CCL2 released by HDMEC following TNFα treatment. Notably, sirtinol drastically decreased monocyte adhesion on activated HDMEC. Using selective inhibitors for Sirt1 and Sirt2, we showed a predominant involvement of Sirt1 inhibition in the modulation of adhesion molecule expression and monocyte adhesion on activated HDMEC. Finally, we demonstrated the in vivo expression of Sirt1 in the dermal vessels of normal and psoriatic skin. Altogether, these findings indicated that sirtuins may represent a promising therapeutic target for the treatment of inflammatory skin diseases characterized by a prominent microvessel involvement.

  3. Thymoquinone Alleviates the Experimental Diabetic Peripheral Neuropathy by Modulation of Inflammation.

    Science.gov (United States)

    Chen, Long; Li, Bing; Chen, Biqin; Shao, Yiye; Luo, Qiong; Shi, Xiaohong; Chen, Yinghui

    2016-01-01

    Thymoquinone has been reported to exhibit antioxidant and anti-inflammatory effects. Inflammation plays an important role in pathogenesis of diabetic peripheral neuropathy. This study investigated the effects of TQ on proliferation and apoptosis of Schwann cells exposed to high glucose conditions and electrophysiological and morphological changes of the sciatic nerve in a DPN rat model as well as relevant inflammatory mechanism. Cell proliferation and apoptosis of Schwann cells were measured using the Cell Counting Kit-8 and flow cytometry. DPN model was established in streptozotocin-induced diabetic rats. Nerve conduction velocity was measured before and after treatment. Morphologic changes were observed by H&E staining and transmission electron microscopy. COX-2, IL-1β, IL-6, and Caspase-3 expression was investigated by western blotting and Bio-Plex Pro(TM) Assays. Finally, TQ alleviated the inhibition of Schwann cell proliferation and protected against Schwann cell apoptosis. It improved nerve conduction velocity, and alleviated the DPN-induced morphological changes and demyelination of the sciatic nerve. COX-2, IL-1β, IL-6 and Caspase-3 expression in sciatic nerve or isolated cultured Schwann cells, were also decreased by TQ. These results indicate TQ has a protective effect on peripheral nerves in a DPN rat model. The mechanism may be mediated partly by the modulation of the inflammatory reaction. PMID:27545310

  4. High fat diet and inflammation - modulation of Haptoglobin level in rat brain

    Directory of Open Access Journals (Sweden)

    Maria Stefania eSpagnuolo

    2015-12-01

    Full Text Available Obesity and dietary fats are well known risk factors for the pathogenesis of neurodegenerative diseases. The analysis of specific markers, whose brain level can be affected by diet, might contribute to unveil the intersection between inflammation/obesity and neurodegeneration. Haptoglobin (Hpt is an acute phase protein, which acts as antioxidant by binding free Haemoglobin (Hb, thus neutralizing its pro-oxidative action. We previously demonstrated that Hpt plays critical functions in brain, modulating cholesterol trafficking in neuroblastoma cell lines, beta-amyloid (Aβ uptake by astrocyte, and limiting Aβ toxicity on these cells. A major aim of this study was to evaluate whether a long term (12 or 24 weeks high-fat diet (HFD influences Hpt and Hb expression in rat hippocampus. We also assessed the development of obesity-induced inflammation by measuring hippocampal level of TNF-alpha, and the extent of protein oxidation by titrating nitro-tyrosine (N-Tyr. Hpt concentration was lower (p<0.001 in hippocampus of HFD rats than in control animals, both in the 12 and in the 24 weeks fed groups. HFD was also associated in hippocampus with the increase of Hb level (p<0.01, inflammation and protein oxidative modification, as evidenced by the increase in the concentration of TNF-alpha and nitro-tyrosine. In fact, TNF-alpha concentration was higher in rats receiving HFD for 12 (p<0.01 or 24 weeks (p<0.001 compared to those receiving the control diet. N-Tyr concentration was more elevated in hippocampus of HFD than in control rats in both 12 weeks (p=0.04 and 24 weeks groups (p=0.01, and a positive correlation between Hb and N-Tyr concentration was found in each group. Finally, we found that the treatment of the human glioblastoma-astrocytoma cell line U-87 MG with cholesterol and fatty acids, such as palmitic and linoleic acid, significantly impairs (p<0.001 Hpt secretion in the extracellular compartment.We hypothesize that the HFD-dependent decrease of

  5. Plant-derived modulators of inflammation and cartilage metabolism

    OpenAIRE

    Hougee, S.

    2008-01-01

    Currently the treatment of chronic inflammatory diseases is aimed at inhibiting the symptoms of the disease since there are no curative or preventive treatments available. Rheumatoid arthritis (RA) is a painful chronic inflammatory disease of the joints. Osteoarthritis (OA) is a disease in which pain and inflammation of the joint in certain (end-) stages of the disease plays an important role. For variable reasons patients use natural products to relieve their symptoms, with many claims that ...

  6. Bupleurum polysaccharides attenuates lipopolysaccharide-induced inflammation via modulating Toll-like receptor 4 signaling.

    Directory of Open Access Journals (Sweden)

    Jian Wu

    Full Text Available BACKGROUND: Bupleurum polysaccharides (BPs, isolated from Bupleurum smithii var. parvifolium, possesses immunomodulatory activity, particularly on inflammation. Bacterial endotoxin lipopolysaccharide (LPS triggers innate immune responses through Toll-like receptor 4 (TLR4 on host cell membrane. The present study was performed to evaluate whether the therapeutic efficacy of BPs on suppression of LPS's pathogenecity could be associated with the modulating of TLR4 signaling pathway. METHODOLOGY/PRINCIPAL FINDINGS: LPS stimulated expression and activation of factors in the TLR4 signaling system, including TLR4, CD14, IRAK4, TRAF6, NF-κB, and JNK, determined using immunocytochemical and/or Western blot assays. BPs significantly inhibited these effects of LPS. LPS increased pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12p40, and IFN-β and NO production, evaluated using ELISA and Griess reaction assays, respectively. BPs antagonized these effects of LPS. Interestingly, BPs alone augmented secretion of some pro-inflammatory cytokines of non-LPS stimulated macrophages and enhanced phagocytic activity towards fluorescent E.coli bioparticles. In a rat model of acute lung injury (ALI with pulmonary hemorrhage and inflammation, BPs ameliorated lung injuries and suppressed TLR4 expression. SIGNIFICANCE: The therapeutic properties of BPs in alleviating inflammatory diseases could be attributed to its inhibitory effect on LPS-mediated TLR4 signaling.

  7. Reactive Bone Marrow Stromal Cells Attenuate Systemic Inflammation via sTNFR1

    OpenAIRE

    Yagi, Hiroshi; Soto-Gutierrez, Alejandro; Navarro-Alvarez, Nalu; Nahmias, Yaakov; Goldwasser, Yoni; Kitagawa, Yuko; Tilles, Arno W.; Tompkins, Ronald G.; Parekkadan, Biju; Yarmush, Martin L

    2010-01-01

    Excessive systemic inflammation following trauma, sepsis, or burn could lead to distant organ damage. The transplantation of bone marrow stromal cells or mesenchymal stem cells (MSCs) has been reported to be an effective treatment for several immune disorders by modulating the inflammatory response to injury. We hypothesized that MSCs can dynamically secrete systemic factors that can neutralize the activity of inflammatory cytokines. In this study, we showed that cocultured MSCs are able to d...

  8. Solar cell module. Taiyo denchi module

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Akihiko; Matsumoto, Hitoshi; Komatsu, Yasumitsu; Shirai, Sadaharu.

    1989-09-29

    In the solar cell module of this invention, such junctions as CdS/CdTe or CdS/CuInSe {sub 2} are contained as a photoelectromotive force part coexists with air in a closed space which consists of glass, metal parts and a bonding resin layer; the photoelectromotive force part is coated either with a fluorine resin or a silicone resin. The fluorine resin contains a fundamental skeleton of an alternative copolymer of fluoroolefin and a hydrocarbon-based vinyl monomer; the silicone resin has three types, i.e., addition-reacted, condensated or UV-curing type, and the released oxygen is sealed in the closed space. The resin layer which adheres the glass and the metal plate is a thermoplastic resin which is polyethylene modified by copolymerization of acid anhydride. By this, the reliability of the solar cell module was enhanced. 3 figs.

  9. Helminth Parasites and the Modulation of Joint Inflammation

    Directory of Open Access Journals (Sweden)

    Chelsea E. Matisz

    2011-01-01

    Full Text Available There is an urgent need to develop better therapeutics for autoimmune and autoinflammatory diseases, of which musculoskeletal disorders such as rheumatoid arthritis are particularly prevalent and debilitating. Helminth parasites are accomplished masters at modifying their hosts' immune activity, and so attention has focused on rodent-helminth model systems to uncover the workings of the mammalian immune response to metazoan parasites, with the hope of revealing molecules and/or mechanisms that can be translated into better treatments for human autoimmune and idiopathic disorders. Substantial proof-of-principal data supporting the concept that infection with helminth parasites can reduce the severity of concomitant disease has been amassed from models of mucosal inflammation. Indeed, infection with helminth parasites has been tried as a therapy in inflammatory bowel disease, and there are case reports relating to other conditions (e.g., autism; however, the impact of infection with parasitic helminths on musculoskeletal diseases has not been extensively studied. Here, we present the view that such a strategy should be applied to the amelioration of joint inflammation and review the literature that supports this contention.

  10. Caffeine Intake May Modulate Inflammation Markers in Trained Rats

    Directory of Open Access Journals (Sweden)

    Rômulo Pillon Barcelos

    2014-04-01

    Full Text Available Caffeine is presented in many commercial products and has been proven to induce ergogenic effects in exercise, mainly related to redox status homeostasis, inflammation and oxidative stress-related adaptation mechanisms. However, most studies have mainly focused on muscle adaptations, and the role of caffeine in different tissues during exercise training has not been fully described. The aim of this study was therefore, to analyze the effects of chronic caffeine intake and exercise training on liver mitochondria functioning and plasma inflammation markers. Rats were divided into control, control/caffeine, exercise, and exercise/caffeine groups. Exercise groups underwent four weeks of swimming training and caffeine groups were supplemented with 6 mg/kg/day. Liver mitochondrial swelling and complex I activity, and plasma myeloperoxidase (MPO and acetylcholinesterase (AChE activities were measured. An anti-inflammatory effect of exercise was evidenced by reduced plasma MPO activity. Additionally, caffeine intake alone and combined with exercise decreased the plasma AChE and MPO activities. The per se anti-inflammatory effect of caffeine intake should be highlighted considering its widespread use as an ergogenic aid. Therefore, caffeine seems to interfere on exercise-induced adaptations and could also be used in different exercise-related health treatments.

  11. Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation; Caracterisation et modulation pharmacologique de l'inflammation intestinale induite par les rayonnements ionisants

    Energy Technology Data Exchange (ETDEWEB)

    Gremy, O

    2006-12-15

    The use of radiation therapy to treat abdominal and pelvic malignancies inevitably involves exposure of healthy intestinal tissues which are very radiosensitive. As a result, most patients experience symptoms such as abdominal pain, nausea and diarrhea. Such symptoms are associated with acute damage to intestine mucosa including radio-induced inflammatory processes. With a rat model of colorectal fractionated radiation, we have shown a gradual development of a colonic inflammation during radiation planning, without evident tissue injury. This radio-induced inflammation is characterized not only by the sur expressions of pro-inflammatory cytokines and chemokines, a NF-kB activation, but also by a repression of anti-inflammatory cytokines and the nuclear receptors PPARa and RXRa, both involved in inflammation control. This early inflammation is associated with a discreet neutrophil recruitment and a macrophage accumulation. Macrophages are still abnormally numerous in tissue 27 weeks after the last day of irradiation. Inflammatory process is the most often related to a specific immune profile, either a type Th1 leading to a cellular immune response, or a type Th2 for humoral immunity. According to our studies, a unique abdominal radiation in the rat induces an ileum inflammation and an immune imbalance resulting in a Th2-type profile. Inhibiting this profile is important as its persistence promotes chronic inflammation, predisposition to bacterial infections and fibrosis which is the main delayed side-effect of radiotherapy. The treatment of rats with an immuno-modulator compound, the caffeic acid phenethyl ester (C.A.P.E.), have the potential to both reduce ileal mucosal inflammation and inhibit the radio-induced Th2 status. In order to search new therapeutic molecular target, we has been interested in the PPARg nuclear receptor involved in the maintenance of colon mucosal integrity. In our abdominal irradiation model, we have demonstrated that the prophylactic

  12. Modulation of airway inflammation to prevent exacerbations of COPD

    Directory of Open Access Journals (Sweden)

    M. Solèr

    2005-12-01

    Full Text Available Exacerbations of chronic obstructive pulmonary disease (COPD are periods in the chronic course of this disease with symptoms of intensified inflammation, induced in part by infections but also by noninfectious irritating mechanisms. Although these exacerbations seem to be linked to accelerated long-term disease progression and impaired quality of life, there are only limited preventive measures available, apart from smoking cessation. This article compares the effectiveness of different pharmacological treatments for the prevention of COPD exacerbations, including the oral bacterial lysate OM-85. Given the differences in the mechanism of action of the treatments discussed, this opens some hope for additive or potentiating effects with combined treatments, which will have to be studied in future controlled trials.

  13. Solar cell module. Taiyo denchi module

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Akihiko; Matsumoto, Hitoshi.

    1989-09-06

    In the conventional solar cell module, the cell cost is elevated because the cross sections of the cell edge is surrounded with frames of various shape and the gap is filled with a sealant. In additionn, the top end of the module frame is placed roughly 1 mm above the glass surface; the photoelectromotive force part is covered with such deposits as soils and sands, thus badly affecting the photovoltaic generation. In this invention, weather-proof opaque paint is coated around the surface glass to interrupt the light irradiation to the adhesive resin layer between the glass and the back sheet, thus preventing the degradation of the resin layer. Cost is low because of using a thin film. The light interruption by the deposits can be prevented. The photoelectromotive force element is a n-type CdS film or CdS/CdTe. The resin layer around the glass is a thermoplastic polyolefin which is modified with acid anhydrides. 5 figs.

  14. Allosteric modulation of sigma-1 receptors by SKF83959 inhibits microglia-mediated inflammation.

    Science.gov (United States)

    Wu, Zhuang; Li, Linlang; Zheng, Long-Tai; Xu, Zhihong; Guo, Lin; Zhen, Xuechu

    2015-09-01

    Recent studies have shown that sigma-1 receptor orthodox agonists can inhibit neuroinflammation. SKF83959 (3-methyl-6-chloro-7,8-hydroxy-1-[3-methylphenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine), an atypical dopamine receptor-1 agonist, has been recently identified as a potent allosteric modulator of sigma-1 receptor. Here, we investigated the anti-inflammatory effects of SKF83959 in lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results indicated that SKF83959 significantly suppressed the expression/release of the pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), and inhibited the generation of reactive oxygen species. All of these responses were blocked by selective sigma-1 receptor antagonists (BD1047 or BD1063) and by ketoconazole (an inhibitor of enzyme cytochrome c17 to inhibit the synthesis of endogenous dehydroepiandrosterone, DHEA). Additionally, we found that SKF83959 promoted the binding activity of DHEA with sigma-1 receptors, and enhanced the inhibitory effects of DHEA on LPS-induced microglia activation in a synergic manner. Furthermore, in a microglia-conditioned media system, SKF83959 inhibited the cytotoxicity of conditioned medium generated by LPS-activated microglia toward HT-22 neuroblastoma cells. Taken together, our study provides the first evidence that allosteric modulation of sigma-1 receptors by SKF83959 inhibits microglia-mediated inflammation. SKF83959 is a potent allosteric modulator of sigma-1 receptor. Our results indicated that SKF83959 enhanced the activity of endogenous dehydroepiandrosterone (DHEA) in a synergic manner, and inhibited the activation of BV2 microglia and the expression/release of the pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS).

  15. Cancer and inflammation studies using zebrafish cell lines

    NARCIS (Netherlands)

    He, Shuning

    2010-01-01

    As the zebrafish, Danio rerio, has been increasingly used as an animal model for biomedical research, we aimed to establish zebrafish cell line models for inflammation and cancer studies in this thesis. Several zebrafish cell lines were characterized and their genetic and physiological properties we

  16. Chronic Inflammation and γδ T Cells.

    Science.gov (United States)

    Fay, Nathan S; Larson, Emily C; Jameson, Julie M

    2016-01-01

    The epithelial tissues of the skin, lungs, reproductive tract, and intestines are the largest physical barriers the body has to protect against infection. Epithelial tissues are woven with a matrix of immune cells programed to mobilize the host innate and adaptive immune responses. Included among these immune cells are gamma delta T lymphocytes (γδ T cells) that are unique in their T cell receptor usage, location, and functions in the body. Stress reception by γδ T cells as a result of traumatic epithelial injury, malignancy, and/or infection induces γδ T cell activation. Once activated, γδ T cells function to repair tissue, induce inflammation, recruit leukocytes, and lyse cells. Many of these functions are mediated via the production of cytokines and growth factors upon γδ T cell activation. Pathogenesis of many chronic inflammatory diseases involves γδ T cells; some of which are exacerbated by their presence, while others are improved. γδ T cells require a delicate balance between their need for acute inflammatory mediators to function normally and the detrimental impact imparted by chronic inflammation. This review will focus on the recent progress made in understanding how epithelial γδ T cells influence the pathogenesis of chronic inflammatory diseases and how a balance between acute and chronic inflammation impacts γδ T cell function. Future studies will be important to understand how this balance is achieved. PMID:27303404

  17. Turning Down the Thermostat: Modulating the Endocannabinoid System in Ocular Inflammation and Pain

    Science.gov (United States)

    Toguri, James T.; Caldwell, Meggie; Kelly, Melanie E. M.

    2016-01-01

    The endocannabinoid system (ECS) has emerged as an important regulator of both physiological and pathological processes. Notably, this endogenous system plays a key role in the modulation of pain and inflammation in a number of tissues. The components of the ECS, including endocannabinoids, their cognate enzymes and cannabinoid receptors, are localized in the eye, and evidence indicates that ECS modulation plays a role in ocular disease states. Of these diseases, ocular inflammation presents a significant medical problem, given that current clinical treatments can be ineffective or are associated with intolerable side-effects. Furthermore, a prominent comorbidity of ocular inflammation is pain, including neuropathic pain, for which therapeutic options remain limited. Recent evidence supports the use of drugs targeting the ECS for the treatment of ocular inflammation and pain in animal models; however, the potential for therapeutic use of cannabinoid drugs in the eye has not been thoroughly investigated at this time. This review will highlight evidence from experimental studies identifying components of the ocular ECS and discuss the functional role of the ECS during different ocular inflammatory disease states, including uveitis and corneal keratitis. Candidate ECS targeted therapies will be discussed, drawing on experimental results obtained from both ocular and non-ocular tissue(s), together with their potential application for the treatment of ocular inflammation and pain. PMID:27695415

  18. Transparent solar cell window module

    Energy Technology Data Exchange (ETDEWEB)

    Chau, Joseph Lik Hang; Chen, Ruei-Tang; Hwang, Gan-Lin; Tsai, Ping-Yuan [Nanopowder and Thin Film Technology Center, ITRI South, Industrial Technology Research Institute, Tainan County 709 (China); Lin, Chien-Chu [I-Lai Acrylic Corporation, Tainan City (China)

    2010-03-15

    A transparent solar cell window module based on the integration of traditional silicon solar cells and organic-inorganic nanocomposite material was designed and fabricated. The transparent solar cell window module was composed of a nanocomposite light-guide plate and traditional silicon solar cells. The preparation of the nanocomposite light-guide plate is easy without modification of the traditional casting process, the nanoparticles sol can be added directly to the polymethyl methacrylate (PMMA) monomer syrup during the process. The solar energy collected by this window can be used to power up small household electrical appliances. (author)

  19. Chronic Inflammation and  T Cells

    Directory of Open Access Journals (Sweden)

    Nathan S Fay

    2016-05-01

    Full Text Available The epithelial tissues of the skin, lungs, reproductive tract, and intestines are the largest physical barriers the body has to protect against infection. Epithelial tissues are woven with a matrix of immune cells programmed to mobilize the host innate and adaptive immune responses. Included among these immune cells are  T cells that are unique in their TCR usage, location, and functions in the body. Stress reception by  T cells as a result of traumatic epithelial injury, malignancy, and/or infection induces  T cell activation. Once activated,  T cells function to repair tissue, induce inflammation, recruit leukocytes, and lyse cells. Many of these functions are mediated via the production of cytokines and growth factors upon  T cell activation. Pathogenesis of many chronic inflammatory diseases involve  T cells; some of which are exacerbated by their presence, while others are improved.  T cells require a delicate balance between their need for acute inflammatory mediators to function normally and the detrimental impact imparted by chronic inflammation. This review will focus on the recent progress made in understanding how epithelial  T cells influence the pathogenesis of chronic inflammatory diseases and how a balance between acute and chronic inflammation impacts  T cell function. Future studies will be important to understand how this balance is achieved.

  20. Battery cell module

    Energy Technology Data Exchange (ETDEWEB)

    Shambaugh, J.S.

    1981-11-23

    A modular lithium battery having a plurality of cells, having electrical connecting means connecting the cells to output terminals, and venting means for releasing discharge byproducts to a chemical scrubber is disclosed. Stainless steel cell casings are potted in an aluminum modular case with syntactic foam and epoxy. The wall thickness resulting is about 0.5 inches.

  1. Important role of platelets in modulating endotoxin-induced lung inflammation in CFTR-deficient mice.

    Directory of Open Access Journals (Sweden)

    Caiqi Zhao

    Full Text Available Mutation of CFTR (cystic fibrosis transmembrane conductance regulator leads to cystic fibrosis (CF. Patients with CF develop abnormalities of blood platelets and recurrent lung inflammation. However, whether CFTR-mutated platelets play a role in the development of lung inflammation is elusive. Therefore, we intratracheally challenged wildtype and F508del (a common type of CFTR mutation mice with LPS to observe changes of F508del platelets in the peripheral blood and indexes of lung inflammation (BAL neutrophils and protein levels. Furthermore, we investigated whether or not and how F508del platelets modulate the LPS-induced acute lung inflammation by targeting anti-platelet aggregation, depletion of neutrophils, reconstitution of bone marrow or neutrophils, blockade of P-selectin glycoprotein ligand-1 (PSGL-1, platelet activating factor (PAF, and correction of mutated CFTR trafficking. We found that LPS-challenged F508del mice developed severe thrombocytopenia and had higher levels of plasma TXB2 coincided with neutrophilic lung inflammation relative to wildtype control. Inhibition of F508del platelet aggregation or depletion of F508del neutrophils diminished the LPS-induced lung inflammation in the F508del mice. Moreover, wildtype mice reconstituted with either F508del bone marrow or neutrophils developed worse thrombocytopenia. Blocking PSGL-1, platelet activating factor (PAF, or rectifying trafficking of mutated CFTR in F508del mice diminished and alveolar neutrophil transmigration in the LPS-challenged F508del mice. These findings suggest that F508del platelets and their interaction with neutrophils are requisite for the development of LPS-induced lung inflammation and injury. As such, targeting platelets might be an emerging strategy for dampening recurrent lung inflammation in cystic fibrosis patients.

  2. Extrathymically generated regulatory T cells control mucosal Th2 inflammation

    OpenAIRE

    Josefowicz, Steven Z.; Niec, Rachel E.; Kim, Hye Young; Treuting, Piper; Chinen, Takatoshi; Zheng, Ye; Umetsu, Dale T.; Rudensky, Alexander Y.

    2012-01-01

    A balance between pro- and anti-inflammatory mechanisms at mucosal interfaces, sites of constitutive exposure to microbes and non-microbial foreign substances, allows for efficient protection against pathogens yet prevents adverse inflammatory responses associated with allergy, asthma, and intestinal inflammation1. Regulatory T (Treg) cells prevent systemic and tissue-specific autoimmunity and inflammatory lesions at mucosal interfaces. These cells are generated in the thymus (tTreg cells) an...

  3. Pathogenic memory type Th2 cells in allergic inflammation.

    Science.gov (United States)

    Endo, Yusuke; Hirahara, Kiyoshi; Yagi, Ryoji; Tumes, Damon J; Nakayama, Toshinori

    2014-02-01

    Immunological memory is a hallmark of adaptive immunity. Memory CD4 T helper (Th) cells are central to acquired immunity, and vaccines for infectious diseases are developed based on this concept. However, memory Th cells also play a critical role in the pathogenesis of various chronic inflammatory diseases, including asthma. We refer to these populations as 'pathogenic memory Th cells.' Here, we review recent developments highlighting the functions and characteristics of several pathogenic memory type Th2 cell subsets in allergic inflammation. Also discussed are the similarities and differences between pathogenic memory Th2 cells and recently identified type 2 innate lymphoid cells (ILC2), focusing on cytokine production and phenotypic profiles.

  4. The Inflammation Response to DEHP through PPARγ in Endometrial Cells

    Directory of Open Access Journals (Sweden)

    Qiansheng Huang

    2016-03-01

    Full Text Available Epidemiological studies have shown the possible link between phthalates and endometrium-related gynecological diseases, however the molecular mechanism(s behind this is/are still unclear. In the study, both primary cultured endometrial cells and an endometrial adenocarcinoma cell line (Ishikawa were recruited to investigate the effects of di-(2-ethylhexyl phthalate (DEHP at human-relevant concentrations. The results showed that DEHP did not affect the viability of either type of cell, which showed different responses to inflammation. Primary cultured cells showed stronger inflammatory reactions than the Ishikawa cell line. The expression of inflammatory factors was induced both at the mRNA and protein levels, however the inflammation did not induce the progress of epithelial-mesenchymal transition (EMT as the protein levels of EMT markers were not affected after exposure to either cell type. Further study showed that the mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ wereup-regulated after exposure. In all, our study showed that human-relevant concentrations of DEHP could elicit the inflammatory response in primary cultured endometrial cells rather than in Ishikawa cell line. PPARγ may act as the mediating receptor in the inflammation reaction.

  5. Targeting inflammation with autoantigen-specific T cells

    NARCIS (Netherlands)

    Guichelaar, T.

    2008-01-01

    Chronic autoimmune diseases are driven by cells that respond to tissue components of the body. Inflammation in diseases like rheumatoid arthritis, diabetes or multiple sclerosis, can be suppressed by drug therapy. However, the broad range of immunosuppressive action of these drugs often does not res

  6. Group 2 innate lymphoid cells in lung inflammation

    NARCIS (Netherlands)

    B.W.S. Li (Bobby W.); R.W. Hendriks (Rudi)

    2013-01-01

    textabstractSummary: Although allergic asthma is a heterogeneous disease, allergen-specific T helper 2 (Th2) cells producing the key cytokines involved in type 2 inflammation, interleukin-4 (IL-4), IL-5 and IL-13, are thought to play a major role in asthma pathogenesis. This model is challenged by t

  7. Control of Th2-Mediated Inflammation by Regulatory T Cells

    OpenAIRE

    Poojary, K. Venuprasad; Kong, Yi-chi M.; Farrar, Michael A.

    2010-01-01

    Allergic diseases and asthma are caused by dysregulated Th2-type immune responses, which drive disease development in susceptible individuals. Immune tolerance to allergens prevents inflammatory symptoms in the respiratory mucosa and provides protection against inflammation in the airways. Increasing evidence indicates that Foxp3+ regulatory T cells (Tregs) play a critical role in immune tolerance and control Th2-biased responses. Tregs develop in the thymus from CD4+ T cells (natural Tregs) ...

  8. Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation

    International Nuclear Information System (INIS)

    The use of radiation therapy to treat abdominal and pelvic malignancies inevitably involves exposure of healthy intestinal tissues which are very radiosensitive. As a result, most patients experience symptoms such as abdominal pain, nausea and diarrhea. Such symptoms are associated with acute damage to intestine mucosa including radio-induced inflammatory processes. With a rat model of colorectal fractionated radiation, we have shown a gradual development of a colonic inflammation during radiation planning, without evident tissue injury. This radio-induced inflammation is characterized not only by the sur expressions of pro-inflammatory cytokines and chemokines, a NF-kB activation, but also by a repression of anti-inflammatory cytokines and the nuclear receptors PPARa and RXRa, both involved in inflammation control. This early inflammation is associated with a discreet neutrophil recruitment and a macrophage accumulation. Macrophages are still abnormally numerous in tissue 27 weeks after the last day of irradiation. Inflammatory process is the most often related to a specific immune profile, either a type Th1 leading to a cellular immune response, or a type Th2 for humoral immunity. According to our studies, a unique abdominal radiation in the rat induces an ileum inflammation and an immune imbalance resulting in a Th2-type profile. Inhibiting this profile is important as its persistence promotes chronic inflammation, predisposition to bacterial infections and fibrosis which is the main delayed side-effect of radiotherapy. The treatment of rats with an immuno-modulator compound, the caffeic acid phenethyl ester (C.A.P.E.), have the potential to both reduce ileal mucosal inflammation and inhibit the radio-induced Th2 status. In order to search new therapeutic molecular target, we has been interested in the PPARg nuclear receptor involved in the maintenance of colon mucosal integrity. In our abdominal irradiation model, we have demonstrated that the prophylactic

  9. Transcription factor network downstream of protease activated receptors (PARs modulating mouse bladder inflammation

    Directory of Open Access Journals (Sweden)

    Hurst Robert E

    2007-08-01

    Full Text Available Abstract Background All four PARs are present in the urinary bladder, and their expression is altered during inflammation. In order to search for therapeutic targets other than the receptors themselves, we set forth to determine TFs downstream of PAR activation in the C57BL/6 urinary bladders. Methods For this purpose, we used a protein/DNA combo array containing 345 different TF consensus sequences. Next, the TF selected was validated by EMSA and IHC. As mast cells seem to play a fundamental role in bladder inflammation, we determined whether c-kit receptor deficient (Kitw/Kitw-v mice have an abrogated response to PAR stimulation. Finally, TFEB antibody was used for CHIP/Q-PCR assay and revealed up-regulation of genes known to be downstream of TFEB. Results TFEB, a member of the MiTF family of basic helix-loop-helix leucine zipper, was the only TF commonly up-regulated by all PAR-APs. IHC results confirm a correlation between inflammation and TFEB expression in C57BL/6 mice. In contrast, Kitw/Kitw-v mice did not exhibit inflammation in response to PAR activation. EMSA results confirmed the increased TFEB binding activity in C57BL/6 but not in Kitw/Kitw-v mice. Conclusion This is the first report describing the increased expression of TFEB in bladder inflammation in response to PAR activation. As TFEB belongs to a family of TFs essential for mast cell survival, our findings suggest that this molecule may influence the participation of mast cells in PAR-mediated inflammation and that targeting TFEB/MiTF activity may be a novel approach for the treatment of bladder inflammatory disorders.

  10. Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation

    OpenAIRE

    Mills, Kingston; Raverdeau, Mathilde

    2013-01-01

    PUBLISHED Retinoic acid (RA), a vitamin A metabolite, modulates mucosal T helper cell responses. Here we examined the role of RA in regulating IL-22 production by γδ T cells and innate lymphoid cells in intestinal inflammation. RA significantly enhanced IL-22 production by γδ T cells stimulated in vitro with IL-1β or IL-18 and IL-23. In vivo RA attenuated colon inflammation induced by dextran sodium sulfate treatment or Citrobacter rodentium infection. This was associated with a significan...

  11. Inflammation after Ischemic Stroke: The Role of Leukocytes and Glial Cells

    Science.gov (United States)

    Kim, Jong Youl; Park, Joohyun; Chang, Ji Young; Kim, Sa-Hyun

    2016-01-01

    The immune response after stroke is known to play a major role in ischemic brain pathobiology. The inflammatory signals released by immune mediators activated by brain injury sets off a complex series of biochemical and molecular events which have been increasingly recognized as a key contributor to neuronal cell death. The primary immune mediators involved are glial cells and infiltrating leukocytes, including neutrophils, monocytes and lymphocyte. After ischemic stroke, activation of glial cells and subsequent release of pro- and anti-inflammatory signals are important for modulating both neuronal cell damage and wound healing. Infiltrated leukocytes release inflammatory mediators into the site of the lesion, thereby exacerbating brain injury. This review describes how the roles of glial cells and circulating leukocytes are a double-edged sword for neuroinflammation by focusing on their detrimental and protective effects in ischemic stroke. Here, we will focus on underlying characterize of glial cells and leukocytes under inflammation after ischemic stroke.

  12. Sterile inflammation - do innate lymphoid cell subsets play a role?

    OpenAIRE

    Walsh, Patrick

    2012-01-01

    PUBLISHED The recent identification of several novel innate lymphoid cell (iLC) subsets has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets toward the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent st...

  13. Human primary adipocytes exhibit immune cell function: adipocytes prime inflammation independent of macrophages.

    Directory of Open Access Journals (Sweden)

    Kees Meijer

    Full Text Available BACKGROUND: Obesity promotes inflammation in adipose tissue (AT and this is implicated in pathophysiological complications such as insulin resistance, type 2 diabetes and cardiovascular disease. Although based on the classical hypothesis, necrotic AT adipocytes (ATA in obese state activate AT macrophages (ATM that then lead to a sustained chronic inflammation in AT, the link between human adipocytes and the source of inflammation in AT has not been in-depth and systematically studied. So we decided as a new hypothesis to investigate human primary adipocytes alone to see whether they are able to prime inflammation in AT. METHODS AND RESULTS: Using mRNA expression, human preadipocytes and adipocytes express the cytokines/chemokines and their receptors, MHC II molecule genes and 14 acute phase reactants including C-reactive protein. Using multiplex ELISA revealed the expression of 50 cytokine/chemokine proteins by human adipocytes. Upon lipopolysaccharide stimulation, most of these adipocyte-associated cytokines/chemokines and immune cell modulating receptors were up-regulated and a few down-regulated such as (ICAM-1, VCAM-1, MCP-1, IP-10, IL-6, IL-8, TNF-α and TNF-β highly up-regulated and IL-2, IL-7, IL-10, IL-13 and VEGF down-regulated. In migration assay, human adipocyte-derived chemokines attracted significantly more CD4+ T cells than controls and the number of migrated CD4+ cells was doubled after treating the adipocytes with LPS. Neutralizing MCP-1 effect produced by adipocytes reduced CD4+ migration by approximately 30%. CONCLUSION: Human adipocytes express many cytokines/chemokines that are biologically functional. They are able to induce inflammation and activate CD4+ cells independent of macrophages. This suggests that the primary event in the sequence leading to chronic inflammation in AT is metabolic dysfunction in adipocytes, followed by production of immunological mediators by these adipocytes, which is then exacerbated by

  14. Role of Inflammation and Substrate Stiffness in Cancer Cell Transmigration

    Science.gov (United States)

    Hamilla, Susan; Stroka, Kimberly; Aranda-Espinoza, Helim

    2013-03-01

    Cancer metastasis, the ability for cancer cells to break away from the primary tumor site and spread to other organs of the body, is one of the main contributing factors to the deadliness of the disease. One of the rate-limiting steps in cancer metastasis that is not well understood is the adhesion of tumor cells to the endothelium followed by transmigration. Other factors include substrate stiffness and inflammation. To test these parameters, we designed an in vitro model of transendothelial migration. Our results suggest that cancer cell transmigration is a two-step process in which they first incorporate into the endothelium before migrating through. It was observed that the cumulative fraction of cancer cells that incorporate into the endothelium increases over time. Unlike leukocytes, which can directly transmigrate through the endothelium, cancer cells appear to have a two-step process of transmigration. Our results indicate that inflammation does not act as a signal for cancer cells to localize at specific sites and transmigrate similarly to leukocytes. Cancer cell transmigration also does not vary with substrate stiffness indicating that tissue stiffness may not play a role in cancer's propensity to metastasize to certain tissues.

  15. Serum Amyloid A Induces Inflammation, Proliferation and Cell Death in Activated Hepatic Stellate Cells.

    Science.gov (United States)

    Siegmund, Sören V; Schlosser, Monika; Schildberg, Frank A; Seki, Ekihiro; De Minicis, Samuele; Uchinami, Hiroshi; Kuntzen, Christian; Knolle, Percy A; Strassburg, Christian P; Schwabe, Robert F

    2016-01-01

    Serum amyloid A (SAA) is an evolutionary highly conserved acute phase protein that is predominantly secreted by hepatocytes. However, its role in liver injury and fibrogenesis has not been elucidated so far. In this study, we determined the effects of SAA on hepatic stellate cells (HSCs), the main fibrogenic cell type of the liver. Serum amyloid A potently activated IκB kinase, c-Jun N-terminal kinase (JNK), Erk and Akt and enhanced NF-κB-dependent luciferase activity in primary human and rat HSCs. Serum amyloid A induced the transcription of MCP-1, RANTES and MMP9 in an NF-κB- and JNK-dependent manner. Blockade of NF-κB revealed cytotoxic effects of SAA in primary HSCs with signs of apoptosis such as caspase 3 and PARP cleavage and Annexin V staining. Serum amyloid A induced HSC proliferation, which depended on JNK, Erk and Akt activity. In primary hepatocytes, SAA also activated MAP kinases, but did not induce relevant cell death after NF-κB inhibition. In two models of hepatic fibrogenesis, CCl4 treatment and bile duct ligation, hepatic mRNA levels of SAA1 and SAA3 were strongly increased. In conclusion, SAA may modulate fibrogenic responses in the liver in a positive and negative fashion by inducing inflammation, proliferation and cell death in HSCs. PMID:26937641

  16. Scavenger receptor CD36 expression contributes to adipose tissue inflammation and cell death in diet-induced obesity.

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    Lei Cai

    Full Text Available OBJECTIVE: The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death. EXPERIMENTAL APPROACH: Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO mice and wild type (WT mice fed a high fat diet (60% kcal fat for 16 weeks and the inflammatory response was studied in primary adipocytes and macrophages isolated from CD36 KO and WT mice. RESULTS: Compared to WT mice, CD36 KO mice fed a high fat diet exhibited reduced adiposity and adipose tissue inflammation, with decreased adipocyte cell death, pro-inflammatory cytokine expression and macrophage and T-cell accumulation. In primary cell culture, the absence of CD36 expression in macrophages decreased pro-inflammatory cytokine, pro-apoptotic and ER stress gene expression in response to lipopolysaccharide (LPS. Likewise, CD36 deficiency in primary adipocytes reduced pro-inflammatory cytokine and chemokine secretion in response to LPS. Primary macrophage and adipocyte co-culture experiments showed that these cell types act synergistically in their inflammatory response to LPS and that CD36 modulates such synergistic effects. CONCLUSIONS: CD36 enhances adipose tissue inflammation and cell death in diet-induced obesity through its expression in both macrophages and adipocytes.

  17. Estrogen signaling modulates allergic inflammation and contributes to sex differences in asthma.

    Directory of Open Access Journals (Sweden)

    Aleksander eKeselman

    2015-11-01

    Full Text Available Asthma is a chronic airway inflammatory disease that afflicts approximately 300 million people worldwide. It is characterized by airway constriction that leads to wheezing, coughing, and shortness of breath. The most common treatments are corticosteroids and β2-adrenergic receptor antagonists, which target inflammation and airway smooth muscle constriction, respectively. The incidence and severity of asthma is greater in women than in men, and women are more prone to develop corticosteroid-resistant or hard-to-treat asthma. Puberty, menstruation, pregnancy, menopause, and oral contraceptives are known to contribute to disease outcome in women, potentially suggesting a role for estrogen and other hormones impacting allergic inflammation. Currently, the mechanisms underlying these sex differences are poorly understood, although the effect of sex hormones, such as estrogen, on allergic inflammation is gaining interest. Asthma presents as a heterogeneous disease. In typical Th2-type allergic asthma, interleukin-4 and interleukin-13 predominate, driving IgE production and recruitment of eosinophils into the lungs. Chronic Th2-inflammation in the lung results in structural changes and activation of multiple immune cell types, leading to a deterioration of lung function over time. Most immune cells express estrogen receptors (ERα, ERβ, or the membrane-bound G-protein-coupled estrogen receptor to varying degrees and can respond to the hormone. Together these receptors have demonstrated the capacity to regulate a spectrum of immune functions, including adhesion, migration, survival, wound healing, and antibody and cytokine production. This review will cover the current understanding of estrogen signaling in allergic inflammation and discuss how this signaling may contribute to sex differences in asthma and allergy.

  18. Coincident helminth infection modulates systemic inflammation and immune activation in active pulmonary tuberculosis.

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    Parakkal Jovvian George

    Full Text Available Helminth infections are known to modulate innate and adaptive immune responses in active and latent tuberculosis (TB. However, the role of helminth infections in modulating responses associated with inflammation and immune activation (reflecting disease activity and/or severity in TB is not known.We measured markers of inflammation and immune activation in active pulmonary TB individuals (ATB with co-incidental Strongyloides stercoralis (Ss infection. These included systemic levels of acute phase proteins, matrix metalloproteinases and their endogenous inhibitors and immune activation markers. As a control, we measured the systemic levels of the same molecules in TB-uninfected individuals (NTB with or without Ss infection.Our data confirm that ATB is associated with elevated levels of the various measured molecules when compared to those seen in NTB. Our data also reveal that co-incident Ss infection in ATB individuals is associated with significantly decreased circulating levels of acute phase proteins, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases as well as the systemic immune activation markers, sCD14 and sCD163. These changes are specific to ATB since they are absent in NTB individuals with Ss infection.Our data therefore reveal a profound effect of Ss infection on the markers associated with TB disease activity and severity and indicate that co-incidental helminth infections might dampen the severity of TB disease.

  19. Montelukast modulates lung CysLT1 receptor expression and eosinophilic inflammation in asthmatic mice

    Institute of Scientific and Technical Information of China (English)

    Yan-jun ZHANG; Lei ZHANG; Shao-bin WANG; Hua-hao SHEN; Er-qing WEI

    2004-01-01

    AIM: To determine the expressions of cysteinyl leukotriene receptors, CysLT1 and CysLT2, in airway eosinophilic inflammation of OVA-induced asthmatic mice and the modulation by montelukast, a CysLT1 receptor antagonist.METHODS: Asthma model was induced by chronic exposure to ovalbumin (OVA) in C57BL/6 mice. The eosinophils in bronchoalveolar lavage (BAL) fluid and lung tissues were counted, IL-5 level in BAL fluid was measured,and CysLT1 and CysLT2 receptor mRNA expressions were detected by semi-quantitative RT-PCR. RESULTS:Montelukast (6 mg/kg, once per day for 20 d) significantly suppressed the increased eosinophils in BAL fluid and lung tissue, and increased IL-5 level in BAL fluid in OVA challenged mice. OVA challenge increased CysLT1 but decreased CysLT2 receptor mRNA expression. Montelukast inhibited the increased CysLT1 but not the reduced CysLT2 expression after OVA challenge. CONCLUSION: CysLT receptors are modulated immunologically, and montelukast inhibits up-regulation of CysLT1 receptor and airway eosinophilic inflammation in asthmatic mice.

  20. Interleukin-23 and Th17 Cells in the Control of Gut Inflammation

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    Ivan Monteleone

    2009-01-01

    Full Text Available Crohn's Disease and Ulcerative Colitis, the major forms of inflammatory bowel diseases (IBDs in humans, have been traditionally associated with exaggerated and poorly controlled T helper (Th type 1 or Th2 cell response, respectively. More recent studies have, however, shown that IBDs are also characterized by a sustained production of cytokines made by a distinct lineage of Th cells, termed Th17 cells. The demonstration that Th17-related cytokines cause pathology in many organs, including the gut, and that expansion and maintenance of Th17 cell responses require the activity of IL-23, a cytokine made in excess in the gut of IBD patients has contributed to elucidate new pathways of intestinal tissue damage as well as to design new therapeutic strategies. In this review, we discuss the available data supporting the role of the IL-23/Th17 axis in the modulation of intestinal tissue inflammation.

  1. Cell-specific expression of TLR9 isoforms in inflammation.

    Science.gov (United States)

    McKelvey, Kelly J; Highton, John; Hessian, Paul A

    2011-02-01

    Toll-like receptors (TLRs) are key pattern recognition receptors during an immune response. With five isoforms of human TLR9 described, we hypothesised that differential expression of TLR9 isoforms in different cell types would result in variable contributions to the overall input from TLR9 during inflammation. We assessed the molecular expression of the TLR9 isoforms, TLR9-A, -C and -D. In normal peripheral blood mononuclear cells, B-lymphocytes express ∼100-fold more TLR9-A transcript than monocytes or T-lymphocytes, which predominantly express the TLR9-C transcript. Switches in isoform predominance accompany B-lymphocyte development. TLR9 protein expression in rheumatoid inflammatory lesions reflected the TLR9 isoform expression by immune cells. Herein we suggest that B-lymphocytes and plasmacytoid dendritic cells contribute the ∼3-fold higher TLR9-A transcript levels observed in inflamed synovium when compared to subcutaneous rheumatoid nodules. In contrast, macrophages and T-lymphocytes contribute the ∼4-fold higher TLR9-C transcript levels seen in nodules, compared to synovia. From protein sequence, predictions of subcellular localisation suggest TLR9-B may locate to the mitochondria, whereas TLR9-D adopts an opposing orientation in the endoplasmic reticulum. Consistent with this, structure models raise the possibility of alternative ligands for the TLR9-B and TLR9-D variants. Our results highlight differences in the expression of human TLR9 isoforms in normal and inflamed tissues, with differing contributions to inflammation.

  2. Visceral adipose inflammation in obesity is associated with critical alterations in tregulatory cell numbers.

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    Jeffrey Deiuliis

    Full Text Available BACKGROUND: The development of insulin resistance (IR in mouse models of obesity and type 2 diabetes mellitus (DM is characterized by progressive accumulation of inflammatory macrophages and subpopulations of T cells in the visceral adipose. Regulatory T cells (Tregs may play a critical role in modulating tissue inflammation via their interactions with both adaptive and innate immune mechanisms. We hypothesized that an imbalance in Tregs is a critical determinant of adipose inflammation and investigated the role of Tregs in IR/obesity through coordinated studies in mice and humans. METHODS AND FINDINGS: Foxp3-green fluorescent protein (GFP "knock-in" mice were randomized to a high-fat diet intervention for a duration of 12 weeks to induce DIO/IR. Morbidly obese humans without overt type 2 DM (n = 13 and lean controls (n = 7 were recruited prospectively for assessment of visceral adipose inflammation. DIO resulted in increased CD3(+CD4(+, and CD3(+CD8(+ cells in visceral adipose with a striking decrease in visceral adipose Tregs. Treg numbers in visceral adipose inversely correlated with CD11b(+CD11c(+ adipose tissue macrophages (ATMs. Splenic Treg numbers were increased with up-regulation of homing receptors CXCR3 and CCR7 and marker of activation CD44. In-vitro differentiation assays showed an inhibition of Treg differentiation in response to conditioned media from inflammatory macrophages. Human visceral adipose in morbid obesity was characterized by an increase in CD11c(+ ATMs and a decrease in foxp3 expression. CONCLUSIONS: Our experiments indicate that obesity in mice and humans results in adipose Treg depletion. These changes appear to occur via reduced local differentiation rather than impaired homing. Our findings implicate a role for Tregs as determinants of adipose inflammation.

  3. Snail modulates cell metabolism in MDCK cells

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    Haraguchi, Misako, E-mail: haraguci@m3.kufm.kagoshima-u.ac.jp [Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Indo, Hiroko P. [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Iwasaki, Yasumasa [Health Care Center, Kochi University, Kochi 780-8520 (Japan); Iwashita, Yoichiro [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Fukushige, Tomoko [Department of Dermatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Majima, Hideyuki J. [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Izumo, Kimiko; Horiuchi, Masahisa [Department of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Kanekura, Takuro [Department of Dermatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Furukawa, Tatsuhiko [Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Ozawa, Masayuki [Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan)

    2013-03-22

    Highlights: ► MDCK/snail cells were more sensitive to glucose deprivation than MDCK/neo cells. ► MDCK/snail cells had decreased oxidative phosphorylation, O{sub 2} consumption and ATP content. ► TCA cycle enzyme activity, but not expression, was lower in MDCK/snail cells. ► MDCK/snail cells showed reduced PDH activity and increased PDK1 expression. ► MDCK/snail cells showed reduced expression of GLS2 and ACLY. -- Abstract: Snail, a repressor of E-cadherin gene transcription, induces epithelial-to-mesenchymal transition and is involved in tumor progression. Snail also mediates resistance to cell death induced by serum depletion. By contrast, we observed that snail-expressing MDCK (MDCK/snail) cells undergo cell death at a higher rate than control (MDCK/neo) cells in low-glucose medium. Therefore, we investigated whether snail expression influences cell metabolism in MDCK cells. Although gylcolysis was not affected in MDCK/snail cells, they did exhibit reduced pyruvate dehydrogenase (PDH) activity, which controls pyruvate entry into the tricarboxylic acid (TCA) cycle. Indeed, the activity of multiple enzymes involved in the TCA cycle was decreased in MDCK/snail cells, including that of mitochondrial NADP{sup +}-dependent isocitrate dehydrogenase (IDH2), succinate dehydrogenase (SDH), and electron transport Complex II and Complex IV. Consequently, lower ATP content, lower oxygen consumption and increased survival under hypoxic conditions was also observed in MDCK/snail cells compared to MDCK/neo cells. In addition, the expression and promoter activity of pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates and inhibits the activity of PDH, was increased in MDCK/snail cells, while expression levels of glutaminase 2 (GLS2) and ATP-citrate lyase (ACLY), which are involved in glutaminolysis and fatty acid synthesis, were decreased in MDCK/snail cells. These results suggest that snail modulates cell metabolism by altering the expression and activity of

  4. B cell autophagy mediates TLR7-dependent autoimmunity and inflammation.

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    Weindel, Chi G; Richey, Lauren J; Bolland, Silvia; Mehta, Abhiruchi J; Kearney, John F; Huber, Brigitte T

    2015-01-01

    Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease, defined by loss of B cell self-tolerance that results in production of antinuclear antibodies (ANA) and chronic inflammation. While the initiating events in lupus development are not well defined, overexpression of the RNA-recognizing toll-like receptor (TLR)7 has been linked to SLE in humans and mice. We postulated that autophagy plays an essential role in TLR7 activation of B cells for the induction of SLE by delivering RNA ligands to the endosomes, where this innate immune receptor resides. To test this hypothesis, we compared SLE development in Tlr7 transgenic (Tg) mice with or without B cell-specific ablation of autophagy (Cd19-Cre Atg5(f/f)). We observed that in the absence of B cell autophagy the 2 hallmarks of SLE, ANA and inflammation, were eliminated, thus curing these mice of lupus. This was also evident in the significantly extended survival of the autophagy-deficient mice compared to Tlr7.1 Tg mice. Furthermore, glomerulonephritis was ameliorated, and the serum levels of inflammatory cytokines in the knockout (KO) mice were indistinguishable from those of control mice. These data provide direct evidence that B cells require TLR7-dependent priming through an autophagy-dependent mechanism before autoimmunity is induced, thereafter involving many cell types. Surprisingly, hyper-IgM production persisted in Tlr7.1 Tg mice in the absence of autophagy, likely involving a different activation pathway than the production of autoantibodies. Furthermore, these mice still presented with anemia, but responded with a striking increase in extramedullary hematopoiesis (EMH), possibly due to the absence of pro-inflammatory cytokines.

  5. Control of Cross Talk between Angiogenesis and Inflammation by Mesenchymal Stem Cells for the Treatment of Ocular Surface Diseases

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    Fei Li

    2016-01-01

    Full Text Available Angiogenesis is beneficial in the treatment of ischemic heart disease and peripheral artery disease. However, it facilitates inflammatory cell filtration and inflammation cascade that disrupt the immune and angiogenesis privilege of the avascular cornea, resulting in ocular surface diseases and even vision loss. Although great progress has been achieved, healing of severe ocular surface injury and immunosuppression of corneal transplantation are the most difficult and challenging step in the treatment of ocular surface disorders. Mesenchymal stem cells (MSCs, derived from various adult tissues, are able to differentiate into different cell types such as endothelial cells and fat cells. Although it is still under debate whether MSCs could give rise to functional corneal cells, recent results from different study groups showed that MSCs could improve corneal disease recovery through suppression of inflammation and modulation of immune cells. Thus, MSCs could become a promising tool for ocular surface disorders. In this review, we discussed how angiogenesis and inflammation are orchestrated in the pathogenesis of ocular surface disease. We overviewed and updated the knowledge of MSCs and then summarized the therapeutic potential of MSCs via control of angiogenesis, inflammation, and immune response in the treatment of ocular surface disease.

  6. Role of hypoxia-inducible factor 1α in modulating cobalt-induced lung inflammation

    OpenAIRE

    Saini, Yogesh; Kim, Kyung Y.; Lewandowski, Ryan; Bramble, Lori A.; Harkema, Jack R.; LaPres, John J.

    2009-01-01

    Hypoxia plays an important role in development, cellular homeostasis, and pathological conditions, such as cancer and stroke. There is also growing evidence that hypoxia is an important modulator of the inflammatory process. Hypoxia-inducible factors (HIFs) are a family of proteins that regulate the cellular response to oxygen deficit, and loss of HIFs impairs inflammatory cell function. There is little known, however, about the role of epithelial-derived HIF signaling in modulating inflammat...

  7. Langerhans Cells Suppress CD49a+ NK Cell-Mediated Skin Inflammation.

    Science.gov (United States)

    Scholz, Felix; Naik, Shruti; Sutterwala, Fayyaz S; Kaplan, Daniel H

    2015-09-01

    Recruitment of innate immune effector cells into sites of infection is a critical component of resistance to pathogen infection. Using a model of intradermal footpad injection of Candida albicans, we observed that inflammation as measured by footpad thickness and neutrophil recruitment occurred independent of adoptive immunity but was significantly reduced in MyD88(-/-) and IL-6(-/-) mice. Unexpectedly, huLangerin-DTA mice (ΔLC) that lack Langerhans cells (LC) developed increased skin inflammation and expressed higher amounts of IL-6, suggesting a suppressive role for LC. Increased inflammation also occurred in Rag1(-/-) ΔLC mice but was reversed by Ab-mediated ablation of NK cells. CXCR6(+)CD49a(+) NK cells are a liver-resident subset that can mediate inflammatory skin responses. We found that exaggerated skin inflammation was absent in ΔLC × CXCR6(-/-) mice. Moreover, the exaggerated response in ΔLC mice could be adoptively transferred with liver CD49a(+) NK cells. Finally, CD49a(+) NK cells in ΔLC but not control mice were recruited to the skin, and inhibition of their recruitment prevented the exaggerated response. Thus, in the absence of LC, CD49a(+) liver NK cells display an inappropriately proinflammatory phenotype that results in increased local skin inflammation. These data reveal a novel function for LC in the regulation of this recently described subset of skin tropic NK cells. PMID:26209621

  8. Iron, Inflammation, and Early Death in Adults With Sickle Cell Disease

    NARCIS (Netherlands)

    van Beers, Eduard J.; Yang, Yanqin; Raghavachari, Nalini; Tian, Xin; Allen, Darlene T.; Nichols, James S.; Mendelsohn, Laurel; Nekhai, Sergei; Gordeuk, Victor R.; Taylor, James G.; Kato, Gregory J.; van Beers, Ward

    2015-01-01

    RATIONALE:: Patients with sickle cell disease (SCD) have markers of chronic inflammation, but the mechanism of inflammation and its relevance to patient survival are unknown. OBJECTIVE:: To assess the relationship between iron, inflammation, and early death in SCD. METHODS AND RESULTS:: Using periph

  9. Osteopontin Modulates Inflammation, Mucin Production, and Gene Expression Signatures After Inhalation of Asbestos in a Murine Model of Fibrosis

    Science.gov (United States)

    Sabo-Attwood, Tara; Ramos-Nino, Maria E.; Eugenia-Ariza, Maria; MacPherson, Maximilian B.; Butnor, Kelly J.; Vacek, Pamela C.; McGee, Sean P.; Clark, Jessica C.; Steele, Chad; Mossman, Brooke T.

    2011-01-01

    Inflammation and lung remodeling are hallmarks of asbestos-induced fibrosis, but the molecular mechanisms that control these events are unclear. Using laser capture microdissection (LCM) of distal bronchioles in a murine asbestos inhalation model, we show that osteopontin (OPN) is up-regulated by bronchiolar epithelial cells after chrysotile asbestos exposures. In contrast to OPN wild-type mice (OPN+/+) inhaling asbestos, OPN null mice (OPN−/−) exposed to asbestos showed less eosinophilia in bronchoalveolar lavage fluids, diminished lung inflammation, and decreased mucin production. Bronchoalveolar lavage fluid concentrations of inflammatory cytokines (IL-1β, IL-4, IL-6, IL-12 subunit p40, MIP1α, MIP1β, and eotaxin) also were significantly less in asbestos-exposed OPN−/− mice. Microarrays performed on lung tissues from asbestos-exposed OPN+/+ and OPN−/− mice showed that OPN modulated the expression of a number of genes (Col1a2, Timp1, Tnc, Eln, and Col3a1) linked to fibrosis via initiation and cross talk between IL-1β and epidermal growth factor receptor-related signaling pathways. Novel targets of OPN identified include genes involved in cell signaling, immune system/defense, extracellular matrix remodeling, and cell cycle regulation. Although it is unclear whether the present findings are specific to chrysotile asbestos or would be observed after inhalation of other fibers in general, these results highlight new potential mechanisms and therapeutic targets for asbestosis and other diseases (asthma, smoking-related interstitial lung diseases) linked to OPN overexpression. PMID:21514415

  10. Oral manifestion of Langerhans cell histiocytosis mimicking inflammation

    Directory of Open Access Journals (Sweden)

    K S Divya

    2014-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a rare idiopathic disease characterized by the clonal proliferation of Langerhans cells. LCH affects five children per million population. The peak incidence is from 1 to 4 years of age. LCH involves the head and neck region quite commonly. Oral soft tissue lesions are also common. The differential diagnosis of oral LCH includes leukemia, neutropenia, prepubertal periodontitis, hypophosphatasia, fibrous dysplasia, and Papillon-Lefevre syndrome. The prognosis of LCH depends on early detection and appropriate management. Surgical management alone is used in 50% of cases with an additional 23% of the lesions being treated with both surgery and radiation therapy. A case of LCH in a 6-year-old girl involving the mid root level of developing first permanent molar with a floating developing tooth bud of permanent second molar mimicking an inflammation is reported.

  11. Mucosal mast cells are pivotal elements in inflammatory bowel disease that connect the dots: Stress, intestinal hyperpermeability and inflammation

    OpenAIRE

    Farhadi, Ashkan; Fields, Jeremy Z; Keshavarzian, Ali

    2007-01-01

    Mast cells (MC) are pivotal elements in several physiological and immunological functions of the gastro-intestinal (GI) tract. MC translate the stress signals that has been transmitted through brain gut axis into release of proinflammatory mediators that can cause stimulation of nerve endings that could affect afferent nerve terminals and change their perception, affect intestinal motility, increase intestinal hyperpermeability and, in susceptible individuals, modulate the inflammation. Thus,...

  12. Activation of PPARγ by a Natural Flavonoid Modulator, Apigenin Ameliorates Obesity-Related Inflammation Via Regulation of Macrophage Polarization

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    Xiujing Feng

    2016-07-01

    Full Text Available PPARγ has emerged as a master regulator of macrophage polarization and is the molecular target of the thiazolidinedione drugs. Here we show that apigenin binds and activates PPARγ by acting as a modulator. Activation of PPARγ by apigenin blocks p65 translocation into nuclei through inhibition of p65/PPARγ complex translocation into nuclei, thereby decreasing NF-κB activation and favoringM2 macrophage polarization. In HFD and ob/ob mice, apigenin significantly reverses M1 macrophage into M2 and reduces the infiltration of inflammatory cells in liver and adipose tissues, as well as decreases the levels of pro-inflammatory cytokines, thereby alleviating inflammation. Strikingly, apigenin reduces liver and muscular steatosis, decreases the levels of ALT, AST, TC and TG, improving glucose resistance obviously. Unlike rosiglitazone, apigenin does not cause significant weight gain, osteoporosis et al. Our findings identify apigenin as a modulator of PPARγ and a potential lead compound for treatment of metabolic disorders.

  13. Epithelial Cell-Neutrophil Interactions in the Alimentary Tract: A Complex Dialog in Mucosal Surveillance and Inflammation

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    Sean P. Colgan

    2002-01-01

    Full Text Available Inflammatory diseases of mucosal organs as diverse as the lung, kidney, and intestine, inevitably require the intimate interactions of neutrophils with columnar epithelia. The physiologic consequences of such interactions often determine endpoint organ function, and for this reason, much recent interest has developed in identifying mechanisms and novel targets for the treatment of mucosal inflammation. Elegant in vitro model systems incorporating purified human neutrophils and human epithelial cells grown in physiologic orientations have aided in discovery of new and insightful pathways to define basic inflammatory pathways. Here, we will review the recent literature regarding the interactions between columnar epithelial cells and neutrophils, with an emphasis on intestinal epithelial cells, structural aspects of neutrophil transepithelial migration, molecular determinants of neutrophil-epithelial cell interactions, as well as modulation of these pathways. These recent studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation.

  14. Therapeutic Down-Modulators of Staphylococcal Superantigen-Induced Inflammation and Toxic Shock

    Directory of Open Access Journals (Sweden)

    Teresa Krakauer

    2010-07-01

    Full Text Available Staphylococcal enterotoxin B (SEB and related superantigenic toxins are potent stimulators of the immune system and cause a variety of diseases in humans, ranging from food poisoning to toxic shock. These toxins bind directly to major histocompatibility complex (MHC class II molecules on antigen-presenting cells and specific Vb regions of T-cell receptors (TCR, resulting in hyperactivation of both monocytes/macrophages and T lymphocytes. Activated host cells produce massive amounts of proinflammatory cytokines and chemokines, activating inflammation and coagulation, causing clinical symptoms that include fever, hypotension, and shock. This review summarizes the in vitro and in vivo effects of staphylococcal superantigens, the role of pivotal mediators induced by these toxins in the pathogenic mechanisms of tissue injury, and the therapeutic agents to mitigate the toxic effects of superantigens.

  15. Naringin regulates cholesterol homeostasis and inhibits inflammation via modulating NF-κB and ERK signaling pathways in vitro.

    Science.gov (United States)

    Liang, Jing; Wang, Changyuan; Peng, Jinyong; Li, Wenshuang; Jin, Yue; Liu, Qi; Meng, Qiang; Liu, Kexin; Sun, Huijun

    2016-02-01

    The main purpose of this study was to examine if naringin contributed to the regulation of cholesterol homeostasis and inflammatory cytokine expressions in cholesterol and 25-OH-cholesterol-treated HepG2 cells and TNF-α-treated HUVECs. The gene and protein expressions related to cholesterol homeostasis and inflammation were determined by quantitative real-time reverse transcription-polymerase chain reaction and Western blotting. We obtained the following results: (1) A concentration-dependent increase of LDLR and CYP7A1 expressions was observed, through activating expressions of SREBP2 and PPARy in HepG2 cells after exposure to naringin; (2) EL gene and protein expressions in HUVECs were inhibited by naringin; (3) the expressions of inflammatory factors such as CRP, TNF-α, ICAM-1 and VCAM-1 in HepG2 cells, ICAM-1 and VCAM-1 in HUVECs restrained by naringin were confirmed; (4) NF-κB and ERK1/2 activities were quenched by naringin. In summary, naringin might not only effectively reduce cholesterol levels by stimulating cholesterol metabolism but also inhibit inflammatory response through reducing inflammatory cytokine expressions. The effects of naringin were achieved via modulating NF-κB and ERK signaling pathways. PMID:27004375

  16. Isoform-Specific Modulation of Inflammation Induced by Adenoviral Mediated Delivery of Platelet-Derived Growth Factors in the Adult Mouse Heart

    Science.gov (United States)

    Ylä-Herttuala, Seppo; Betsholtz, Christer; Andrae, Johanna

    2016-01-01

    Platelet-derived growth factors (PDGFs) are key regulators of mesenchymal cells in vertebrate development. To what extent PDGFs also exert beneficial homeostatic or reparative roles in adult organs, as opposed to adverse fibrogenic responses in pathology, are unclear. PDGF signaling plays critical roles during heart development, during which forced overexpression of PDGFs induces detrimental cardiac fibrosis; other studies have implicated PDGF signaling in post-infarct myocardial repair. Different PDGFs may exert different effects mediated through the two PDGF receptors (PDGFRα and PDGFRβ) in different cell types. Here, we assessed responses induced by five known PDGF isoforms in the adult mouse heart in the context of adenovirus vector-mediated inflammation. Our results show that different PDGFs have different, in some cases even opposing, effects. Strikingly, whereas the major PDGFRα agonists (PDGF-A and -C) decreased the amount of scar tissue and increased the numbers of PDGFRα-positive fibroblasts, PDGFRβ agonists either induced large scars with extensive inflammation (PDGF-B) or dampened the adenovirus-induced inflammation and produced a small and dense scar (PDGF-D). These results provide evidence for PDGF isoform-specific inflammation-modulating functions that may have therapeutic implications. They also illustrate a surprising complexity in the PDGF-mediated pathophysiological responses. PMID:27513343

  17. PV Cell and Module Calibrations at NREL

    Energy Technology Data Exchange (ETDEWEB)

    Emery, Keith

    2012-10-22

    NREL has equipment to measure any conceivable cell or module technology. The lack of standards for low concentration modules complicates matters. Spectrally adjustable simulators are critical for more than three junctions. NREL's 10-channel fiber optic simulator has shown that the light can be set for each junction within 1% of what it would be under the reference spectrum for up to a five-junction cell. Uncertainty in module simulators dominated by spatial nonuniformity for calibration labs. Manufacturers can mitigate this error by using matched reference modules instead of cells.

  18. Emerging roles of myeloid derived suppressor cells in hepatic inflammation and fibrosis

    Institute of Scientific and Technical Information of China (English)

    Linda; Hammerich; Frank; Tacke

    2015-01-01

    Myeloid derived suppressor cells(MDSC) are a heterogeneous population of immune cells that are potent suppressors of immune responses. MDSC emerge in various compartments in the body, such as blood, bonemarrow or spleen, especially in conditions of cancer, infections or inflammation. MDSC usually express CD11 b, CD33, and low levels of human leukocyte antigen-DR in humans or CD11 b and Gr1(Ly6C/G) in mice, and they can be further divided into granulocytic or monocytic MDSC. The liver is an important organ for MDSC induction and accumulation in hepatic as well as extrahepatic diseases. Different hepatic cells, especially hepatic stellate cells, as well as liver-derived soluble factors, including hepatocyte growth factor and acute phase proteins(SAA, KC), can promote the differentiation of MDSC from myeloid cells. Importantly, hepatic myeloid cells like neutrophils, monocytes and macrophages fulfill essential roles in acute and chronic liver diseases. Recent data from patients with liver diseases and animal models linked MDSC to the pathogenesis of hepatic inflammation, fibrosis and hepatocellular carcinoma(HCC). In settings of acute hepatitis, MDSC can limit immunogenic T cell responses and subsequent tissue injury. In patients with chronic hepatitis C, MDSC increase and may favor viral persistence. Animal models of chronic liver injury, however, have not yet conclusively clarified the involvement of MDSC for hepatic fibrosis. In human HCC and mouse models of liver cancer, MDSC are induced in the tumor environment and suppress anti-tumoral immune responses. Thus, the liver is a primary site of MDSC in vivo, and modulating MDSC functionality might represent a promising novel therapeutic target for liver diseases.

  19. Emerging roles of myeloid derived suppressor cells in hepatic inflammation and fibrosis.

    Science.gov (United States)

    Hammerich, Linda; Tacke, Frank

    2015-08-15

    Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immune cells that are potent suppressors of immune responses. MDSC emerge in various compartments in the body, such as blood, bone marrow or spleen, especially in conditions of cancer, infections or inflammation. MDSC usually express CD11b, CD33, and low levels of human leukocyte antigen-DR in humans or CD11b and Gr1 (Ly6C/G) in mice, and they can be further divided into granulocytic or monocytic MDSC. The liver is an important organ for MDSC induction and accumulation in hepatic as well as extrahepatic diseases. Different hepatic cells, especially hepatic stellate cells, as well as liver-derived soluble factors, including hepatocyte growth factor and acute phase proteins (SAA, KC), can promote the differentiation of MDSC from myeloid cells. Importantly, hepatic myeloid cells like neutrophils, monocytes and macrophages fulfill essential roles in acute and chronic liver diseases. Recent data from patients with liver diseases and animal models linked MDSC to the pathogenesis of hepatic inflammation, fibrosis and hepatocellular carcinoma (HCC). In settings of acute hepatitis, MDSC can limit immunogenic T cell responses and subsequent tissue injury. In patients with chronic hepatitis C, MDSC increase and may favor viral persistence. Animal models of chronic liver injury, however, have not yet conclusively clarified the involvement of MDSC for hepatic fibrosis. In human HCC and mouse models of liver cancer, MDSC are induced in the tumor environment and suppress anti-tumoral immune responses. Thus, the liver is a primary site of MDSC in vivo, and modulating MDSC functionality might represent a promising novel therapeutic target for liver diseases. PMID:26301117

  20. Obstructive Sleep Apnoea Modulates Airway Inflammation and Remodelling in Severe Asthma.

    Directory of Open Access Journals (Sweden)

    Camille Taillé

    Full Text Available Obstructive sleep apnoea (OSA is frequently observed in severe asthma but the causal link between the 2 diseases remains hypothetical. The role of OSA-related systemic and airway neutrophilic inflammation in asthma bronchial inflammation or remodelling has been rarely investigated. The aim of this study was to compare hallmarks of inflammation in induced sputum and features of airway remodelling in bronchial biopsies from adult patients with severe asthma with and without OSA.An overnight polygraphy was performed in 55 patients referred for difficult-to-treat asthma, who complained of nocturnal respiratory symptoms, poor sleep quality or fatigue. We compared sputum analysis, reticular basement membrane (RBM thickness, smooth muscle area, vascular density and inflammatory cell infiltration in bronchial biopsies.In total, 27/55 patients (49% had OSA diagnosed by overnight polygraphy. Despite a moderate increase in apnoea-hypopnoea index (AHI; 14.2 ± 1.6 event/h [5-35], the proportion of sputum neutrophils was higher and that of macrophages lower in OSA than non-OSA patients, with higher levels of interleukin 8 and matrix metalloproteinase 9. The RBM was significantly thinner in OSA than non-OSA patients (5.8 ± 0.4 vs. 7.8 ± 0.4 μm, p<0.05. RBM thickness and OSA severity assessed by the AHI were negatively correlated (rho = -0.65, p<0.05. OSA and non-OSA patients did not differ in age, sex, BMI, lung function, asthma control findings or treatment.Mild OSA in patients with severe asthma is associated with increased proportion of neutrophils in sputum and changes in airway remodelling.

  1. Inflammation-induced radioresistance is mediated by ROS-dependent inactivation of protein phosphatase 1 in non-small cell lung cancer cells.

    Science.gov (United States)

    Kim, Wanyeon; Youn, HyeSook; Kang, ChulHee; Youn, BuHyun

    2015-09-01

    Inflammation plays a pivotal role in modulating the radiation responsiveness of tumors. We determined that an inflammation response prior to irradiation contributes to radiotherapy resistance in non-small cell lung cancer (NSCLC) cells. In the clonogenic survival assay, activation of the inflammation response by lipopolysaccharide (LPS) decreased the degree of radiosensitivity in NCI-H460 cells (relatively radiosensitive cells), but had no effect in A549 cells (relatively radioresistant cells). LPS-induced radioresistance of NCI-H460 cells was also confirmed with a xenograft mouse model. The radioresistant effect observed in NCI-H460 cells was correlated with inhibition of apoptotic cell death due to reduced Caspase 3/7 activity. Moreover, we found that the levels of reactive oxygen species (ROS) were synergistically elevated in NCI-H460 cells by treatment with LPS and radiation. Increased ROS generation negatively affected the activity of protein phosphatase 1 (PP1). Decreased PP1 activity did not lead to Bad dephosphorylation, consequently resulting in the inhibition of irradiation-induced mitochondrial membrane potential loss and apoptosis. We confirmed that pre-treatment with a PP1 activator and LPS sensitized NCI-H460 cells to radiation. Taken together, our findings provided evidence that PP1 activity is critical for radiosensitization in NSCLC cells and PP1 activators can serve as promising radiosensitizers to improve therapeutic efficacy. PMID:26033480

  2. Hypercholesterolemia Tunes Hematopoietic Stem/Progenitor Cells for Inflammation and Atherosclerosis

    OpenAIRE

    Xiaojuan Ma; Yingmei Feng

    2016-01-01

    As the pathological basis of cardiovascular disease (CVD), atherosclerosis is featured as a chronic inflammation. Hypercholesterolemia is an independent risk factor for CVD. Accumulated studies have shown that hypercholesterolemia is associated with myeloid cell expansion, which stimulates innate and adaptive immune responses, strengthens inflammation, and accelerates atherosclerosis progression. Hematopoietic stem/progenitor cells (HSPC) in bone marrow (BM) expresses a panel of lipoprotein r...

  3. A Standardized Chemically Modified Curcuma longa Extract Modulates IRAK-MAPK Signaling in Inflammation and Potentiates Cytotoxicity.

    Science.gov (United States)

    Rana, Minakshi; Maurya, Preeti; Reddy, Sukka S; Singh, Vishal; Ahmad, Hafsa; Dwivedi, Anil K; Dikshit, Madhu; Barthwal, Manoj K

    2016-01-01

    The TLR/IL-1R pathway is a critical signaling module that is misregulated in pathologies like inflammation and cancer. Extracts from turmeric (Curcuma longa L.) enriched in curcumin and carbonyls like turmerones have been shown to exert potent anti-inflammatory effects. The present study evaluated the anti-inflammatory activity, cytotoxic effect and the underlying mechanism of a novel chemically modified, non-carbonyl compound enriched Curcuma longa L. (C. longa) extract (CMCE). CMCE (1 or 10 μg/mL; 14 h) significantly decreased LPS (50-100 ng/mL) induced TNF-α and IL-1β production in THP-1 cells, human, and mouse whole blood as measured by ELISA. LPS-induced IRAK1, MAPK activation, TLR4 expression, TLR4-MyD88 interaction, and IκBα degradation were significantly reduced in CMCE pre-treated THP-1 cells as assessed by Western blotting. CMCE (30, 100, and 300 mg/kg; 10 days p.o.) pre-treated and LPS (10 mg/kg) challenged Swiss mice exhibited attenuated plasma TNF-α, IL-1β, nitrite, aortic iNOS expression, and vascular dysfunction. In a PI permeability assay, cell lines derived from acute myeloid leukemia were most sensitive to the cytotoxic effects of CMCE. Analysis of Sub-G1 phase, Annexin V-PI positivity, loss of mitochondrial membrane potential, increased caspase-3, and PARP-1 activation confirmed CMCE induced apoptosis in HL-60 cells. IRAK inhibition also sensitized HL-60 cells to CMCE induced cytotoxicity. The present study defines the mechanism underlying the action of CMCE and suggests a therapeutic potential for its use in sepsis and leukemia.

  4. A Standardized Chemically Modified Curcuma longa Extract Modulates IRAK-MAPK Signaling in Inflammation and Potentiates Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Minakshi Rana

    2016-07-01

    Full Text Available The TLR/IL-1R pathway is a critical signaling module that is misregulated in pathologies like inflammation and cancer. Extracts from turmeric (Curcuma longa L. enriched in curcumin and carbonyls like turmerones have been shown to exert potent anti-inflammatory effects. The present study evaluated the anti-inflammatory activity, cytotoxic effect and the underlying mechanism of a novel chemically modified, non-carbonyl compound enriched Curcuma longa L. (C. longa extract (CMCE. CMCE (1 or 10 µg/mL; 14 h significantly decreased LPS (50-100 ng/mL induced TNF-α and IL-1β production in THP-1 cells, human, and mouse whole blood as measured by ELISA. LPS-induced IRAK1, MAPK activation, TLR4 expression, TLR4-MyD88 interaction and IκBα degradation were significantly reduced in CMCE pre-treated THP-1 cells as assessed by Western blotting. CMCE (30, 100 and 300 mg/kg; 10 days p.o. pre-treated and LPS (10 mg/kg challenged Swiss mice exhibited attenuated plasma TNF-α, IL-1β, nitrite, aortic iNOS expression and vascular dysfunction. In a PI permeability assay, cell lines derived from acute myeloid leukemia were most sensitive to the cytotoxic effects of CMCE. Analysis of Sub-G1 phase, Annexin V-PI positivity, loss of mitochondrial membrane potential, increased caspase-3 and PARP-1 activation confirmed CMCE induced apoptosis in HL-60 cells. IRAK inhibition also sensitized HL-60 cells to CMCE induced cytotoxicity. The present study defines the mechanism underlying the action of CMCE and suggests a therapeutic potential for its use in sepsis and leukemia.

  5. A Standardized Chemically Modified Curcuma longa Extract Modulates IRAK-MAPK Signaling in Inflammation and Potentiates Cytotoxicity.

    Science.gov (United States)

    Rana, Minakshi; Maurya, Preeti; Reddy, Sukka S; Singh, Vishal; Ahmad, Hafsa; Dwivedi, Anil K; Dikshit, Madhu; Barthwal, Manoj K

    2016-01-01

    The TLR/IL-1R pathway is a critical signaling module that is misregulated in pathologies like inflammation and cancer. Extracts from turmeric (Curcuma longa L.) enriched in curcumin and carbonyls like turmerones have been shown to exert potent anti-inflammatory effects. The present study evaluated the anti-inflammatory activity, cytotoxic effect and the underlying mechanism of a novel chemically modified, non-carbonyl compound enriched Curcuma longa L. (C. longa) extract (CMCE). CMCE (1 or 10 μg/mL; 14 h) significantly decreased LPS (50-100 ng/mL) induced TNF-α and IL-1β production in THP-1 cells, human, and mouse whole blood as measured by ELISA. LPS-induced IRAK1, MAPK activation, TLR4 expression, TLR4-MyD88 interaction, and IκBα degradation were significantly reduced in CMCE pre-treated THP-1 cells as assessed by Western blotting. CMCE (30, 100, and 300 mg/kg; 10 days p.o.) pre-treated and LPS (10 mg/kg) challenged Swiss mice exhibited attenuated plasma TNF-α, IL-1β, nitrite, aortic iNOS expression, and vascular dysfunction. In a PI permeability assay, cell lines derived from acute myeloid leukemia were most sensitive to the cytotoxic effects of CMCE. Analysis of Sub-G1 phase, Annexin V-PI positivity, loss of mitochondrial membrane potential, increased caspase-3, and PARP-1 activation confirmed CMCE induced apoptosis in HL-60 cells. IRAK inhibition also sensitized HL-60 cells to CMCE induced cytotoxicity. The present study defines the mechanism underlying the action of CMCE and suggests a therapeutic potential for its use in sepsis and leukemia. PMID:27504095

  6. Blockage of caspase-1 activation ameliorates bone marrow inflammation in mice after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Qiao, Jianlin; Wu, Jinyan; Li, Yuanyuan; Xia, Yuan; Chu, Peipei; Qi, Kunming; Yan, Zhiling; Yao, Haina; Liu, Yun; Xu, Kailin; Zeng, Lingyu

    2016-01-01

    Conditioning regimens before hematopoietic stem cell transplantation (HSCT), cause damage to bone marrow and inflammation. Whether inflammasomes are involved in bone marrow inflammation remains unclear. The study aims to evaluate the role of inflammasomes in bone marrow inflammation after HSCT. On days 7, 14, 21 and 28 after HSCT, mice were sacrificed for analysis of bone marrow inflammation, pro-inflammatory cytokines secretion, inflammasomes expression and caspase-1 activation. Bone marrow inflammation with neutrophils and macrophages infiltration was observed after HSCT. Secretion of IL-1β, IL-18, TNF-α and IL-6 were elevated, with increased caspase-1 activation and inflammasomes expression. Caspase-1 inhibitor administration after HSCT significantly reduced infiltration of neutrophils and macrophages into bone marrow and increased the numbers of megakaryocytes and platelets. In conclusion, inflammasomes activation is involved in bone marrow inflammation after HSCT and caspase-1 inhibition attenuates bone marrow inflammation and promoted hematopoietic reconstitution, suggesting targeting caspase-1 might be beneficial for improving HSCT outcomes.

  7. New Insights into the Role of Macrophages in Adipose Tissue Inflammation and Fatty Liver Disease: Modulation by Endogenous Omega-3 Fatty Acid-derived Lipid Mediators

    Directory of Open Access Journals (Sweden)

    Joan eClària

    2011-10-01

    Full Text Available Obesity is causally linked to a chronic state of low-grade inflammation in adipose tissue. Prolonged, unremitting inflammation in this tissue has a direct impact on insulin-sensitive tissues (i.e. liver and its timely resolution is a critical step toward reducing the prevalence of related co-morbidities such as insulin resistance and non-alcoholic fatty liver disease. This article describes the current state-of-the-art knowledge and novel insights into the role of macrophages in adipose tissue inflammation, with special emphasis on the progressive changes in macrophage polarization observed over the course of obesity. In addition, this article extends the discussion to the contribution of Kupffer cells, the liver resident macrophages, to metabolic liver disease. Special attention is given to the modulation of macrophage responses by omega-3-PUFAs, and more importantly by resolvins, which are potent anti-inflammatory and pro-resolving autacoids generated from docosahexaenoic and eicosapentaenoic acids. In fact, resolvins have been shown to work as endogenous stop signals in inflamed adipose tissue and to return this tissue to homeostasis by inducing a phenotypic switch in macrophage polarization toward a pro-resolving phenotype. Collectively, this article offers new views on the role of macrophages in metabolic disease and their modulation by endogenously-generated omega-3-PUFA-derived lipid mediators.

  8. Eosinophils Modulate CD4+ T Cell Responses via High Mobility Group Box-1 in the Pathogenesis of Asthma

    OpenAIRE

    Shim, Eun-Jin; Chun, Eunyoung; Lee, Hyun-Seung; Bang, Bo-Ram; Cho, Sang-Heon; Min, Kyung-Up; Park, Heung-Woo

    2014-01-01

    Eosinophils have been reported to modulate T cell responses. Previously, we reported that high-mobility group box 1 protein (HMGB1) played a key role in the pathogenesis of asthma. This study was conducted to test our hypothesis that eosinophils could modulate T cell responses via HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation. We performed in vitro experiments using eosinophils, dendritic cells (DCs), and CD4+ T cells obtained from a murine model of ast...

  9. An extract of Crataegus pinnatifida fruit attenuates airway inflammation by modulation of matrix metalloproteinase-9 in ovalbumin induced asthma.

    Directory of Open Access Journals (Sweden)

    In Sik Shin

    Full Text Available BACKGROUND: Crataegus pinnatifida (Chinese hawthorn has long been used as a herbal medicine in Asia and Europe. It has been used for the treatment of various cardiovascular diseases such as myocardial weakness, tachycardia, hypertension and arteriosclerosis. In this study, we investigated the anti-inflammatory effects of Crataegus pinnatifida ethanolic extracts (CPEE on Th2-type cytokines, eosinophil infiltration, expression of matrix metalloproteinase (MMP-9, and other factors, using an ovalbumin (OVA-induced murine asthma model. METHODS/PRINCIPAL FINDING: Airways of OVA-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. CPEE was applied 1 h prior to OVA challenge. Mice were administered CPEE orally at doses of 100 and 200 mg/kg once daily on days 18-23. Bronchoalveolar lavage fluid (BALF was collected 48 h after the final OVA challenge. Levels of interleukin (IL-4 and IL-5 in BALF were measured using enzyme-linked immunosorbent (ELISA assays. Lung tissue sections 4 µm in thickness were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration and mucus production with PAS staining, in conjunction with ELISA, and Western blot analyses for the expression of MMP-9, intercellular adhesion molecule (ICAM-1 and vascular cell adhesion molecule (VCAM-1 protein expression. CPEE significantly decreased the Th2 cytokines including IL-4 and IL-5 levels, reduced the number of inflammatory cells in BALF and airway hyperresponsiveness, suppressed the infiltration of eosinophil-rich inflammatory cells and mucus hypersecretion and reduced the expression of ICAM-1, VCAM-1 and MMP-9 and the activity of MMP-9 in lung tissue of OVA-challenged mice. CONCLUSIONS: These results showed that CPEE can protect against allergic airway inflammation and can act as an MMP-9 modulator to induce a reduction in ICAM-1 and VCAM-1 expression. In conclusion, we strongly suggest the feasibility

  10. Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell death through redox-dependent signaling.

    Directory of Open Access Journals (Sweden)

    Dong-Min Shin

    Full Text Available The "enhanced intracellular survival" (eis gene of Mycobacterium tuberculosis (Mtb is involved in the intracellular survival of M. smegmatis. However, its exact effects on host cell function remain elusive. We herein report that Mtb Eis plays essential roles in modulating macrophage autophagy, inflammatory responses, and cell death via a reactive oxygen species (ROS-dependent pathway. Macrophages infected with an Mtb eis-deletion mutant H37Rv (Mtb-Δeis displayed markedly increased accumulation of massive autophagic vacuoles and formation of autophagosomes in vitro and in vivo. Infection of macrophages with Mtb-Δeis increased the production of tumor necrosis factor-α and interleukin-6 over the levels produced by infection with wild-type or complemented strains. Elevated ROS generation in macrophages infected with Mtb-Δeis (for which NADPH oxidase and mitochondria were largely responsible rendered the cells highly sensitive to autophagy activation and cytokine production. Despite considerable activation of autophagy and proinflammatory responses, macrophages infected with Mtb-Δeis underwent caspase-independent cell death. This cell death was significantly inhibited by blockade of autophagy and c-Jun N-terminal kinase-ROS signaling, suggesting that excessive autophagy and oxidative stress are detrimental to cell survival. Finally, artificial over-expression of Eis or pretreatment with recombinant Eis abrogated production of both ROS and proinflammatory cytokines, which depends on the N-acetyltransferase domain of the Eis protein. Collectively, these data indicate that Mtb Eis suppresses host innate immune defenses by modulating autophagy, inflammation, and cell death in a redox-dependent manner.

  11. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice.

    Science.gov (United States)

    Duerr, Georg D; Dewald, Daniela; Schmitz, Eva J; Verfuerth, Luise; Keppel, Katharina; Peigney, Christine; Ghanem, Alexander; Welz, Armin; Dewald, Oliver

    2016-01-01

    Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT(-/-))-mice (n = 8-10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT(-/-)-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2(-/-)-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT(-/-)-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2(-/-)-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling. PMID:27403038

  12. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice

    Directory of Open Access Journals (Sweden)

    Georg D. Duerr

    2016-01-01

    Full Text Available Aims. Repetitive brief ischemia and reperfusion (I/R is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT- and MT1/2 knockout (MT-/--mice (n = 8–10/group. Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT-/--hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2-/--hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT-/--hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2-/--hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling.

  13. Modulation of Visceral Nociception, Inflammation and Gastric Mucosal Injury by Cinnarizine

    Directory of Open Access Journals (Sweden)

    Omar M.E. Abdel-Salam

    2007-01-01

    Full Text Available The effect of cinnarizine, a drug used for the treatment of vertigo was assessed in animal models of visceral nociception, inflammation and gastric mucosal injury. Cinnarizine (1.25–20 mg/kg, s.c. caused dose-dependent inhibition of the abdominal constrictions evoked by i.p. injection of acetic acid by 38.7–99.4%. This effect of cinnarizine (2.5 mg/kg was unaffected by co-administration of the centrally acting dopamine D2 receptor antagonists, sulpiride, haloperidol or metoclopramide, the peripherally acting D2 receptor antagonist domperidone, but increased by the D2 receptor agonist bromocryptine and by the non-selective dopamine receptor antagonist chlorpromazine. The antinociception caused by cinnarizine was naloxone insenstive, but enhanced by propranolol, atropine and by yohimbine. The antinociceptive effect of cinnarizine was prevented by co-treatment with the adenosine receptor blocker theophylline or by the ATP-sensitive potassium channel (KATP blocker glibenclamide. Cinnarizine at 2.5 mg/kg reversed the baclofen-induced antinociception. Cinnarizine at 2.5 mg/kg reduced immobility time in the Porsolt’s forced-swimming test by 24%. Cinnarizine inhibited the paw oedema response to carrageenan and reduced gastric mucosal lesions caused by indomethacin in rats. It is suggested that cinnarizine exerts anti-infl ammatory, antinociceptive and gastric protective properties. The mechanism by which cinnarizine modulates pain transmission is likely to involve adenosine receptors and KATP channels.

  14. Modulation of visceral nociception, inflammation and gastric mucosal injury by cinnarizine.

    Science.gov (United States)

    Abdel-Salam, Omar M E

    2007-01-01

    The effect of cinnarizine, a drug used for the treatment of vertigo was assessed in animal models of visceral nociception, inflammation and gastric mucosal injury. Cinnarizine (1.25-20 mg/kg, s.c.) caused dose-dependent inhibition of the abdominal constrictions evoked by i.p. injection of acetic acid by 38.7-99.4%. This effect of cinnarizine (2.5 mg/kg) was unaffected by co-administration of the centrally acting dopamine D2 receptor antagonists, sulpiride, haloperidol or metoclopramide, the peripherally acting D2 receptor antagonist domperidone, but increased by the D2 receptor agonist bromocryptine and by the non-selective dopamine receptor antagonist chlorpromazine. The antinociception caused by cinnarizine was naloxone insenstive, but enhanced by propranolol, atropine and by yohimbine. The antinociceptive effect of cinnarizine was prevented by co-treatment with the adenosine receptor blocker theophylline or by the ATP-sensitive potassium channel (K(ATP)) blocker glibenclamide. Cinnarizine at 2.5 mg/kg reversed the baclofen-induced antinociception. Cinnarizine at 2.5 mg/kg reduced immobility time in the Porsolt's forced-swimming test by 24%. Cinnarizine inhibited the paw oedema response to carrageenan and reduced gastric mucosal lesions caused by indomethacin in rats. It is suggested that cinnarizine exerts anti-inflammatory, antinociceptive and gastric protective properties. The mechanism by which cinnarizine modulates pain transmission is likely to involve adenosine receptors and K(ATP) channels. PMID:21901060

  15. Mucosal mast cells are pivotal elements in inflammatory bowel disease that connect the dots: Stress, intestinal hyperpermeability and inflammation

    Institute of Scientific and Technical Information of China (English)

    Ashkan Farhadi; Jeremy Z Fields; Ali Keshavarzian

    2007-01-01

    Mast cells (MC) are pivotal elements in several physiological and immunological functions of the gastrointestinal (GI) tract. MC translate the stress signals that has been transmitted through brain gut axis into release of proinflammatory mediators that can cause stimulation of nerve endings that could affect afferent nerve terminals and change their perception, affect intestinal motility, increase intestinal hyperpermeability and, in susceptible individuals, modulate the inflammation. Thus, it is not surprising that MC are an important element in the pathogenesis of inflammatory bowel disease and non inflammatory GI disorders such as IBS and mast cell enterocolitis.

  16. Macrophages and dendritic cells emerge in the liver during intestinal inflammation and predispose the liver to inflammation.

    Directory of Open Access Journals (Sweden)

    Yohei Mikami

    Full Text Available The liver is a physiological site of immune tolerance, the breakdown of which induces immunity. Liver antigen-presenting cells may be involved in both immune tolerance and activation. Although inflammatory diseases of the liver are frequently associated with inflammatory bowel diseases, the underlying immunological mechanisms remain to be elucidated. Here we report two murine models of inflammatory bowel disease: RAG-2(-/- mice adoptively transferred with CD4(+CD45RB(high T cells; and IL-10(-/- mice, accompanied by the infiltration of mononuclear cells in the liver. Notably, CD11b(-CD11c(lowPDCA-1(+ plasmacytoid dendritic cells (DCs abundantly residing in the liver of normal wild-type mice disappeared in colitic CD4(+CD45RB(high T cell-transferred RAG-2(-/- mice and IL-10(-/- mice in parallel with the emergence of macrophages (Mφs and conventional DCs (cDCs. Furthermore, liver Mφ/cDCs emerging during intestinal inflammation not only promote the proliferation of naïve CD4(+ T cells, but also instruct them to differentiate into IFN-γ-producing Th1 cells in vitro. The emergence of pathological Mφ/cDCs in the liver also occurred in a model of acute dextran sulfate sodium (DSS-induced colitis under specific pathogen-free conditions, but was canceled in germ-free conditions. Last, the Mφ/cDCs that emerged in acute DSS colitis significantly exacerbated Fas-mediated hepatitis. Collectively, intestinal inflammation skews the composition of antigen-presenting cells in the liver through signaling from commensal bacteria and predisposes the liver to inflammation.

  17. Assembly jig assures reliable solar cell modules

    Science.gov (United States)

    Ofarrell, H. O.

    1966-01-01

    Assembly jig holds the components for a solar cell module in place as the assembly is soldered and bonded by the even heat of an oven. The jig is designed to the configuration of the planned module. It eliminates uneven thermal conditions caused by hand soldering methods.

  18. Cell shunt resistance and photovoltaic module performance

    Energy Technology Data Exchange (ETDEWEB)

    McMahon, T.J.; Basso, T.S.; Rummel, S.R. [National Renewable Energy Lab., Golden, CO (United States)

    1996-05-01

    Shunt resistance of cells in photovoltaic modules can affect module power output and could indicate flawed manufacturing processes and reliability problems. The authors describe a two-terminal diagnostic method to directly measure the shunt resistance of individual cells in a series-connected module non-intrusively, without deencapsulation. Peak power efficiency vs. light intensity was measured on a 12-cell, series-connected, single crystalline module having relatively high cell shunt resistances. The module was remeasured with 0.5-, 1-, and 2-ohm resistors attached across each cell to simulate shunt resistances of several emerging technologies. Peak power efficiencies decreased dramatically at lower light levels. Using the PSpice circuit simulator, the authors verified that cell shunt and series resistances can indeed be responsible for the observed peak power efficiency vs. intensity behavior. The authors discuss the effect of basic cell diode parameters, i.e., shunt resistance, series resistance, and recombination losses, on PV module performance as a function of light intensity.

  19. PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation.

    Science.gov (United States)

    Dammann, Kyle; Khare, Vineeta; Lang, Michaela; Claudel, Thierry; Harpain, Felix; Granofszky, Nicolas; Evstatiev, Rayko; Williams, Jonathan M; Pritchard, D Mark; Watson, Alastair; Gasche, Christoph

    2015-10-01

    P21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases with both kinase and scaffolding activity. Here, we investigated the effects of inflammation on PAK1 signaling and its role in colitis-driven carcinogenesis. PAK1 and p-PAK1 (Thr423) were assessed by immunohistochemistry, immunofluorescence, and Western blot. C57BL6/J wildtype mice were treated with a single intraperitoneal TNFα injection. Small intestinal organoids from these mice and from PAK1-KO mice were cultured with TNFα. NF-κB and PPARγ were analyzed upon PAK1 overexpression and silencing for transcriptional/translational regulation. PAK1 expression and activation was increased on the luminal intestinal epithelial surface in inflammatory bowel disease and colitis-associated cancer. PAK1 was phosphorylated upon treatment with IFNγ, IL-1β, and TNFα. In vivo, mice administered with TNFα showed increased p-PAK1 in intestinal villi, which was associated with nuclear p65 and NF-κB activation. p65 nuclear translocation downstream of TNFα was strongly inhibited in PAK1-KO small intestinal organoids. PAK1 overexpression induced a PAK1-p65 interaction as visualized by co-immunoprecipitation, nuclear translocation, and increased NF-κB transactivation, all of which were impeded by kinase-dead PAK1. Moreover, PAK1 overexpression downregulated PPARγ and mesalamine recovered PPARγ through PAK1 inhibition. On the other hand PAK1 silencing inhibited NF-κB, which was recovered using BADGE, a PPARγ antagonist. Altogether these data demonstrate that PAK1 overexpression and activation in inflammation and colitis-associated cancer promote NF-κB activity via suppression of PPARγ in intestinal epithelial cells.

  20. Characterization of bladder sensory neurons in the context of myelination, receptors for pain modulators, and acute responses to bladder inflammation

    OpenAIRE

    Shelley L Forrest; Osborne, Peregrine B.; Keast, Janet R.

    2013-01-01

    Bladder sensation is mediated by lumbosacral dorsal root ganglion neurons and is essential for normal voiding and nociception. Numerous electrophysiological, structural and molecular changes occur in these neurons following inflammation. Defining which neurons undergo these changes is critical for understanding the mechanism underlying bladder pain and dysfunction. Our first aim was to define the chemical classes of bladder sensory neurons that express receptors for the endogenous modulators ...

  1. Joint inflammations and exacerbations in mice by cloned helper T cells

    NARCIS (Netherlands)

    I. Klasen (Ina)

    1988-01-01

    textabstractBriefly, the aim of the study described in this thesis was to investigate whether the joint inflammations that occur in AlA can also be induced by cloned helper T cells and the antigen they recognize, and whether these joint inflammations can also show flare-up phenomena after repeated a

  2. T-cell activation promotes tumorigenesis in inflammation-associated cancer

    Directory of Open Access Journals (Sweden)

    Lairmore Michael

    2009-12-01

    Full Text Available Abstract Chronic inflammation has long been associated with a wide range of malignancies, is now widely accepted as a risk factor for development of cancer, and has been implicated as a promoter of a variety of cancers including hematopoietic malignancies. We have described a mouse model uniquely suited to examine the link between inflammation and lymphoma in which the Tax oncogene, expressed in activated T and NK cells, perpetuates chronic inflammation that begins as microscopic intraepithelial lesions and develops into inflammatory nodules, subcutaneous tumors, and large granular lymphocytic leukemia. The use of bioluminescent imaging in these mice has expanded our ability to interrogate aspects of inflammation and tumorigenesis non-invasively. Here we demonstrate that bioluminescence induction in these mice correlated with inflammation resulting from wounding, T cell activation, and exposure to chemical agents. In experiments in which long-term effects of inflammation on disease outcome were monitored, the development of lymphoma was promoted by an inflammatory stimulus. Finally we demonstrated that activation of T-cells in T-cell receptor (TCR transgenic TAX-LUC animals dramatically exacerbated the development of subcutaneous TCR- CD16+ LGL tumors. The role of activated T-cells and acquired immunity in inflammation-associated cancers is broadly applicable to hematopoietic malignancies, and we propose these mice will be of use in dissecting mechanisms by which activated T-cells promote lymphomagenesis in vivo.

  3. Nanostructures to modulate vascular inflammation: Multifunctional nanoparticles for quantifiable siRNA delivery and molecular imaging

    Science.gov (United States)

    Kaneda, Megan Marie

    Early steps in the progression of inflammatory diseases such as atherosclerosis involve the recruitment of leukocytes to the vascular endothelium through the expression or up-regulation of adhesion molecules. These adhesion molecules are critical mediators of leukocyte attachment and subsequent extravasation through transendothelial migration. One of these adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) is particularly attractive as a marker of early atherosclerotic activity due to its low expression level on normal endothelium and up-regulation prior to and during the development of early lesions. With this in mind, the purpose of this thesis was to develop nanostructures for the detection and down-regulation of adhesion molecules by the vascular endothelium. To detect early inflammation we designed a perfluorocarbon nanoparticle (PFC-NP) probe, which was used for in vivo targeting of VCAM-1. Nanoparticles were detected ex vivo by the magnetic resonance (MR) signature from the fluorine core of the particle. Nanoparticles accumulated in tissues characterized by early inflammatory processes. To down-regulate VCAM-1 expression by vascular endothelial cells, cationic PFC-NP were produced through the addition of the cationic lipid 1,2-Dioleoyl-3-Trimethylammonium-Propane. Cationic PFC-NP were able to deliver anti-VCAM-1 siRNA to endothelial cells through a non-standard lipid raft mediated endocytic pathway. VCAM-1 levels were significantly reduced in treated cells indicating that this delivery mechanism may be advantageous for delivery of cargo into the cytoplasm. Using the fluorine signature from the core of the cationic PFC-NP, we were able to quantify and localize this siRNA delivery agent both in vitro and in vivo. The ability to quantify the local concentrations of these particles could be of great benefit for estimating local drug concentrations and developing new pharmacokinetic and pharmacodynamic paradigms to describe this new class of

  4. In vitro evaluation of the cytotoxicity and modulation of mechanisms associated with inflammation induced by perfluorooctanesulfonate and perfluorooctanoic acid in human colon myofibroblasts CCD-18Co.

    Science.gov (United States)

    Giménez-Bastida, Juan Antonio; Surma, Magdalena; Zieliński, Henryk

    2015-10-01

    Perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the most notable members of an emerging class of persistent organic pollutants (POPs), poly- and perfluoroalkyl acids (PFASs). In this study, the CCD-18Co myofibroblasts were selected as a cell model to investigate the cytotoxic effects of PFOS and PFOA. The aim was to perform an in vitro evaluation of the ability of these compounds to induce cytotoxicity and modulate mechanisms associated with inflammation as measured by (i) colon fibroblasts viability, (ii) colon fibroblasts proliferation, and (iii) IL-6 production. The data provided in this study suggest that PFOS and PFOA can have cytotoxic potential and modulate processes associated with intestinal inflammation such as myofibroblasts proliferation and IL-6 production at concentrations similar to those detected in vivo. Our results also highlight the influence of culture serum concentration in cytotoxic in vitro studies, which should be considered in future toxicity studies involving PFOS and PFOA. The results contribute to a better knowledge of the effects of PFOS and PFOA in human cells, a phenomenon still not fully examined. PMID:26142696

  5. IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.

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    Catherine Q Nie

    2009-04-01

    Full Text Available Plasmodium falciparum malaria causes 660 million clinical cases with over 2 million deaths each year. Acquired host immunity limits the clinical impact of malaria infection and provides protection against parasite replication. Experimental evidence indicates that cell-mediated immune responses also result in detrimental inflammation and contribute to severe disease induction. In both humans and mice, the spleen is a crucial organ involved in blood stage malaria clearance, while organ-specific disease appears to be associated with sequestration of parasitized erythrocytes in vascular beds and subsequent recruitment of inflammatory leukocytes. Using a rodent model of cerebral malaria, we have previously found that the majority of T lymphocytes in intravascular infiltrates of cerebral malaria-affected mice express the chemokine receptor CXCR3. Here we investigated the effect of IP-10 blockade in the development of experimental cerebral malaria and the induction of splenic anti-parasite immunity. We found that specific neutralization of IP-10 over the course of infection and genetic deletion of this chemokine in knockout mice reduces cerebral intravascular inflammation and is sufficient to protect P. berghei ANKA-infected mice from fatality. Furthermore, our results demonstrate that lack of IP-10 during infection significantly reduces peripheral parasitemia. The increased resistance to infection observed in the absence of IP-10-mediated cell trafficking was associated with retention and subsequent expansion of parasite-specific T cells in spleens of infected animals, which appears to be advantageous for the control of parasite burden. Thus, our results demonstrate that modulating homing of cellular immune responses to malaria is critical for reaching a balance between protective immunity and immunopathogenesis.

  6. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice

    Science.gov (United States)

    Dewald, Daniela; Schmitz, Eva J.; Verfuerth, Luise; Keppel, Katharina; Peigney, Christine; Ghanem, Alexander; Welz, Armin; Dewald, Oliver

    2016-01-01

    Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT−/−)-mice (n = 8–10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT−/−-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2−/−-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT−/−-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2−/−-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling. PMID:27403038

  7. Peroxisome proliferator-activated receptor gamma as modulator of inflammation in pulmonary sarcoidosis

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    Pejčić Tatjana

    2013-01-01

    Full Text Available Peroxisome proliferator-activated receptor (PPAR includes the family of ligand-activated transcription factors which belong to the group of nuclear hormone receptors and are connected to retinoid, glucocorticoid and thyroid hormone receptors. There are three subtypes of PPARs: PPARα (also known as NR1C3, PPARγ (known as NR1C1 and PPARδ (known as PPARβ or NR1C2. All of them take part in the metabolism, cell proliferation and immune response. PPARγ and PPARα are identified as important immunomodulators and potentially represent an anti-inflammatory target for respiratory diseases. PPARγ deficiency in the lungs has been observed in the inflammatory diseases such as asthma, pulmonary alveolar proteinosis, fibrosis and sarcoidosis, as well as in the animal models of the lung inflammation. A small number of papers concerned with PPARγ in sarcoidosis point to the lowered activity of this factor in the alveolar macrophages and a lowered gene expression for the PPARγ, while the activity is preserved in healthy individuals. At the same time, an increased activity of the nuclear factor kappa B (NF-kB in the bronchoalveolar lavage has been recorded in patients with sarcoidosis. The reason for the decrease in the production of PPARγ in sarcoidosis remains unknown. Several possible mechanisms are mentioned: genetic defect with lowered production, down-regulation due to the increased values of IFN-γ or an increased decomposition of PPARγ. Further investigation will explain the mechanisms regarding the decreased production of PPARγ in sarcoidosis.

  8. Lung effector memory and activated CD4+ T cells display enhanced proliferation in SP-A-deficient mice during allergen-mediated inflammation

    OpenAIRE

    Pastva, Amy M.; Mukherjee, Sambuddho; Giamberardino, Charles; Hsia, Bethany; Lo, Bernice; Sempowski, Gregory D; Wright, Jo Rae

    2011-01-01

    Although many studies show that pulmonary Surfactant Protein A (SP-A) functions in innate immunity, fewer studies have addressed its role in adaptive immunity and allergic hypersensitivity. We hypothesized that SP-A modulates the phenotype and prevalence of dendritic cells (DCs) and CD4+ T cells to inhibit Th2-associated inflammatory indices associated with allergen-induced inflammation. In an ovalbumin (OVA) model of allergic hypersensitivity, SP-A deficient (SP-A−/−) mice had greater eosino...

  9. Slit2-Robo4 pathway modulates lipopolysaccharide-induced endothelial inflammation and its expression is dysregulated during endotoxemia.

    Science.gov (United States)

    Zhao, Helong; Anand, Appakkudal R; Ganju, Ramesh K

    2014-01-01

    The secretory protein Slit2 and its receptors Robo1 and Robo4 are considered to regulate mobility and permeability of endothelial cells and other cell types. However, the roles of Slit2 and its two receptors in endothelial inflammatory responses remain to be clarified. In this study, we show that, in primary HUVECs, Slit2 represses LPS-induced secretion of certain inflammatory cytokines/chemokines, cell adhesion molecule ICAM-1 upregulation, and monocyte adhesion. Slit2's anti-inflammatory effect is mediated by its dominant endothelial-specific receptor Robo4. However, the minor receptor Robo1 has proinflammatory properties and is downregulated by Slit2 via targeting of miR-218. Elucidation of molecular mechanism reveals that Slit2 represses inflammatory responses by inhibiting the Pyk2-NF-κB pathway downstream of LPS-TLR4. Further studies reveal that LPS enhances endothelial inflammation by downregulating the anti-inflammatory Slit2 and Robo4 in HUVECs in vitro, as well as in arterial endothelial cells and liver in vivo during endotoxemia. These results suggest that Slit2-Robo4 signaling is important in regulating LPS-induced endothelial inflammation, and LPS, in turn, enhances inflammation by interfering with the expression of the anti-inflammatory Slit2-Robo4 during the disease state. This implies that Slit2-Robo4 is a key regulator of endothelial inflammation, and its dysregulation during endotoxemia is a novel mechanism for LPS-induced vascular pathogenesis.

  10. Inflammation, glucose, and vascular cell damage: the role of the pentose phosphate pathway

    OpenAIRE

    Peiró, Concepción; Romacho, Tania; Azcutia, Verónica; Villalobos, Laura; Fernández, Emilio; Bolaños, Juan P.; Moncada, Salvador; Sánchez-Ferrer, Carlos F

    2016-01-01

    Background Hyperglycemia is acknowledged as a pro-inflammatory condition and a major cause of vascular damage. Nevertheless, we have previously described that high glucose only promotes inflammation in human vascular cells previously primed with pro-inflammatory stimuli, such as the cytokine interleukin (IL)1β. Here, we aimed to identify the cellular mechanisms by which high glucose exacerbates the vascular inflammation induced by IL1β. Methods Cultured human aortic smooth muscle cells (HASMC...

  11. Linking CD11b+ Dendritic Cells and Natural Killer T Cells to Plaque Inflammation in Atherosclerosis

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    Miche Rombouts

    2016-01-01

    Full Text Available Atherosclerosis remains the leading cause of death and disability in our Western society. To investigate whether the dynamics of leukocyte (subpopulations could be predictive for plaque inflammation during atherosclerosis, we analyzed innate and adaptive immune cell distributions in blood, plaques, and lymphoid tissue reservoirs in apolipoprotein E-deficient (ApoE−/− mice and in blood and plaques from patients undergoing endarterectomy. Firstly, there was predominance of the CD11b+ conventional dendritic cell (cDC subset in the plaque. Secondly, a strong inverse correlation was observed between CD11b+ cDC or natural killer T (NKT cells in blood and markers of inflammation in the plaque (including CD3, T-bet, CCR5, and CCR7. This indicates that circulating CD11b+ cDC and NKT cells show great potential to reflect the inflammatory status in the atherosclerotic plaque. Our results suggest that distinct changes in inflammatory cell dynamics may carry biomarker potential reflecting atherosclerotic lesion progression. This not only is crucial for a better understanding of the immunopathogenesis but also bares therapeutic potential, since immune cell-based therapies are emerging as a promising novel strategy in the battle against atherosclerosis and its associated comorbidities. The cDC-NKT cell interaction in atherosclerosis serves as a good candidate for future investigations.

  12. Ozone-Induced Pulmonary Injury and Inflammation are Modulated by Adrenal-Derived Stress Hormones

    Science.gov (United States)

    Ozone exposure promotes pulmonary injury and inflammation. Previously we have characterized systemic changes that occur immediately after acute ozone exposure and are mediated by neuro-hormonal stress response pathway. Both HPA axis and sympathetic tone alterations induce the rel...

  13. Insight in modulation of inflammation in response to diclofenac intervention : A human intervention study

    NARCIS (Netherlands)

    Erk, M.J. van; Wopereis, S.; Rubingh, C.; Vliet, T. van; Verheij, E.; Cnubben, N.H.; Pedersen, T.L.; Newman, J.W.; Smilde, A.K.; Greef, J.V.D.; Hendriks, H.F.; Ommen, B. van

    2010-01-01

    Background. Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately des

  14. Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation.

    Science.gov (United States)

    Monticelli, Laurel A; Buck, Michael D; Flamar, Anne-Laure; Saenz, Steven A; Tait Wojno, Elia D; Yudanin, Naomi A; Osborne, Lisa C; Hepworth, Matthew R; Tran, Sara V; Rodewald, Hans-Reimer; Shah, Hardik; Cross, Justin R; Diamond, Joshua M; Cantu, Edward; Christie, Jason D; Pearce, Erika L; Artis, David

    2016-06-01

    Group 2 innate lymphoid cells (ILC2s) regulate tissue inflammation and repair after activation by cell-extrinsic factors such as host-derived cytokines. However, the cell-intrinsic metabolic pathways that control ILC2 function are undefined. Here we demonstrate that expression of the enzyme arginase-1 (Arg1) during acute or chronic lung inflammation is a conserved trait of mouse and human ILC2s. Deletion of mouse ILC-intrinsic Arg1 abrogated type 2 lung inflammation by restraining ILC2 proliferation and dampening cytokine production. Mechanistically, inhibition of Arg1 enzymatic activity disrupted multiple components of ILC2 metabolic programming by altering arginine catabolism, impairing polyamine biosynthesis and reducing aerobic glycolysis. These data identify Arg1 as a key regulator of ILC2 bioenergetics that controls proliferative capacity and proinflammatory functions promoting type 2 inflammation. PMID:27043409

  15. Modulation of monocyte/macrophage-derived cytokine and chemokine profile by persistent Hepatitis C virus (HCV infection leads to chronic inflammation

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    Penelope Mavromara

    2012-02-01

    Full Text Available HCV infection presents a major public health problem, with more than 170 million people infected worldwide. Chronicity and persistence of infection constitute the hallmark of the disease. Although HCV is a hepatotropic virus, subsets of immune cells have been found to be permissive to infection and viral replication. Peripheral blood monocytes, attracted to the site of infection and differentiated into macrophages, and resident hepatic macrophages, known as Kupffer cells, are important mediators of innate immunity, through production of several chemokines and cytokines in addition to their phagocytic activity. HCV proteins have been shown to modulate the cytokine and chemokine production profile of monocytes/macrophages, as it is suggested by both in vitro and clinical studies. This modified expression profile appears crucial for the establishment of aberrant inflammation that leads to liver cirrhosis and hepatocellular carcinoma.

  16. Recent advances in understanding the roles of vascular endothelial cells in allergic inflammation.

    Science.gov (United States)

    Shoda, Tetsuo; Futamura, Kyoko; Orihara, Kanami; Emi-Sugie, Maiko; Saito, Hirohisa; Matsumoto, Kenji; Matsuda, Akio

    2016-01-01

    Allergic disorders commonly involve both chronic tissue inflammation and remodeling caused by immunological reactions to various antigens on tissue surfaces. Due to their anatomical location, vascular endothelial cells are the final responders to interact with various exogenous factors that come into contact with the epithelial surface, such as pathogen-associated molecular patterns (PAMPs) and antigens. Recent studies have shed light on the important roles of endothelial cells in the development and exacerbation of allergic disorders. For instance, endothelial cells have the greatest potential to produce several key molecules that are deeply involved in allergic inflammation, such as periostin and thymus and activation-regulated chemokine (TARC/CCL17). Additionally, endothelial cells were recently shown to be important functional targets for IL-33--an essential regulator of allergic inflammation. Notably, almost all endothelial cell responses and functions involved in allergic inflammation are not suppressed by corticosteroids. These corticosteroid-refractory endothelial cell responses and functions include TNF-α-associated angiogenesis, leukocyte adhesion, IL-33-mediated responses and periostin and TARC production. Therefore, these unique responses and functions of endothelial cells may be critically involved in the pathogenesis of various allergic disorders, especially their refractory processes. Here, we review recent studies, including ours, which have elucidated previously unknown pathophysiological roles of vascular endothelial cells in allergic inflammation and discuss the possibility of endothelium-targeted therapy for allergic disorders.

  17. Conserved steroid hormone homology converges on nuclear factor κB to modulate inflammation in asthma.

    Science.gov (United States)

    Payne, Asha S; Freishtat, Robert J

    2012-01-01

    Asthma is a complex, multifactorial disease comprising multiple different subtypes, rather than a single disease entity, yet it has a consistent clinical phenotype: recurring episodes of chest tightness, wheezing, and difficulty breathing (Pediatr Pulmonol Suppl. 1997;15:9-12). Despite the complex pathogenesis of asthma, steroid hormones (eg, glucocorticoids) are ubiquitous in the short-term and long-term management of all types of asthma. Overall, steroid hormones are a class of widely relevant, biologically active compounds originating from cholesterol and altered in a stepwise fashion, but maintain a basic 17-carbon, 4-ring structure. Steroids are lipophilic molecules that diffuse readily through cell membranes to directly and/or indirectly affect gene transcription. In addition, they use rapid, nongenomic actions to affect cellular products. Steroid hormones comprise several groups (including glucocorticoids, sex steroid hormones, and secosteroids) with critical divergent biological and physiological functions relevant to health and disease. However, the conserved homology of steroid hormone molecules, receptors, and signaling pathways suggests that each of these is part of a dynamic system of hormone interaction, likely involving an overlap of downstream signaling mechanisms. Therefore, we will review the similarities and differences of these 3 groups of steroid hormones (ie, glucocorticoids, sex steroid hormones, and secosteroids), identifying nuclear factor κB as a common inflammatory mediator. Despite our understanding of the impact of individual steroids (eg, glucocorticoids, sex steroids and secosteroids) on asthma, research has yet to explain the interplay of the dynamic system in which these hormones function. To do so, there needs to be a better understanding of the interplay of classic, nonclassic, and nongenomic steroid hormone functions. However, clues from the conserved homology steroid hormone structure and function and signaling pathways offer

  18. Mast cells modulate acute toxoplasmosis in murine models.

    Science.gov (United States)

    Huang, Bo; Huang, Shiguang; Chen, Ying; Zheng, Huanqin; Shen, Jilong; Lun, Zhao-Rong; Wang, Yong; Kasper, Lloyd H; Lu, Fangli

    2013-01-01

    The role of mast cells (MCs) in Toxoplasma gondii infection is poorly known. Kunming outbred mice were infected intraperitoneally with RH strain T. gondii, either treated with compound 48/80 (C48/80, MC activator) or disodium cromoglycate (DSCG, MC inhibitor). Compared with infected controls, infected mice treated with C48/80 exhibited significantly increased inflammation in the liver (P DSCG had significantly decreased tissue lesions (P DSCG. These findings suggest that mediators associated with the MC activation may play an important role in modulating acute inflammatory pathogenesis and parasite clearance during T. gondii infection in this strain of mice. Thus, MC activation/inhibition mechanisms are potential novel targets for the prevention and control of T. gondii infection. PMID:24146978

  19. Activated protein C modulates the proinflammatory activity of dendritic cells

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    Matsumoto T

    2015-05-01

    Full Text Available Takahiro Matsumoto,1,2* Yuki Matsushima,1* Masaaki Toda,1 Ziaurahman Roeen,1 Corina N D'Alessandro-Gabazza,1,5 Josephine A Hinneh,1 Etsuko Harada,1,3 Taro Yasuma,4 Yutaka Yano,4 Masahito Urawa,1,5 Tetsu Kobayashi,5 Osamu Taguchi,5 Esteban C Gabazza1 1Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, 2BONAC Corporation, BIO Factory 4F, Fukuoka, 3Iwade Research Institute of Mycology, 4Department of Endocrinology, Diabetes and Metabolism, 5Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan *These authors contributed equally to this work Background: Previous studies have demonstrated the beneficial activity of activated protein C in allergic diseases including bronchial asthma and rhinitis. However, the exact mechanism of action of activated protein C in allergies is unclear. In this study, we hypothesized that pharmacological doses of activated protein C can modulate allergic inflammation by inhibiting dendritic cells. Materials and methods: Dendritic cells were prepared using murine bone marrow progenitor cells and human peripheral monocytes. Bronchial asthma was induced in mice that received intratracheal instillation of ovalbumin-pulsed dendritic cells. Results: Activated protein C significantly increased the differentiation of tolerogenic plasmacytoid dendritic cells and the secretion of type I interferons, but it significantly reduced lipopolysaccharide-mediated maturation and the secretion of inflammatory cytokines in myeloid dendritic cells. Activated protein C also inhibited maturation and the secretion of inflammatory cytokines in monocyte-derived dendritic cells. Activated protein C-treated dendritic cells were less effective when differentiating naïve CD4 T-cells from Th1 or Th2 cells, and the cellular effect of activated protein C was mediated by its receptors. Mice that received adoptive transfer of activated protein C

  20. G Protein-Coupled Receptor 43 Modulates Neutrophil Recruitment during Acute Inflammation

    Science.gov (United States)

    Nicholls, Alyce J.; Oliveira, Ana Carolina; Mason, Linda J.; Binge, Lauren; Mackay, Charles R.; Wong, Connie H. Y.

    2016-01-01

    Fermentation of dietary fibre in the gut yields large amounts of short chain fatty acids (SCFAs). SCFAs can impart biological responses in cells through their engagement of ‘metabolite-sensing’ G protein-coupled receptors (GPCRs). One of the main SCFA receptors, GPR43, is highly expressed by neutrophils, which suggests that the actions of GPR43 and dietary fibre intake may affect neutrophil recruitment during inflammatory responses in vivo. Using intravital imaging of the small intestine, we found greater intravascular neutrophil rolling and adhesion in Gpr43−/−mice in response to LPS at 1 h. After 4 h of LPS challenge, the intravascular rolling velocity of GPR43-deficient neutrophils was reduced significantly and increased numbers of neutrophils were found in the lamina propria of Gpr43−/−mice. Additionally, GPR43-deficient leukocytes demonstrated exacerbated migration into the peritoneal cavity following fMLP challenge. The fMLP-induced neutrophil migration was significantly suppressed in wildtype mice that were treated with acetate, but not in Gpr43−/−mice, strongly suggesting a role for SCFAs in modulating neutrophil migration via GPR43. Indeed, neutrophils of no fibre-fed wildtype mice exhibited elevated migratory behaviour compared to normal chow-fed wildtype mice. Interestingly, this elevated migration could also be reproduced through simple transfer of a no fibre microbiota into germ-free mice, suggesting that the composition and function of microbiota stemming from a no fibre diet mediated the changes in neutrophil migration. Therefore, GPR43 and a microbiota composition that allows for SCFA production function to modulate neutrophil recruitment during inflammatory responses. PMID:27658303

  1. Modulation of epidermal transcription circuits in psoriasis: new links between inflammation and hyperproliferation.

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    William R Swindell

    Full Text Available BACKGROUND: Whole-genome expression profiling has been used to characterize molecular-level differences between psoriasis lesions and normal skin. Pathway analysis, however, is complicated by the fact that expression profiles have been derived from bulk skin biopsies with RNA derived from multiple cell types. RESULTS: We analyzed gene expression across a large sample of psoriatic (PP and uninvolved/normal (PN skin biopsies (n = 215 patients. We identified 1975 differentially expressed genes, including 8 associated with psoriasis susceptibility loci. To facilitate pathway analysis, PP versus PN differences in gene expression were analyzed with respect to 235 gene modules, each containing genes with a similar expression pattern in keratinocytes and epidermis. We identified 30 differentially expressed modules (DEMs biased towards PP-increased or PP-decreased expression. These DEMs were associated with regulatory axes involving cytokines (e.g., IFN-γ, IL-17A, TNF-α, transcription factors (e.g., STAT1, NF-κB, E2F, RUNX1 and chromatin modifiers (SETDB1. We identified an interferon-induced DEM with genes encoding anti-viral proteins (designated "STAT1-57", which was activated in psoriatic epidermis but repressed following biologic therapy. Genes within this DEM shared a motif near the transcription start site resembling the interferon-stimulated response element (ISRE. CONCLUSIONS: We analyzed a large patient cohort and developed a new approach for delineating epidermis-specific pathways and regulatory mechanisms that underlie altered gene expression in psoriasis. Our findings highlight previously unrecognized "transcription circuits" that can provide targets for development of non-systemic therapies.

  2. Lung function and airway inflammation monitoring after hematopoietic stem cell transplantation.

    OpenAIRE

    Moermans, Catherine; Poulet, Christophe; Henket, Monique; Bonnet, Christophe; WILLEMS, Evelyne; Baron, Frédéric; Beguin, Yves; Louis, Renaud

    2013-01-01

    Background Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the context of hematopoietic stem cell transplantation (HSCT). Methods We monitored lung function in 182 patients who underwent HSCT and measured airway inflammation by sputum induction in 80 of them. We prospectively measured FEV1, FVC, DLCO, KCO, TLC, RV, exhaled nitric oxide (FeNO) as ...

  3. The Neuroprotective Effect of Rapamycin as a Modulator of the mTOR-NF-κB Axis during Retinal Inflammation.

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    Tomohiro Okamoto

    Full Text Available The determination of the molecular mechanism underlying retinal pathogenesis and visual dysfunction during innate inflammation, and the treatment effect of rapamycin thereon.The endotoxin-induced uveitis and retinitis mouse model was established by injecting lipopolysaccharide. The mice were subsequently treated with rapamycin, a mammalian target of rapamycin (mTOR inhibitor. The rhodopsin mRNA and protein expression level in the retina and the photoreceptor outer segment (OS length in immunohistochemical stainings were measured, and visual function was recorded by electroretinography. Inflammatory cytokines, their related molecules, mTOR, and LC3 levels were measured by real-time PCR and/or immunoblotting. Leukocyte adhesion during inflammation was analyzed using concanavalin A lectin.The post-transcriptional reduction in the visual pigment of rod photoreceptor cells, rhodopsin, OS shortening, and rod photoreceptor cell dysfunction during inflammation were suppressed by rapamycin. Activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and induction of inflammatory cytokines, such as interleukin-6 (IL-6 and monocyte chemoattractant protein-1 (MCP-1, and the activation of the downstream signaling protein, signal transducer and activator of transcription 3 (STAT3, which reduces rhodopsin in the retina during inflammation, were attenuated by rapamycin. Increased leukocyte adhesion was also attenuated by rapamycin. Interestingly, although mTOR activation was observed after NF-κB activation, mTOR inhibition suppressed NF-κB activation at the early phase, indicating that the basal level of activated mTOR was sufficient to activate NF-κB in the retina. In addition, the inhibition of NF-κB suppressed mTOR activation, suggesting a positive feedback loop of mTOR and NF-κB during inflammation. The ratio of LC3II to LC3I, which reflects autophagy induction, was not changed by inflammation but was increased by rapamycin

  4. SIRT1 inactivation induces inflammation through the dysregulation of autophagy in human THP-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Takeda-Watanabe, Ai; Kitada, Munehiro; Kanasaki, Keizo [Diabetology and Endocrinology, Kanazawa Medical University, Kahoku-Gun, Ishikawa (Japan); Koya, Daisuke, E-mail: koya0516@kanazawa-med.ac.jp [Diabetology and Endocrinology, Kanazawa Medical University, Kahoku-Gun, Ishikawa (Japan)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer SIRT1 inactivation decreases autophagy in THP-1 cell. Black-Right-Pointing-Pointer Inhibition of autophagy induces inflammation. Black-Right-Pointing-Pointer SIRT1 inactivation induces inflammation through NF-{kappa}B activation. Black-Right-Pointing-Pointer The p62/Sqstm1 accumulation by impairment of autophagy is related to NF-{kappa}B activation. Black-Right-Pointing-Pointer SIRT1 inactivation is involved in the activation of mTOR and decreased AMPK activation. -- Abstract: Inflammation plays a crucial role in atherosclerosis. Monocytes/macrophages are some of the cells involved in the inflammatory process in atherogenesis. Autophagy exerts a protective effect against cellular stresses like inflammation, and it is regulated by nutrient-sensing pathways. The nutrient-sensing pathway includes SIRT1, a NAD{sup +}-dependent histone deacetylase, which is implicated in the regulation of a variety of cellular processes including inflammation and autophagy. The mechanism through which the dysfunction of SIRT1 contributes to the regulation of inflammation in relation to autophagy in monocytes/macrophages is unclear. In the present study, we demonstrate that treatment with 2-[(2-Hydroxynaphthalen-1-ylmethylene)amino]-N-(1-phenethyl)benzamide (Sirtinol), a chemical inhibitor of SIRT1, induces the overexpression of inflammation-related genes such as tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-6 through nuclear factor (NF)-{kappa}B signaling activation, which is associated with autophagy dysfunction, as shown through p62/Sqstm1 accumulation and decreased expression of light chain (LC) 3 II in THP-1 cells. The autophagy inhibitor, 3-methyladenine, also induces inflammation-related NF-{kappa}B activation. In p62/Sqstm1 knockdown cells, Sirtinol-induced inflammation through NF-{kappa}B activation is blocked. In addition, inhibition of SIRT1 is involved in the activation of the mammalian target of rapamycin (mTOR) pathway and

  5. Bone marrow-derived mesenchymal stromal cells inhibit Th2-mediated allergic airways inflammation in mice.

    Science.gov (United States)

    Goodwin, Meagan; Sueblinvong, Viranuj; Eisenhauer, Philip; Ziats, Nicholas P; LeClair, Laurie; Poynter, Matthew E; Steele, Chad; Rincon, Mercedes; Weiss, Daniel J

    2011-07-01

    Bone marrow-derived mesenchymal stromal cells (BMSCs) mitigate inflammation in mouse models of acute lung injury. However, specific mechanisms of BMSC actions on CD4 T lymphocyte-mediated inflammation in vivo remain poorly understood. Limited data suggests promotion of Th2 phenotype in models of Th1-mediated diseases. However, whether this might alleviate or worsen Th2-mediated diseases such as allergic asthma is unknown. To ascertain the effects of systemic administration of BMSCs in a mouse model of Th2-mediated allergic airways inflammation, ovalbumin (OVA)-induced allergic airways inflammation was induced in wild-type C57BL/6 and BALB/c mice as well as in interferon-γ (IFNγ) receptor null mice. Effects of systemic administration during antigen sensitization of either syngeneic or allogeneic BMSC on airways hyperreactivity, lung inflammation, antigen-specific CD4 T lymphocytes, and serum immunoglobulins were assessed. Both syngeneic and allogeneic BMSCs inhibited airways hyperreactivity and lung inflammation through a mechanism partly dependent on IFNγ. However, contrary to existing data, BMSCs did not affect antigen-specific CD4 T lymphocyte proliferation but rather promoted Th1 phenotype in vivo as assessed by both OVA-specific CD4 T lymphocyte cytokine production and OVA-specific circulating immunoglobulins. BMSCs treated to prevent release of soluble mediators and a control cell population of primary dermal skin fibroblasts only partly mimicked the BMSC effects and in some cases worsened inflammation. In conclusion, BMSCs inhibit Th2-mediated allergic airways inflammation by influencing antigen-specific CD4 T lymphocyte differentiation. Promotion of a Th1 phenotype in antigen-specific CD4 T lymphocytes by BMSCs is sufficient to inhibit Th2-mediated allergic airways inflammation through an IFNγ-dependent process. PMID:21544902

  6. Adipose-Derived Stem Cells Ameliorate Allergic Airway Inflammation by Inducing Regulatory T Cells in a Mouse Model of Asthma

    OpenAIRE

    Kyu-Sup Cho; Mi-Kyung Park; Shin-Ae Kang; Hee-Young Park; Sung-Lyong Hong; Hye-Kyung Park; Hak-Sun Yu; Hwan-Jung Roh

    2014-01-01

    Although several studies have demonstrated that mesenchymal stem cells derived from adipose tissue (ASCs) can ameliorate allergic airway inflammation, the immunomodulatory mechanism of ASCs remains unclear. In this study, we investigated whether regulatory T cells (Tregs) induction is a potential mechanism in immunomodulatory effects of ASCs on allergic airway disease and how these induced Tregs orchestrate allergic inflammation. Intravenous administration of ASCs significantly reduced allerg...

  7. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian

    2012-01-01

    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  8. Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells

    Science.gov (United States)

    Shenoda, Botros B.; Ajit, Seena K.

    2016-01-01

    Exosome-mediated signaling is important in mediating the inflammatory response. To exert their biological or pathophysiological functions in the recipient cells, exosomes deliver a diverse array of biomacromolecules including long and short coding and non-coding RNAs, proteins, and lipids. Exosomes secreted by antigen-presenting cells can confer therapeutic benefits by attenuating or stimulating the immune response. Exosomes play a crucial role in carrying and presenting functional major histocompatibility peptide complexes to modulate antigen-specific T cell responses. Exosomes from Dendritic Cells (DCs) can activate T and B cells and have been explored for their immunostimulatory properties in cancer therapy. The immunosuppressive properties of exosomes derived from macrophages and DCs can reduce inflammation in animal models for several inflammatory disorders. This review focuses on the protective role of exosomes in attenuating inflammation or augmenting immune response, emphasizing studies on exosomes derived from DCs and macrophages. PMID:27660518

  9. Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells.

    Science.gov (United States)

    Shenoda, Botros B; Ajit, Seena K

    2016-01-01

    Exosome-mediated signaling is important in mediating the inflammatory response. To exert their biological or pathophysiological functions in the recipient cells, exosomes deliver a diverse array of biomacromolecules including long and short coding and non-coding RNAs, proteins, and lipids. Exosomes secreted by antigen-presenting cells can confer therapeutic benefits by attenuating or stimulating the immune response. Exosomes play a crucial role in carrying and presenting functional major histocompatibility peptide complexes to modulate antigen-specific T cell responses. Exosomes from Dendritic Cells (DCs) can activate T and B cells and have been explored for their immunostimulatory properties in cancer therapy. The immunosuppressive properties of exosomes derived from macrophages and DCs can reduce inflammation in animal models for several inflammatory disorders. This review focuses on the protective role of exosomes in attenuating inflammation or augmenting immune response, emphasizing studies on exosomes derived from DCs and macrophages. PMID:27660518

  10. Nutritional strategies to modulate inflammation and oxidative stress pathways via activation of the master antioxidant switch Nrf2.

    Science.gov (United States)

    Cardozo, Ludmila F M F; Pedruzzi, Liliana M; Stenvinkel, Peter; Stockler-Pinto, Milena B; Daleprane, Julio B; Leite, Maurilo; Mafra, Denise

    2013-08-01

    The nuclear factor E2-related factor 2 (Nrf2) plays an important role in cellular protection against cancer, renal, pulmonary, cardiovascular and neurodegenerative diseases where oxidative stress and inflammation are common conditions. The Nrf2 regulates the expression of detoxifying enzymes by recognizing the human Antioxidant Response Element (ARE) binding site and it can regulate antioxidant and anti-inflammatory cellular responses, playing an important protective role on the development of the diseases. Studies designed to investigate how effective Nrf2 activators or modulators are need to be initiated. Several recent studies have shown that nutritional compounds can modulate the activation of Nrf2-Keap1 system. This review aims to discuss some of the key nutritional compounds that promote the activation of Nrf2, which may have impact on the human health. PMID:23643732

  11. Pattern Recognition Receptors as modulators of Mesenchymal Stem Cells

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    Olga eDelaRosa

    2012-07-01

    Full Text Available Mesenchymal stem cells (MSCs have differentiation and immunomodulatory properties that make them interesting tools for the treatment of degenerative disorders, allograft rejection or inflammatory and autoimmune diseases. Biological properties of MSCs can be modulated by the inflammatory microenvironment they face at the sites of injury or inflammation. Indeed, MSCs do not constitutively exert their immunomodulating properties but have to be primed by inflammatory mediators released from immune cells and inflamed tissue. A polarization process, mediated by pattern recognition receptors (PRRs, towards either an anti-inflammatory or a pro-inflammatory phenotype has been described for MSCs. PRRs, including Toll-like receptors (TLRs and NOD-like receptors (NLRs, have been linked to allograft rejection and the perpetuation of chronic inflammatory diseases (e.g. Crohn´s disease, rheumatoid arthritis through the recognition of conserved pathogen-derived components or endogenous ligands (danger signals produced upon injury. Interest in understanding the effects of PRR activation on MSCs has greatly increased in the last few years since MSCs will likely encounter PRRs ligands at sites of injury, and it has been proven that the activation of PRRs in MSCs can modulate their function and therapeutic effect.

  12. Influenza virus-induced lung inflammation was modulated by cigarette smoke exposure in mice.

    Directory of Open Access Journals (Sweden)

    Yan Han

    Full Text Available Although smokers have increased susceptibility and severity of seasonal influenza virus infection, there is no report about the risk of 2009 pandemic H1N1 (pdmH1N1 or avian H9N2 (H9N2/G1 virus infection in smokers. In our study, we used mouse model to investigate the effect of cigarette smoke on pdmH1N1 or H9N2 virus infection. Mice were exposed to cigarette smoke for 21 days and then infected with pdmH1N1 or H9N2 virus. Control mice were exposed to air in parallel. We found that cigarette smoke exposure alone significantly upregulated the lung inflammation. Such prior cigarette smoke exposure significantly reduced the disease severity of subsequent pdmH1N1 or H9N2 virus infection. For pdmH1N1 infection, cigarette smoke exposed mice had significantly lower mortality than the control mice, possibly due to the significantly decreased production of inflammatory cytokines and chemokines. Similarly, after H9N2 infection, cigarette smoke exposed mice displayed significantly less weight loss, which might be attributed to lower cytokines and chemokines production, less macrophages, neutrophils, CD4+ and CD8+ T cells infiltration and reduced lung damage compared to the control mice. To further investigate the underlying mechanism, we used nicotine to mimic the effect of cigarette smoke both in vitro and in vivo. Pre-treating the primary human macrophages with nicotine for 72 h significantly decreased their expression of cytokines and chemokines after pdmH1N1 or H9N2 infection. The mice subcutaneously and continuously treated with nicotine displayed significantly less weight loss and lower inflammatory response than the control mice upon pdmH1N1 or H9N2 infection. Moreover, α7 nicotinic acetylcholine receptor knockout mice had more body weight loss than wild-type mice after cigarette smoke exposure and H9N2 infection. Our study provided the first evidence that the pathogenicity of both pdmH1N1 and H9N2 viruses was alleviated in cigarette smoke exposed

  13. Helicobacter pylori coinfection is a confounder, modulating mucosal inflammation in oral submucous fibrosis

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    Rajendran R

    2009-01-01

    Full Text Available The oral cavity has been considered a potential reservoir for Helicobacter pylori (H pylori , from where the organism causes recurrent gastric infections. Aim: With this case-control study we tried to evaluate the role of H pylori in the etiology of mucosal inflammation, a condition that compounds the morbid state associated with oral submucous fibrosis (OSF. Materials and Methods : Subjects ( n = 150 were selected following institutional regulations on sample collection and grouped into test cases and positive and negative controls based on the presence of mucosal fibrosis and inflammation. The negative controls had none of the clinical signs. All patients underwent an oral examination as well as tests to assess oral hygiene/periodontal disease status; a rapid urease test (RUT of plaque samples was also done to estimate the H pylori bacterial load. We used univariate and mutivariate logistic regression for statistical analysis of the data and calculated the odds ratios to assess the risk posed by the different variables. Results : The RUT results differed significantly between the groups, reflecting the variations in the bacterial loads in each category. The test was positive in 52% in the positive controls (where nonspecific inflammation of oral mucosa was seen unassociated with fibrosis, in 46% of the test cases, and in 18% of the negative controls (healthy volunteers (χ2 = 13.887; P < 0.01. A positive correlation was seen between the oral hygiene/periodontal disease indices and RUT reactivity in all the three groups. Conclusions: The contribution of the H pylori in dental plaque to mucosal inflammation and periodontal disease was significant. Logistic regression analysis showed gastrointestinal disease and poor oral hygiene as being the greatest risk factors for bacterial colonization, irrespective of the subject groups. A positive correlation exists between RUT reactivity and the frequency of mucosal inflammation.

  14. Systemic interleukin-2 administration improves lung function and modulates chorioamnionitis-induced pulmonary inflammation in the ovine fetus.

    Science.gov (United States)

    Willems, Monique G M; Ophelders, Daan R M G; Nikiforou, Maria; Jellema, Reint K; Butz, Anke; Delhaas, Tammo; Kramer, Boris W; Wolfs, Tim G A M

    2016-01-01

    Chorioamnionitis, an inflammatory reaction of the fetal membranes to microbes, is an important cause of preterm birth and associated with inflammation-driven lung injury. However, inflammation in utero overcomes immaturity of the premature lung by inducing surfactant lipids and lung gas volume. Previously, we found that lipopolysaccharide (LPS)-induced chorioamnionitis resulted in pulmonary inflammation with increased effector T cells and decreased regulatory T cell (Treg) numbers. Because Tregs are crucial for immune regulation, we assessed the effects of interleukin (IL)-2-driven selective Treg expansion on the fetal lung in an ovine chorioamnionitis model. Instrumented fetuses received systemic prophylactic IL-2 treatment [118 days gestational age (dGA)] with or without subsequent exposure to intra-amniotic LPS (122 dGA). Following delivery at 129 dGA (term 147 dGA), pulmonary and systemic inflammation, morphological changes, lung gas volume, and phospholipid concentration were assessed. IL-2 pretreatment increased the FoxP3(+)/CD3(+) ratio, which was associated with reduced CD3-positive cells in the fetal lungs of LPS-exposed animals. Prophylactic IL-2 treatment did not prevent pulmonary accumulation of myeloperoxidase- and PU.1-positive cells or elevation of bronchoalveolar lavage fluid IL-8 and systemic IL-6 concentrations in LPS-exposed animals. Unexpectedly, IL-2 treatment improved fetal lung function of control lambs as indicated by increased disaturated phospholipids and improved lung gas volume. In conclusion, systemic IL-2 treatment in utero preferentially expanded Tregs and improved lung gas volume and disaturated phospholipids. These beneficial effects on lung function were maintained despite the moderate immunomodulatory effects of prophylactic IL-2 in the course of chorioamnionitis. PMID:26519206

  15. Blockade of Airway Inflammation by Kaempferol via Disturbing Tyk-STAT Signaling in Airway Epithelial Cells and in Asthmatic Mice

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    Ju-Hyun Gong

    2013-01-01

    Full Text Available Asthma is characterized by bronchial inflammation causing increased airway hyperresponsiveness and eosinophilia. The interaction between airway epithelium and inflammatory mediators plays a key role in the asthmatic pathogenesis. The in vitro study elucidated inhibitory effects of kaempferol, a flavonoid found in apples and many berries, on inflammation in human airway epithelial BEAS-2B cells. Nontoxic kaempferol at ≤20 μM suppressed the LPS-induced IL-8 production through the TLR4 activation, inhibiting eotaxin-1 induction. The in vivo study explored the demoting effects of kaempferol on asthmatic inflammation in BALB/c mice sensitized with ovalbumin (OVA. Mouse macrophage inflammatory protein-2 production and CXCR2 expression were upregulated in OVA-challenged mice, which was attenuated by oral administration of ≥10 mg/kg kaempferol. Kaempferol allayed the airway tissue levels of eotaxin-1 and eotaxin receptor CCR3 enhanced by OVA challenge. This study further explored the blockade of Tyk-STAT signaling by kaempferol in both LPS-stimulated BEAS-2B cells and OVA-challenged mice. LPS activated Tyk2 responsible for eotaxin-1 induction, while kaempferol dose-dependently inhibited LPS- or IL-8-inflamed Tyk2 activation. Similar inhibition of Tyk2 activation by kaempferol was observed in OVA-induced mice. Additionally, LPS stimulated the activation of STAT1/3 signaling concomitant with downregulated expression of Tyk-inhibiting SOCS3. In contrast, kaempferol encumbered STAT1/3 signaling with restoration of SOCS3 expression. Consistently, oral administration of kaempferol blocked STAT3 transactivation elevated by OVA challenge. These results demonstrate that kaempferol alleviated airway inflammation through modulating Tyk2-STAT1/3 signaling responsive to IL-8 in endotoxin-exposed airway epithelium and in asthmatic mice. Therefore, kaempferol may be a therapeutic agent targeting asthmatic diseases.

  16. Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 Cells

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    Sabrina Gruber

    2016-03-01

    Full Text Available Atherosclerosis is initiated and sustained by hypercholesterolemia, which results in the generation of oxidized LDL (OxLDL and other metabolic byproducts that trigger inflammation. Specific immune responses have been shown to modulate the inflammatory response during atherogenesis. The sialic acid-binding immunoglobulin-like lectin G (Siglec-G is a negative regulator of the functions of several immune cells, including myeloid cells and B-1 cells. Here, we show that deficiency of Siglec-G in atherosclerosis-prone mice inhibits plaque formation and diet-induced hepatic inflammation. We further demonstrate that selective deficiency of Siglec-G in B cells alone is sufficient to mediate these effects. Levels of B-1 cell-derived natural IgM with specificity for OxLDL were significantly increased in the plasma and peritoneal cavity of Siglec-G-deficient mice. Consistent with the neutralizing functions of OxLDL-specific IgM, Siglec-G-deficient mice were protected from OxLDL-induced sterile inflammation. Thus, Siglec-G promotes atherosclerosis and hepatic inflammation by suppressing protective anti-inflammatory effector functions of B cells.

  17. Parasitic nematode-induced CD4+Foxp3+T cells can ameliorate allergic airway inflammation.

    Directory of Open Access Journals (Sweden)

    Shin Ae Kang

    2014-12-01

    Full Text Available The recruitment of CD4+CD25+Foxp3+T (Treg cells is one of the most important mechanisms by which parasites down-regulate the immune system.We compared the effects of Treg cells from Trichinella spiralis-infected mice and uninfected mice on experimental allergic airway inflammation in order to understand the functions of parasite-induced Treg cells. After four weeks of T. spiralis infection, we isolated Foxp3-GFP-expressing cells from transgenic mice using a cell sorter. We injected CD4+Foxp3+ cells from T. spiralis-infected [Inf(+Foxp3+] or uninfected [Inf(-Foxp3+] mice into the tail veins of C57BL/6 mice before the induction of inflammation or during inflammation. Inflammation was induced by ovalbumin (OVA-alum sensitization and OVA challenge. The concentrations of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and the levels of OVA-specific IgE and IgG1 in the serum were lower in mice that received intravenous application of Inf(+Foxp3+ cells [IV(inf:+(+ group] than in control mice. Some features of allergic airway inflammation were ameliorated by the intravenous application of Inf(-Foxp3+ cells [IV(inf:+(- group], but the effects were less distinct than those observed in the IV(inf:+(+ group. We found that Inf(+Foxp3+ cells migrated to inflammation sites in the lung and expressed higher levels of Treg-cell homing receptors (CCR5 and CCR9 and activation markers (Klrg1, Capg, GARP, Gzmb, OX40 than did Inf(-Foxp3+ cells.T. spiralis infection promotes the proliferation and functional activation of Treg cells. Parasite-induced Treg cells migrate to the inflammation site and suppress immune responses more effectively than non-parasite-induced Treg cells. The adoptive transfer of Inf(+Foxp3+ cells is an effective method for the treatment and prevention of allergic airway diseases in mice and is a promising therapeutic approach for the treatment of allergic airway diseases.

  18. Relation of circulating T cell profiles to airway inflammation and asthma control in asthmatic pregnancy.

    Science.gov (United States)

    Eszes, N; Bohács, A; Cseh, A; Toldi, G; Bikov, A; Ivancsó, I; Müller, V; Horváth, I; Rigó, J; Vásárhelyi, B; Losonczy, Gy; Tamási, L

    2012-09-01

    Asthmatic inflammation during pregnancy poses a risk for maternal and fetal morbidities. Circulating T cell immune phenotype is known to correlate with airway inflammation (detectable by fractional concentration of nitric oxide present in exhaled breath (FENO)) in non-pregnant allergic asthmatics. The aim of this study was to assess the relationship of peripheral T cell phenotype to FENO and clinical variables of asthma during pregnancy.We examined 22 pregnant women with allergic asthma in the 2nd/3rd trimester. The prevalence of Th1, Th2, regulatory T (Treg) and natural killer (NK) cell subsets was identified with flow cytometry using cell-specific markers. FENO, Asthma Control Test (ACT) total score and lung function were evaluated.Peripheral blood Th1, Th2, Treg, and NK cell prevalence were not significantly correlated to airway inflammation assessed by FENO in asthmatic pregnant women (all cells p > 0.05; study power > 75%). However, an inverse correlation was detected between Th2 cell prevalence and ACT total scores (p = 0.03) in asthmatic pregnancy.Blunted relationship between T cell profile and airway inflammation may be the result of pregnancy induced immune tolerance in asthmatic pregnancy. On the other hand, increased Th2 response impairs disease control that supports direct relationship between symptoms and cellular mechanisms of asthma during pregnancy. PMID:22982718

  19. Effect of Cocoa and Its Flavonoids on Biomarkers of Inflammation: Studies of Cell Culture, Animals and Humans.

    Science.gov (United States)

    Goya, Luis; Martín, María Ángeles; Sarriá, Beatriz; Ramos, Sonia; Mateos, Raquel; Bravo, Laura

    2016-01-01

    Chronic inflammation has been identified as a necessary step to mediate atherosclerosis and cardiovascular disease and as a relevant stage in the onset and progression of several types of cancer. Considerable attention has recently been focused on the identification of dietary bioactive compounds with anti-inflammatory activities as an alternative natural source for prevention of inflammation-associated diseases. The remarkable capacity of cocoa flavanols as antioxidants, as well as to modulate signaling pathways involved in cellular processes, such as inflammation, metabolism and proliferation, has encouraged research on this type of polyphenols as useful bioactive compounds for nutritional prevention of cardiovascular disease and cancer. Data from numerous studies suggest that cocoa and cocoa-derived flavanols can effectively modify the inflammatory process, and thus potentially provide a benefit to individuals with elevated risk factors for atherosclerosis/cardiovascular pathology and cancer. The present overview will focus on the most recent findings about the effects of cocoa, its main constituents and cocoa derivatives on selected biomarkers of the inflammatory process in cell culture, animal models and human cohorts. PMID:27070643

  20. Effect of Cocoa and Its Flavonoids on Biomarkers of Inflammation: Studies of Cell Culture, Animals and Humans

    Science.gov (United States)

    Goya, Luis; Martín, María Ángeles; Sarriá, Beatriz; Ramos, Sonia; Mateos, Raquel; Bravo, Laura

    2016-01-01

    Chronic inflammation has been identified as a necessary step to mediate atherosclerosis and cardiovascular disease and as a relevant stage in the onset and progression of several types of cancer. Considerable attention has recently been focused on the identification of dietary bioactive compounds with anti-inflammatory activities as an alternative natural source for prevention of inflammation-associated diseases. The remarkable capacity of cocoa flavanols as antioxidants, as well as to modulate signaling pathways involved in cellular processes, such as inflammation, metabolism and proliferation, has encouraged research on this type of polyphenols as useful bioactive compounds for nutritional prevention of cardiovascular disease and cancer. Data from numerous studies suggest that cocoa and cocoa-derived flavanols can effectively modify the inflammatory process, and thus potentially provide a benefit to individuals with elevated risk factors for atherosclerosis/cardiovascular pathology and cancer. The present overview will focus on the most recent findings about the effects of cocoa, its main constituents and cocoa derivatives on selected biomarkers of the inflammatory process in cell culture, animal models and human cohorts. PMID:27070643

  1. Probiotics modulate intestinal expression of nuclear receptor and provide counter-regulatory signals to inflammation-driven adipose tissue activation.

    Directory of Open Access Journals (Sweden)

    Andrea Mencarelli

    Full Text Available BACKGROUND: Adipocytes from mesenteric white adipose tissue amplify the inflammatory response and participate in inflammation-driven immune dysfunction in Crohn's disease by releasing proinflammatory mediators. Peroxisome proliferator-activated receptors (PPAR-α and -γ, pregnane x receptor (PXR, farnesoid x receptor (FXR and liver x-receptor (LXR are ligand-activated nuclear receptor that provide counter-regulatory signals to dysregulated immunity and modulates adipose tissue. AIMS: To investigate the expression and function of nuclear receptors in intestinal and adipose tissues in a rodent model of colitis and mesenteric fat from Crohn's patients and to investigate their modulation by probiotics. METHODS: Colitis was induced by TNBS administration. Mice were administered vehicle or VSL#3, daily for 10 days. Abdominal fat explants obtained at surgery from five Crohn's disease patients and five patients with colon cancer were cultured with VSL#3 medium. RESULTS: Probiotic administration attenuated development of signs and symptoms of colitis, reduced colonic expression of TNFα, IL-6 and IFNγ and reserved colonic downregulation of PPARγ, PXR and FXR caused by TNBS. Mesenteric fat depots isolated from TNBS-treated animals had increased expression of inflammatory mediators along with PPARγ, FXR, leptin and adiponectin. These changes were prevented by VSL#3. Creeping fat and mesenteric adipose tissue from Crohn's patients showed a differential expression of PPARγ and FXR with both tissue expressing high levels of leptin. Exposure of these tissues to VSL#3 medium abrogates leptin release. CONCLUSIONS: Mesenteric adipose tissue from rodent colitis and Crohn's disease is metabolically active and shows inflammation-driven regulation of PPARγ, FXR and leptin. Probiotics correct the inflammation-driven metabolic dysfunction.

  2. Prostaglandin E₂ constrains systemic inflammation through an innate lymphoid cell-IL-22 axis.

    Science.gov (United States)

    Duffin, Rodger; O'Connor, Richard A; Crittenden, Siobhan; Forster, Thorsten; Yu, Cunjing; Zheng, Xiaozhong; Smyth, Danielle; Robb, Calum T; Rossi, Fiona; Skouras, Christos; Tang, Shaohui; Richards, James; Pellicoro, Antonella; Weller, Richard B; Breyer, Richard M; Mole, Damian J; Iredale, John P; Anderton, Stephen M; Narumiya, Shuh; Maizels, Rick M; Ghazal, Peter; Howie, Sarah E; Rossi, Adriano G; Yao, Chengcan

    2016-03-18

    Systemic inflammation, which results from the massive release of proinflammatory molecules into the circulatory system, is a major risk factor for severe illness, but the precise mechanisms underlying its control are not fully understood. We observed that prostaglandin E2 (PGE2), through its receptor EP4, is down-regulated in human systemic inflammatory disease. Mice with reduced PGE2 synthesis develop systemic inflammation, associated with translocation of gut bacteria, which can be prevented by treatment with EP4 agonists. Mechanistically, we demonstrate that PGE2-EP4 signaling acts directly on type 3 innate lymphoid cells (ILCs), promoting their homeostasis and driving them to produce interleukin-22 (IL-22). Disruption of the ILC-IL-22 axis impairs PGE2-mediated inhibition of systemic inflammation. Hence, the ILC-IL-22 axis is essential in protecting against gut barrier dysfunction, enabling PGE2-EP4 signaling to impede systemic inflammation.

  3. Notch Signaling Contributes to Liver Inflammation by Regulation of Interleukin-22-Producing Cells in Hepatitis B Virus Infection

    Science.gov (United States)

    Wei, Xin; Wang, Jiu-Ping; Hao, Chun-Qiu; Yang, Xiao-Fei; Wang, Lin-Xu; Huang, Chang-Xing; Bai, Xue-Fan; Lian, Jian-Qi; Zhang, Ye

    2016-01-01

    The mechanism of hepatitis B virus (HBV) induced liver inflammation is not fully elucidated. Notch signaling augmented interleukin (IL)-22 secretion in CD4+ T cells, and Notch-IL-22 axis fine-tuned inflammatory response. We previously demonstrated a proinflammatory role of IL-22 in HBV infection. Thus, in this study, we analyzed the role of Notch in development of IL-22-producing cells in HBV infection by inhibition of Notch signaling using γ-secretase inhibitor DAPT in both hydrodynamic induced HBV-infected mouse model and in peripheral blood cells isolated from patients with HBV infection. mRNA expressions of Notch1 and Notch2 were significantly increased in livers and CD4+ T cells upon HBV infection. Inhibition of Notch signaling in vivo leaded to the reduction in NKp46+ innate lymphoid cells 22 (ILC22) and lymphoid tissue inducer 4 (LTi4) cells in the liver. This process was accompanied by downregulating the expressions of IL-22 and related proinflammatory cytokines and chemokines in the liver, as well as blocking the recruitment of antigen-non-specific inflammatory cells into the liver and subsequent liver injury, but did not affect HBV antigens production and IL-22 secretion in the serum. Furthermore, IL-22 production in HBV non-specific cultured CD4+ T cells, but not HBV-specific CD4+ T cells, was reduced in response to in vitro inhibition of Notch signaling. In conclusion, Notch siganling appears to be an important mediator of the liver inflammation by modulating hepatic ILC22. The potential proinflammatory effect of Notch-mediated ILC22 may be significant for the development of new therapeutic approaches for treatment of hepatitis B.

  4. Modulation of visceral pain and inflammation by protease-activated receptors

    OpenAIRE

    Vergnolle, Nathalie

    2004-01-01

    The gastrointestinal (GI) tract is exposed to a large array of proteases, under both physiological and pathophysiological conditions. The discovery of G protein-coupled receptors activated by proteases, the protease-activated receptors (PARs), has highlighted new signaling functions for proteases in the GI tract, particularly in the domains of inflammation and pain mechanisms. Activation of PARs by selective peptidic agonists in the intestine or the pancreas leads to inflammatory events and c...

  5. Perspectives in inflammation, neoplasia, and vascular cell biology

    Energy Technology Data Exchange (ETDEWEB)

    Edgington, T.S.; Ross, R.; Silverstein, S.C.

    1987-01-01

    This book contains 25 selections. Some of the titles are: Characterization of cDNAs for the Human Interleukin-2 Receptor; Regulation of the Epidermal Growth Factor Receptor by Phosphorylation; Endothelial Cell Proteases and Cellular Invasion; Structure and Chromosomal Localization of the Human Lymphotoxin Gene; and Vascular Endothelial Cells in Cell-Mediated Immunity: Adoptive Transfer with In Vitro Conditioned Cells is Genetically Restricted at the Endothelial Cell Barrier.

  6. Annexin A1 and the Resolution of Inflammation: Modulation of Neutrophil Recruitment, Apoptosis, and Clearance

    Science.gov (United States)

    Sugimoto, Michelle Amantéa; Vago, Juliana Priscila; Teixeira, Mauro Martins; Sousa, Lirlândia Pires

    2016-01-01

    Neutrophils (also named polymorphonuclear leukocytes or PMN) are essential components of the immune system, rapidly recruited to sites of inflammation, providing the first line of defense against invading pathogens. Since neutrophils can also cause tissue damage, their fine-tuned regulation at the inflammatory site is required for proper resolution of inflammation. Annexin A1 (AnxA1), also known as lipocortin-1, is an endogenous glucocorticoid-regulated protein, which is able to counterregulate the inflammatory events restoring homeostasis. AnxA1 and its mimetic peptides inhibit neutrophil tissue accumulation by reducing leukocyte infiltration and activating neutrophil apoptosis. AnxA1 also promotes monocyte recruitment and clearance of apoptotic leukocytes by macrophages. More recently, some evidence has suggested the ability of AnxA1 to induce macrophage reprogramming toward a resolving phenotype, resulting in reduced production of proinflammatory cytokines and increased release of immunosuppressive and proresolving molecules. The combination of these mechanisms results in an effective resolution of inflammation, pointing to AnxA1 as a promising tool for the development of new therapeutic strategies to treat inflammatory diseases. PMID:26885535

  7. Static Magnetic Field Attenuates Lipopolysaccharide-Induced Inflammation in Pulp Cells by Affecting Cell Membrane Stability

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    Sung-Chih Hsieh

    2015-01-01

    Full Text Available One of the causes of dental pulpitis is lipopolysaccharide- (LPS- induced inflammatory response. Following pulp tissue inflammation, odontoblasts, dental pulp cells (DPCs, and dental pulp stem cells (DPSCs will activate and repair damaged tissue to maintain homeostasis. However, when LPS infection is too serious, dental repair is impossible and disease may progress to irreversible pulpitis. Therefore, the aim of this study was to examine whether static magnetic field (SMF can attenuate inflammatory response of dental pulp cells challenged with LPS. In methodology, dental pulp cells were isolated from extracted teeth. The population of DPSCs in the cultured DPCs was identified by phenotypes and multilineage differentiation. The effects of 0.4 T SMF on DPCs were observed through MTT assay and fluorescent anisotropy assay. Our results showed that the SMF exposure had no effect on surface markers or multilineage differentiation capability. However, SMF exposure increases cell viability by 15%. In addition, SMF increased cell membrane rigidity which is directly related to higher fluorescent anisotropy. In the LPS-challenged condition, DPCs treated with SMF demonstrated a higher tolerance to LPS-induced inflammatory response when compared to untreated controls. According to these results, we suggest that 0.4 T SMF attenuates LPS-induced inflammatory response to DPCs by changing cell membrane stability.

  8. Adoptive transfer of induced-Treg cells effectively attenuates murine airway allergic inflammation.

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    Wei Xu

    Full Text Available Both nature and induced regulatory T (Treg lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic inflammation, exogenously induced Treg cells were infused into ovalbumin-sensitized mice prior to or during intranasal ovalbumin challenge. The results showed that adoptive transfer of induced Treg cells prior to allergen challenge markedly reduced airway hyperresponsiveness, eosinophil recruitment, mucus hyper-production, airway remodeling, and IgE levels. This effect was associated with increase of Treg cells (CD4(+FoxP3(+ and decrease of dendritic cells in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to the controls. Moreover, adoptive transfer of induced Treg cells during allergen challenge also effectively attenuate airway inflammation and improve airway function, which are comparable to those by natural Treg cell infusion. Therefore, adoptive transfer of in vitro induced Treg cells may be a promising therapeutic approach to prevent and treat severe asthma.

  9. Adoptive transfer of induced-Treg cells effectively attenuates murine airway allergic inflammation.

    Science.gov (United States)

    Xu, Wei; Lan, Qin; Chen, Maogen; Chen, Hui; Zhu, Ning; Zhou, Xiaohui; Wang, Julie; Fan, Huimin; Yan, Chun-Song; Kuang, Jiu-Long; Warburton, David; Togbe, Dieudonnée; Ryffel, Bernhard; Zheng, Song-Guo; Shi, Wei

    2012-01-01

    Both nature and induced regulatory T (Treg) lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic inflammation, exogenously induced Treg cells were infused into ovalbumin-sensitized mice prior to or during intranasal ovalbumin challenge. The results showed that adoptive transfer of induced Treg cells prior to allergen challenge markedly reduced airway hyperresponsiveness, eosinophil recruitment, mucus hyper-production, airway remodeling, and IgE levels. This effect was associated with increase of Treg cells (CD4(+)FoxP3(+)) and decrease of dendritic cells in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to the controls. Moreover, adoptive transfer of induced Treg cells during allergen challenge also effectively attenuate airway inflammation and improve airway function, which are comparable to those by natural Treg cell infusion. Therefore, adoptive transfer of in vitro induced Treg cells may be a promising therapeutic approach to prevent and treat severe asthma. PMID:22792275

  10. Elevated numbers of SCART1+ gammadelta T cells in skin inflammation and inflammatory bowel disease

    DEFF Research Database (Denmark)

    Fink, Dorte Rosenbek; Holm, Dorte; Schlosser, Anders;

    2010-01-01

    models of human diseases: skin inflammation and inflammatory bowel disease. In the skin inflammation model, an 8.6-fold increase in SCART1(+) cells was observed. Finally, recombinant SCART1 protein was found not to bind to selected bacterial or fungal components or to whole bacteria. Our results show......(+) gammadelta T cells respond to stimulation with bacterial antigens by producing interferon-gamma. The SRCR proteins CD5, CD6, Sp alpha, CD163, and DMBT1/gp-340 are also involved in the immune response, since they are pattern recognition receptors capable of binding directly to bacterial and/or fungal...

  11. Absence of Foxp3+ regulatory T cells during allergen provocation does not exacerbate murine allergic airway inflammation.

    Directory of Open Access Journals (Sweden)

    Abdul Mannan Baru

    Full Text Available Regulatory T cells (Tregs play a non-redundant role in maintenance of immune homeostasis. This is achieved by suppressing both, priming of naïve cells and effector cell functions. Although Tregs have been implicated in modulating allergic immune responses, their influence on distinct phases of development of allergies remains unclear. In this study, by using bacterial artificial chromosome (BAC-transgenic Foxp3-DTR (DEREG mice we demonstrate that the absence of Foxp3(+ Tregs during the allergen challenge surprisingly does not exacerbate allergic airway inflammation in BALB/c mice. As genetic disposition due to strain specificity may contribute significantly to development of allergies, we performed similar experiment in C57BL/6 mice, which are less susceptible to allergy in the model of sensitization used in this study. We report that the genetic background does not influence the consequence of this depletion regimen. These results signify the temporal regulation exerted by Foxp3(+ Tregs in limiting allergic airway inflammation and may influence their application as potential therapeutics.

  12. Interplay between coagulation and vascular inflammation in sickle cell disease

    OpenAIRE

    Sparkenbaugh, Erica; Pawlinski, Rafal

    2013-01-01

    Sickle cell disease is the most common inherited hematologic disorder that leads to the irreversible damage of multiple organs. Although sickling of red blood cells and vaso-occlusion are central to the pathophysiology of sickle cell disease the importance of hemolytic anemia and vasculopathy has been recently recognized. Hypercoagulation state is another prominent feature of sickle cell disease and is mediated by activation of both intrinsic and extrinsic coagulation pathways. Growing eviden...

  13. Human pluripotent stem cell-derived mesenchymal stem cells prevent allergic airway inflammation in mice.

    Science.gov (United States)

    Sun, Yue-Qi; Deng, Meng-Xia; He, Jia; Zeng, Qing-Xiang; Wen, Weiping; Wong, David S H; Tse, Hung-Fat; Xu, Geng; Lian, Qizhou; Shi, Jianbo; Fu, Qing-Ling

    2012-12-01

    We previously found that mesenchymal stem cells (MSCs) derived from human-induced pluripotent stem cells (iPSCs) exerted immunomodulatory effects on Th2-mediated allergic rhinitis in vitro. However, their contribution to the asthma and allergic rhinitis in animal models remains unclear. In this study, we developed a mouse model of ovalbumin (OVA)-induced allergic inflammation in both the upper and lower airways and evaluated the effects of the systemic administration of human iPSC-MSCs and bone marrow-derived MSCs (BM-MSCs) on allergic inflammation. Our results showed that treatments with both the iPSC-MSCs and BM-MSCs before the challenge phase protected the animals from the majority of allergy-specific pathological changes. This protection included an inhibition of inflammatory cell infiltration and mucus production in the lung, a reduction in eosinophil infiltration in the nose, and a decrease in inflammatory cell infiltration in both the bronchoalveolar and nasal lavage fluids. In addition, treatment with iPSC-MSCs or BM-MSCs before the challenge phase resulted in reduced serum levels of Th2 immunoglobulins (e.g., IgE) and decreased levels of Th2 cytokines including interleukin (IL)-4, IL-5, or IL-13 in the bronchoalveolar and/or nasal lavage fluids. Similar therapeutic effects were observed when the animals were pretreated with human iPSC-MSCs before the sensitization phase. These data suggest that iPSC-MSCs may be used as an alternative strategy to adult MSCs in the treatment of asthma and allergic rhinitis. PMID:22987325

  14. Adoptive Transfer of Induced-Treg Cells Effectively Attenuates Murine Airway Allergic Inflammation

    OpenAIRE

    Wei Xu; Qin Lan; Maogen Chen; Hui Chen; Ning Zhu; Xiaohui Zhou; Julie Wang; Huimin Fan; Chun-Song Yan; Jiu-Long Kuang; David Warburton; Dieudonnée Togbe; Bernhard Ryffel; Song-Guo Zheng; Wei Shi

    2012-01-01

    Both nature and induced regulatory T (Treg) lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic...

  15. Extracellular matrix moieties, cytokines, and enzymes: dynamic effects on immune cell behavior and inflammation.

    Science.gov (United States)

    Vaday, G G; Lider, O

    2000-02-01

    Tissue injury caused by infection or physical damage evokes inflammatory reactions and events that are necessary for regaining homeostasis. Central to these events is the translocation of leukocytes, including monocytes, neutrophils, and T lymphocytes, from the vascular system, through endothelium, and into the extracellular matrix (ECM) surrounding the injured tissue. This transition from the vasculature into the site of inflammation elicits remarkable changes in leukocyte behavior as cells adhere to and migrate across ECM before carrying out their effector functions. Growing evidence suggests that, through its interactions with cytokines and degradative enzymes, the ECM microenvironment has a specialized role in providing intrinsic signals for coordinating leukocyte actions. Recent advances also reveal that enzymatic modifications to ECM moieties and cytokines induce distinctive cellular responses, and are likely part of the mechanism regulating the perpetuation or arrest of inflammation. This article reviews the findings that have elucidated the dynamic relationships among these factors and how they communicate with immune cells during inflammation. PMID:10670574

  16. Broncho-Vaxom attenuates allergic airway inflammation by restoring GSK3β-related T regulatory cell insufficiency.

    Directory of Open Access Journals (Sweden)

    Ran Fu

    Full Text Available BACKGROUND: Oral administration of bacterial extracts (eg, Broncho-Vaxom (BV has been proposed to attenuate asthma through modulating Treg cells. However, the underlying mechanism has not been fully characterized. This study sought to assess the effects of oral administration of BV on GSK-3β expression and Treg cells in ovalbumin (OVA-induced asthmatic mice models. METHOD: Asthmatic mice models were established with OVA challenge and treated with oral administration of BV. Next, infiltration of inflammatory cells including eosinophil and neutrophils, mucous metaplasia, levels of Th1/Th2/Treg-typed cytokines and expression of GSK3β and Foxp3 were examined in asthmatic mice models by histological analysis, Bio-Plex and western blot, respectively. Moreover, the frequencies of Treg cells were evaluated in cultured splenocytes by flow cytometry in the presence of BV or GSK3β siRNA interference. RESULTS: We found significant decrease of infiltrated inflammatory cells in bronchoalveolar lavage fluid (BALF in asthmatic mice models after oral administration of BV. Oral administration of BV was shown to significantly suppress mucus metaplasia, Th2-typed cytokine levels and GSK3β expression while increasing Foxp3 production in asthmatic mice models. Moreover, BV significantly enhanced GSK3β-related expansion of Treg cells in cultured spleen cells in vitro. CONCLUSION: Our findings provide evidence that oral administration of BV is capable of attenuating airway inflammation in asthmatic mice models, which may be associated with GSK3β-related expansion of Treg cells.

  17. Donor-derived exosomes induce specific regulatory T cells to suppress immune inflammation in the allograft heart

    OpenAIRE

    Jiangping Song; Jie Huang; Xiao Chen; Xiao Teng; Zhizhao Song; Yong Xing; Mangyuan Wang; Kai Chen; Zheng Wang; Pingchang Yang; Shengshou Hu

    2016-01-01

    To inhibit the immune inflammation in the allografts can be beneficial to organ transplantation. This study aims to induce the donor antigen specific regulatory T cells (Treg cell) inhibit the immune inflammation in the allograft heart. In this study, peripheral exosomes were purified from the mouse serum. A heart transplantation mouse model was developed. The immune inflammation of the allograft heart was assessed by histology and flow cytometry. The results showed that the donor antigen-spe...

  18. Airway epithelial SPDEF integrates goblet cell differentiation and pulmonary Th2 inflammation.

    Science.gov (United States)

    Rajavelu, Priya; Chen, Gang; Xu, Yan; Kitzmiller, Joseph A; Korfhagen, Thomas R; Whitsett, Jeffrey A

    2015-05-01

    Epithelial cells that line the conducting airways provide the initial barrier and innate immune responses to the abundant particles, microbes, and allergens that are inhaled throughout life. The transcription factors SPDEF and FOXA3 are both selectively expressed in epithelial cells lining the conducting airways, where they regulate goblet cell differentiation and mucus production. Moreover, these transcription factors are upregulated in chronic lung disorders, including asthma. Here, we show that expression of SPDEF or FOXA3 in airway epithelial cells in neonatal mice caused goblet cell differentiation, spontaneous eosinophilic inflammation, and airway hyperresponsiveness to methacholine. SPDEF expression promoted DC recruitment and activation in association with induction of Il33, Csf2, thymic stromal lymphopoietin (Tslp), and Ccl20 transcripts. Increased Il4, Il13, Ccl17, and Il25 expression was accompanied by recruitment of Th2 lymphocytes, group 2 innate lymphoid cells, and eosinophils to the lung. SPDEF was required for goblet cell differentiation and pulmonary Th2 inflammation in response to house dust mite (HDM) extract, as both were decreased in neonatal and adult Spdef(-/-) mice compared with control animals. Together, our results indicate that SPDEF causes goblet cell differentiation and Th2 inflammation during postnatal development and is required for goblet cell metaplasia and normal Th2 inflammatory responses to HDM aeroallergen. PMID:25866971

  19. Targeting the thrombin receptor modulates inflammation and astrogliosis to improve recovery after spinal cord injury.

    Science.gov (United States)

    Radulovic, Maja; Yoon, Hyesook; Wu, Jianmin; Mustafa, Karim; Scarisbrick, Isobel A

    2016-09-01

    The deregulation of serine protease activity is a common feature of neurological injury, but little is known regarding their mechanisms of action or whether they can be targeted to facilitate repair. In this study we demonstrate that the thrombin receptor (Protease Activated Receptor 1, (PAR1)) serves as a critical translator of the spinal cord injury (SCI) proteolytic microenvironment into a cascade of pro-inflammatory events that contribute to astrogliosis and functional decline. PAR1 knockout mice displayed improved locomotor recovery after SCI and reduced signatures of inflammation and astrogliosis, including expression of glial fibrillary acidic protein (GFAP), vimentin, and STAT3 signaling. SCI-associated elevations in pro-inflammatory cytokines such as IL-1β and IL-6 were also reduced in PAR1-/- mice and co-ordinate improvements in tissue sparing and preservation of NeuN-positive ventral horn neurons, and PKCγ corticospinal axons, were observed. PAR1 and its agonist's thrombin and neurosin were expressed by perilesional astrocytes and each agonist increased the production of IL-6 and STAT3 signaling in primary astrocyte cultures in a PAR1-dependent manner. In turn, IL-6-stimulated astrocytes increased expression of PAR1, thrombin, and neurosin, pointing to a model in which PAR1 activation contributes to increased astrogliosis by feedforward- and feedback-signaling dynamics. Collectively, these findings identify the thrombin receptor as a key mediator of inflammation and astrogliosis in the aftermath of SCI that can be targeted to reduce neurodegeneration and improve neurobehavioral recovery. PMID:27145117

  20. Interleukin-33: a mediator of inflammation targeting hematopoietic stem and progenitor cells and their progenies

    Directory of Open Access Journals (Sweden)

    Hongnga eLe

    2013-05-01

    Full Text Available Inflammation is defined as a physiological response initiated by a variety of conditions that cause insult to the body, such as infection and tissue injury. Inflammation is triggered by specialized receptors in the innate immune system, which recognized by microbial components known as pathogen-associated molecular patterns (PAMPs or endogenous signals produced by damaged cells (damage-associated molecular patterns, DAMPs. IL-33 is a cytokine that is released predominantly at the epithelial barrier when it is exposed to pathogens, allergens, or injury-inducing stimuli. IL-33 target cells are various, ranging from hematopoietic stem and progenitor cells (HSPCs and essentially all types of their progeny to many nonhematopoietic cells. The pleiotrophic actions of IL-33 suggest that IL-33 is involved in every phase of the inflammatory process. In this review, we discuss recent advances in the understanding of how IL-33 orchestrates inflammatory responses by regulating HSPCs and innate immune cells.

  1. Inflammation and Inflammatory Cells in Myocardial Infarction and Reperfusion Injury: A Double-Edged Sword.

    Science.gov (United States)

    Liu, Jiaqi; Wang, Haijuan; Li, Jun

    2016-01-01

    Myocardial infarction (MI) is the most common cause of cardiac injury, and subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Therefore, inflammation and inflammatory cell infiltration are the hallmarks of MI and reperfusion injury. Ischemic cardiac injury activates the innate immune response via toll-like receptors and upregulates chemokine and cytokine expressions in the infarcted heart. The recruitment of inflammatory cells is a dynamic and superbly orchestrated process. Sequential infiltration of the injured myocardium with neutrophils, monocytes and their descendant macrophages, dendritic cells, and lymphocytes contributes to the initiation and resolution of inflammation, infarct healing, angiogenesis, and ventricular remodeling. Both detrimental effects and a beneficial role in the pathophysiology of MI and reperfusion injury may be attributed to the subset heterogeneity and functional diversity of these inflammatory cells. PMID:27279755

  2. Airway epithelial NF-kappaB activation modulates asbestos-induced inflammation and mucin production in vivo.

    Science.gov (United States)

    Haegens, Astrid; Barrett, Trisha F; Gell, Joanna; Shukla, Arti; Macpherson, Maximilian; Vacek, Pamela; Poynter, Matthew E; Butnor, Kelly J; Janssen-Heininger, Yvonne M; Steele, Chad; Mossman, Brooke T

    2007-02-01

    To investigate the role of bronchiolar epithelial NF-kappaB activity in the development of inflammation and fibrogenesis in a murine model of asbestos inhalation, we used transgenic (Tg) mice expressing an IkappaBalpha mutant (IkappaBalphasr) resistant to phosphorylation-induced degradation and targeted to bronchial epithelium using the CC10 promoter. Sham and chrysotile asbestos-exposed CC10-IkappaBalphasr Tg(+) and Tg(-) mice were examined for altered epithelial cell proliferation and differentiation, cytokine profiles, lung inflammation, and fibrogenesis at 3, 9, and 40 days. KC, IL-6 and IL-1beta were increased (p < or = 0.05) in bronchoalveolar lavage fluid (BALF) from asbestos-exposed mice, but to a lesser extent (p < or = 0.05) in Tg(+) vs Tg(-) mice. Asbestos also caused increases in IL-4, MIP-1beta, and MCP-1 in BALF that were more elevated (p < or = 0.05) in Tg(+) mice at 9 days. Differential cell counts revealed eosinophils in BALF that increased (p < or = 0.05) in Tg(+) mice at 9 days, a time point corresponding with significantly increased numbers of bronchiolar epithelial cells staining positively for mucus production. At all time points, asbestos caused increased numbers of distal bronchiolar epithelial cells and peribronchiolar cells incorporating the proliferation marker, Ki-67. However, bronchiolar epithelial cell and interstitial cell labeling was diminished at 40 days (p < or = 0.05) in Tg(+) vs Tg(-) mice. Our findings demonstrate that airway epithelial NF-kappaB activity plays a role in orchestrating the inflammatory response as well as cell proliferation in response to asbestos.

  3. Dry Needling at Myofascial Trigger Spots of Rabbit Skeletal Muscles Modulates the Biochemicals Associated with Pain, Inflammation, and Hypoxia

    Directory of Open Access Journals (Sweden)

    Yueh-Ling Hsieh

    2012-01-01

    Full Text Available Background and Purpose. Dry needling is an effective therapy for the treatment of pain associated with myofascial trigger point (MTrP. However, the biochemical effects of dry needling that are associated with pain, inflammation, and hypoxia are unclear. This study investigated the activities of β-endorphin, substance P, TNF-α, COX-2, HIF-1α, iNOS, and VEGF after different dosages of dry needling at the myofascial trigger spots (MTrSs of a skeletal muscle in rabbit. Materials and Methods. Dry needling was performed either with one dosage (1D or five dosages (5D into the biceps femoris with MTrSs in New Zealand rabbits. Biceps femoris, serum, and dorsal root ganglion (DRG were sampled immediately and 5 d after dry needling for β-endorphin, substance P, TNF-α, COX-2, HIF-1α, iNOS, and VEGF immunoassays. Results. The 1D treatment enhanced the β-endorphin levels in the biceps femoris and serum and reduced substance P in the biceps femoris and DRG. The 5D treatment reversed these effects and was accompanied by increase of TNF-α, COX-2, HIF-1α, iNOS, and VEGF production in the biceps femoris. Moreover, the higher levels of these biochemicals were still maintained 5 d after treatment. Conclusion. Dry needling at the MTrSs modulates various biochemicals associated with pain, inflammation, and hypoxia in a dose-dependent manner.

  4. Control of Paneth Cell Fate, Intestinal Inflammation, and Tumorigenesis by PKCλ/ι.

    Science.gov (United States)

    Nakanishi, Yuki; Reina-Campos, Miguel; Nakanishi, Naoko; Llado, Victoria; Elmen, Lisa; Peterson, Scott; Campos, Alex; De, Surya K; Leitges, Michael; Ikeuchi, Hiroki; Pellecchia, Maurizio; Blumberg, Richard S; Diaz-Meco, Maria T; Moscat, Jorge

    2016-09-20

    Paneth cells are a highly specialized population of intestinal epithelial cells located in the crypt adjacent to Lgr5(+) stem cells, from which they differentiate through a process that requires downregulation of the Notch pathway. Their ability to store and release antimicrobial peptides protects the host from intestinal pathogens and controls intestinal inflammation. Here, we show that PKCλ/ι is required for Paneth cell differentiation at the level of Atoh1 and Gfi1, through the control of EZH2 stability by direct phosphorylation. The selective inactivation of PKCλ/ι in epithelial cells results in the loss of mature Paneth cells, increased apoptosis and inflammation, and enhanced tumorigenesis. Importantly, PKCλ/ι expression in human Paneth cells decreases with progression of Crohn's disease. Kaplan-Meier survival analysis of colorectal cancer (CRC) patients revealed that low PRKCI levels correlated with significantly worse patient survival rates. Therefore, PKCλ/ι is a negative regulator of intestinal inflammation and cancer through its role in Paneth cell homeostasis. PMID:27653691

  5. Curcuma oil reduces endothelial cell-mediated inflammation in postmyocardial ischemia/reperfusion in rats.

    Science.gov (United States)

    Manhas, Amit; Khanna, Vivek; Prakash, Prem; Goyal, Dipika; Malasoni, Richa; Naqvi, Arshi; Dwivedi, Anil K; Dikshit, Madhu; Jagavelu, Kumaravelu

    2014-09-01

    Endothelial cells initiated inflammation persisting in postmyocardial infarction needs to be controlled and moderated for avoiding fatal complications. Curcuma oil (C.oil, Herbal Medicament), a standardized hexane soluble fraction of Curcuma longa has possessed neuroprotective effect. However, its effect on myocardial ischemia/reperfusion (MI/RP) and endothelial cells remains incompletely defined. Here, using in vivo rat MI/RP injury model and in vitro cellular approaches using EA.hy926 endothelial cells, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and myograph, we provide evidence that with effective regimen and preconditioning of rats with C.oil (250 mg/kg, PO), before and after MI/RP surgery protects rats from MI/RP-induced injury. C.oil treatment reduces left ventricular ischemic area and endothelial cell-induced inflammation, specifically in the ischemic region (*P < 0.0001) and improved endothelial function by reducing the expression of proinflammatory genes and adhesion factors on endothelial cells both in vitro and in vivo. Furthermore, mechanistic studies have revealed that C.oil reduced the expression of adhesion factors like E-selectin (#P = 0.0016) and ICAM-1 ($P = 0.0069) in initiating endothelial cells-induced inflammation. In line to the real-time polymerase chain reaction expression data, C.oil reduced the adhesion of inflammatory cells to endothelial cells as assessed by the interaction of THP-1 monocytes with the endothelial cells using flow-based adhesion and under inflammatory conditions. These studies provide evidence that salutary effect of C.oil on MI/RP could be achieved with pretreatment and posttreatment of rats, C.oil reduced MI/RP-induced injury by reducing the endothelial cell-mediated inflammation, specifically in the ischemic zone of MI/RP rat heart.

  6. Kallikrein transduced mesenchymal stem cells protect against anti-GBM disease and lupus nephritis by ameliorating inflammation and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Yajuan Li

    Full Text Available Previously we have shown that kallikreins (klks play a renoprotective role in nephrotoxic serum induced nephritis. In this study, we have used mesenchymal stem cells (MSCs as vehicles to deliver klks into the injured kidneys and have measured their therapeutic effect on experimental antibody induced nephritis and lupus nephritis. Human KLK-1 (hKLK1 gene was transduced into murine MSCs using a retroviral vector to generate a stable cell line, hKLK1-MSC, expressing high levels of hKLK1. 129/svj mice subjected to anti-GBM induced nephritis were transplanted with 10(6 hKLK1-MSCs and hKLK1 expression was confirmed in the kidneys. Compared with vector-MSCs injected mice, the hKLK1-MSCs treated mice showed significantly reduced proteinuria, blood urea nitrogen (BUN and ameliorated renal pathology. Using the same strategy, we treated lupus-prone B6.Sle1.Sle3 bicongenic mice with hKLK1-MSCs and demonstrated that hKLK1-MSCs delivery also attenuated lupus nephritis. Mechanistically, hKLK1-MSCs reduced macrophage and T-lymphocyte infiltration into the kidney by suppressing the expression of inflammation cytokines. Moreover, hKLK1 transduced MSCs were more resistant to oxidative stress-induced apoptosis. These findings advance genetically modified MSCs as potential gene delivery tools for targeting therapeutic agents to the kidneys in order to modulate inflammation and oxidative stress in lupus nephritis.

  7. The Ameliorative Effect of Sophoricoside on Mast Cell-Mediated Allergic Inflammation in Vivo and in Vitro

    Directory of Open Access Journals (Sweden)

    Jae-Young Um

    2013-05-01

    Full Text Available Sophoricoside exhibits numerous pharmacological effects, including anti- inflammatory and anti-cancer actions, yet the exact mechanism that accounts for the anti-allergic effects of sophoricoside is not completely understood. The aim of the present study was to elucidate whether and how sophoricoside modulates the mast cell-mediated allergic inflammation in vitro and in vivo. We investigated the pharmacological effects of sophoricoside on both compound 48/80 or histamine-induced scratching behaviors and 2,4-dinitrochlorobenzene (DNCB-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of sophoricoside, we evaluated the effects of sophoricoside on the production of histamine and inflammatory cytokines and activation of nuclear factor-κB (NF-κB and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI-stimulated human mast cells (HMC-1. The finding of this study demonstrated that sophoricoside reduced compound 48/80 or histamine-induced scratching behaviors and DNCB-induced atopic dermatitis in mice. Additionally, sophoricoside inhibited the production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of sophoricoside as a potential molecule for use in the treatment of allergic inflammation diseases.

  8. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1.

    NARCIS (Netherlands)

    Pillay, J.; Kamp, V.M.; Hoffen, E. van; Visser, T.; Tak, T.; Lammers, J.W.; Ulfman, L.H.; Leenen, L.P.H.; Pickkers, P.; Koenderman, L.

    2012-01-01

    Suppression of immune responses is necessary to limit damage to host tissue during inflammation, but it can be detrimental in specific immune responses, such as sepsis and antitumor immunity. Recently, immature myeloid cells have been implicated in the suppression of immune responses in mouse models

  9. Activation of factor VII-activating protease in human inflammation: a sensor for cell death

    NARCIS (Netherlands)

    F. Stephan; J.A. Hazelzet; I. Bulder; M.A. Boermeester; J.O. van Till; T. van der Poll; W.A. Wuillemin; L.A. Aarden; S. Zeerleder

    2011-01-01

    Cell death is a central event in the pathogenesis of sepsis and is reflected by circulating nucleosomes. Circulating nucleosomes were suggested to play an important role in inflammation and were demonstrated to correlate with severity and outcome in sepsis patients. We recently showed that plasma ca

  10. Activation of factor VII-activating protease in human inflammation: A sensor for cell death

    NARCIS (Netherlands)

    F. Stephan (Femke); J.A. Hazelzet (Jan); I. Bulder (Ingrid); M.A. Boermeester (Marja); J.W.O. van Till; T. van der Poll (Tom); W.A. Wuillemin (Walter); L.A. Aarden (Lucien); S. Zeerleder (Sacha)

    2011-01-01

    textabstractIntroduction: Cell death is a central event in the pathogenesis of sepsis and is reflected by circulating nucleosomes. Circulating nucleosomes were suggested to play an important role in inflammation and were demonstrated to correlate with severity and outcome in sepsis patients. We rece

  11. Lipopolysaccharide-induced inflammation attenuates taste progenitor cell proliferation and shortens the life span of taste bud cells

    Directory of Open Access Journals (Sweden)

    Brand Joseph

    2010-06-01

    Full Text Available Abstract Background The mammalian taste bud, a complex collection of taste sensory cells, supporting cells, and immature basal cells, is the structural unit for detecting taste stimuli in the oral cavity. Even though the cells of the taste bud undergo constant turnover, the structural homeostasis of the bud is maintained by balancing cell proliferation and cell death. Compared with nongustatory lingual epithelial cells, taste cells express higher levels of several inflammatory receptors and signalling proteins. Whether inflammation, an underlying condition in some diseases associated with taste disorders, interferes with taste cell renewal and turnover is unknown. Here we report the effects of lipopolysaccharide (LPS-induced inflammation on taste progenitor cell proliferation and taste bud cell turnover in mouse taste tissues. Results Intraperitoneal injection of LPS rapidly induced expression of several inflammatory cytokines, including tumor necrosis factor (TNF-α, interferon (IFN-γ, and interleukin (IL-6, in mouse circumvallate and foliate papillae. TNF-α and IFN-γ immunoreactivities were preferentially localized to subsets of cells in taste buds. LPS-induced inflammation significantly reduced the number of 5-bromo-2'-deoxyuridine (BrdU-labeled newborn taste bud cells 1-3 days after LPS injection, suggesting an inhibition of taste bud cell renewal. BrdU pulse-chase experiments showed that BrdU-labeled taste cells had a shorter average life span in LPS-treated mice than in controls. To investigate whether LPS inhibits taste cell renewal by suppressing taste progenitor cell proliferation, we studied the expression of Ki67, a cell proliferation marker. Quantitative real-time RT-PCR revealed that LPS markedly reduced Ki67 mRNA levels in circumvallate and foliate epithelia. Immunofluorescent staining using anti-Ki67 antibodies showed that LPS decreased the number of Ki67-positive cells in the basal regions surrounding circumvallate taste buds

  12. IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer

    DEFF Research Database (Denmark)

    Gyrd-Hansen, Mads; Meier, Pascal

    2010-01-01

    . The development of such inhibitors has radically changed our knowledge of the signalling processes that are regulated by IAPs. Recent studies indicate that IAPs not only regulate caspases and apoptosis, but also modulate inflammatory signalling and immunity, mitogenic kinase signalling, proliferation and mitosis...

  13. Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

    DEFF Research Database (Denmark)

    Romme Christensen, Jeppe; Börnsen, Lars; Ratzer, Rikke;

    2013-01-01

    Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TF...... a pathogenic role of systemic inflammation in progressive MS. These observations may have implications for the treatment of progressive MS.......Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TFH......) cells. Although previous studies reported increased systemic inflammation in progressive MS it remains unclear whether systemic inflammation contributes to disease progression and intrathecal inflammation. This study aimed to investigate systemic inflammation in progressive MS and its relationship...

  14. A Novel Inflammation-Based Stage (I Stage) in Patients with Resectable Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Peng-Cheng Chen; Ji-Feng Feng

    2016-01-01

    Background. Inflammation plays a key role in cancer. In the current study, we proposed a novel inflammation-based stage, named I stage, for patients with resectable esophageal squamous cell carcinoma (ESCC). Methods. Three hundred and twenty-three patients with resectable ESCC were enrolled in the current study. The I stage was calculated as follows: patients with high levels of C-reactive protein (CRP) (>10 mg/L), neutrophil-to-lymphocyte ratio (NLR) (>3.5), and platelet-count-to-lymphocyte ...

  15. Immune modulation by ER stress and inflammation in the tumor microenvironment.

    Science.gov (United States)

    Rodvold, Jeffrey J; Mahadevan, Navin R; Zanetti, Maurizio

    2016-09-28

    It is now increasingly evident that the immune system represents a barrier to tumor emergence, growth, and recurrence. Although this idea was originally proposed almost 50 years ago as the "immune surveillance hypothesis", it is commonly recognized that, with few rare exceptions, tumor cells always prevail. Thus, one of the central unsolved paradoxes of tumor immunology is how a tumor escapes immune control, which is reflected in the lack of effective autochthonous or vaccine-induced anti-tumor T cell responses. In this review, we discuss the role of the endoplasmic reticulum (ER) stress response/unfolded protein response (UPR) in the immunomodulation of myeloid cells and T cells. Specifically, we will discuss how the tumor cell UPR polarizes myeloid cells in a cell-extrinsic manner, and how in turn, thus polarized myeloid cells negatively affect T cell activation and clonal expansion. PMID:26525580

  16. Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress

    Directory of Open Access Journals (Sweden)

    Bibiana Garcia-Bailo

    2011-01-01

    Full Text Available Bibiana Garcia-Bailo1,2, Ahmed El-Sohemy2, Pierre S Haddad3, Paul Arora1,4, Firas BenZaied5, Mohamed Karmali1,2,4, Alaa Badawi11Office for Biotechnology, Genomics and Population Health, Public Health Agency of Canada, Toronto, ON, Canada; 2Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada; 3Natural Health Products and Metabolic Diseases Laboratory, Department of Pharmacology, Université de Montréal and Montreal Diabetes Research Centre, Montreal, QC, Canada; 4Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; 5Canadian College of Naturopathic Medicine, Toronto, ON, CanadaAbstract: The incidence of type 2 diabetes mellitus (T2DM is increasing worldwide, and certain population subgroups are especially vulnerable to the disease. To reduce T2DM risk and progression at the population level, preventative strategies are needed that can be implemented on a population-wide scale with minimal cost and effort. Chronic low-grade inflammation resulting from oxidative stress and imbalances in the innate immune system has been associated with obesity, metabolic syndrome, and insulin resistance – critical stages in the development and progression of T2DM. Therefore, inflammation may play a causal role in the pathogenesis of T2DM, and reducing it via modulation of oxidative stress and the innate immune response could lead to a status of improved insulin sensitivity and delayed disease onset. Dietary supplementation with anti-inflammatory and antioxidant nutritional factors, such as micronutrients, might present a novel strategy toward the prevention and control of T2DM at the population level. This review examines current knowledge linking oxidation, inflammatory signaling pathways, and vitamin supplementation or intake to the risk of T2DM. The concept that micronutrients, via attenuation of inflammation, could be employed as a novel preventive measure for T2DM is evaluated in the context of its

  17. Bystander suppression of allergic airway inflammation by lung resident memory CD8+ T cells

    Science.gov (United States)

    Marsland, Benjamin J.; Harris, Nicola L.; Camberis, Mali; Kopf, Manfred; Hook, Sarah M.; Le Gros, Graham

    2004-04-01

    CD8+ memory T cells have recently been recognized as playing a key role in natural immunity against unrelated viral infections, a phenomenon referred to as "heterologous antiviral immunity." We now provide data that the cellular immunological interactions that underlie such heterologous immunity can play an equally important role in regulating T helper 2 immune responses and protecting mucosal surfaces from allergen-induced inflammation. Our data show that CD8+ T cells, either retained in the lung after infection with influenza virus, or adoptively transferred via the intranasal route can suppress allergic airway inflammation. The suppression is mediated by IFN-, which acts to reduce the activation level, T helper 2 cytokine production, airways hyperresponsiveness, and migration of allergen-specific CD4+ T cells into the lung, whereas the systemic and draining lymph node responses remain unchanged. Of note, adoptive transfer of previously activated transgenic CD8+ T cells conferred protection against allergic airway inflammation, even in the absence of specific-antigen. Airway resident CD8+ T cells produced IFN- when directly exposed to conditioned media from activated dendritic cells or the proinflammatory cytokines IL-12 and IL-18. Taken together these data indicate that effector/memory CD8+ T cells present in the airways produce IFN- after inflammatory stimuli, independent of specific-antigen, and as a consequence play a key role in modifying the degree and frequency of allergic responses in the lung.

  18. Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells

    Science.gov (United States)

    Barbosa, João P; Neves, Ana R; Silva, Andreia M; Barbosa, Mário A; Reis, M Salette; Santos, Susana G

    2016-01-01

    Dendritic cells (DCs) are promising targets for drug delivery, as they can induce immunity or tolerance. The current study aims to examine the potential of using nanostructured lipid carriers (NLC) as delivery systems for human DC by evaluating nanoparticle internalization, cell labeling, and drug activity. NLC were formulated incorporating the fluorochrome fluorescein isothiocyanate (FITC-NLC) or the natural anti-inflammatory molecule resveratrol (rsv-NLC). Primary human DCs were differentiated from peripheral blood monocytes, and the innovative imaging flow cytometry technique was used to examine FITC-NLC internalization. The capacity of rsv-NLC to inhibit DC activation in response to proinflammatory cytokine tumor necrosis factor-α (TNF- α) was investigated by conventional flow cytometry. A combination of imaging and conventional flow cytometry was used to assess NLC cytotoxicity. The results obtained indicate that both NLC formulations were stable over time, with mean diameter nuclear factor κ beta phosphorylation and significantly decrease the level of interleukin-12/23, both upregulated in response to TNF-α, while 10 µM free rsv were needed to promote a similar effect. Taken together, the results presented show that NLC are suitable carriers of fluorescent labels or bioactive molecules for human DCs, leading to inflammation modulation.

  19. IL-22 is produced by innate lymphoid cells and limits inflammation in allergic airway disease.

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    Christian Taube

    Full Text Available Interleukin (IL-22 is an effector cytokine, which acts primarily on epithelial cells in the skin, gut, liver and lung. Both pro- and anti-inflammatory properties have been reported for IL-22 depending on the tissue and disease model. In a murine model of allergic airway inflammation, we found that IL-22 is predominantly produced by innate lymphoid cells in the inflamed lungs, rather than TH cells. To determine the impact of IL-22 on airway inflammation, we used allergen-sensitized IL-22-deficient mice and found that they suffer from significantly higher airway hyperreactivity upon airway challenge. IL-22-deficiency led to increased eosinophil infiltration lymphocyte invasion and production of CCL17 (TARC, IL-5 and IL-13 in the lung. Mice treated with IL-22 before antigen challenge displayed reduced expression of CCL17 and IL-13 and significant amelioration of airway constriction and inflammation. We conclude that innate IL-22 limits airway inflammation, tissue damage and clinical decline in allergic lung disease.

  20. Capsaicinoids Cause Inflammation and Epithelial Cell Death through Activation of Vanilloid Receptors

    OpenAIRE

    Reilly, Christopher A.; Taylor, Jack L.; Lanza, Diane L.; Carr, Brian A.; Crouch, Dennis J.; Yost, Garold S.

    2003-01-01

    Capsaicinoids, found in less-than-lethal self-defense weapons, have been associated with respiratory failure and death in exposed animals and people. The studies described herein provide evidence for acute respiratory inflammation and damage to epithelial cells in experimental animals, and provide precise molecular mechanisms that mediate these effects using human bronchiolar and alveolar epithelial cells. Inhalation exposure of rats to pepper sprays (capsaicinoids) produced acute inflammatio...

  1. Innate lymphoid cells in the initiation, regulation and resolution of inflammation

    OpenAIRE

    Sonnenberg, Gregory F.; Artis, David

    2015-01-01

    A previously unappreciated cell type of the innate immune system, termed innate lymphoid cells (ILCs), has been characterized in mice and humans, and found to profoundly influence the induction, regulation and resolution of inflammation. ILCs play an important role in these processes in murine models of infection, inflammatory disease and tissue repair. Further, disease association studies in defined patient populations have identified significant alterations in ILC responses, suggesting a po...

  2. Innate Lymphoid Cells: Balancing Immunity, Inflammation, and Tissue Repair in the Intestine

    OpenAIRE

    Wojno, Elia D. Tait; Artis, David

    2012-01-01

    Innate lymphoid cells (ILCs) are a recently described group of innate immune cells that can regulate immunity, inflammation, and tissue repair in multiple anatomical compartments, particularly the barrier surfaces of the skin, airways, and intestine. Broad categories of ILCs have been defined based on transcription factor expression and the ability to produce distinct patterns of effector molecules. Recent studies have revealed that ILC populations can regulate commensal bacterial communities...

  3. Suppression of allergic airway inflammation in a mouse model of asthma by exogenous mesenchymal stem cells.

    Science.gov (United States)

    Ou-Yang, Hai-Feng; Huang, Yun; Hu, Xing-Bin; Wu, Chang-Gui

    2011-12-01

    Mesenchymal stem cells (MSCs) have significant immunomodulatory effects in the development of acute lung inflammation and fibrosis. However, it is still unclear as to whether MSCs could attenuate allergic airway inflammation in a mouse model of asthma. We firstly investigated whether exogenous MSCs can relocate to lung tissues in asthmatic mice and analyzed the chemotactic mechanism. Then, we evaluated the in vivo immunomodulatory effect of exogenous MSCs in asthma. MSCs (2 × 10(6)) were administered through the tail vein to mice one day before the first airway challenge. Migration of MSCs was evaluated by flow cytometry. The immunomodulatory effect of MSCs was evaluated by cell counting in bronchoalveolar lavage fluid (BALF), histology, mast cell degranulation, airway hyperreactivity and cytokine profile in BALF. Exogenous MSCs can migrate to sites of inflammation in asthmatic mice through a stromal cell-derived factor-1α/CXCR4-dependent mechanism. MSCs can protect mice against a range of allergic airway inflammatory pathologies, including the infiltration of inflammatory cells, mast cell degranulation and airway hyperreactivity partly via shifting to a T-helper 1 (Th1) from a Th2 immune response to allergens. So, immunotherapy based on MSCs may be a feasible, efficient therapy for asthma. PMID:22114062

  4. Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan; Zhao, Yue; Xu, Wenchao; Luo, Fei; Wang, Bairu; Li, Yuan; Pang, Ying; Liu, Qizhan, E-mail: drqzliu@hotmail.com

    2013-10-15

    Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study, we investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. The results showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β). The data also indicated that HIF-2α was involved in arsenite-induced inflammation. Moreover, IL-6 and IL-8 were essential for the malignant progression of arsenite-transformed HBE cells. Thus, these experiments show that HIF-2α mediates arsenite-induced inflammation and that such inflammation is involved in arsenite-induced malignant transformation of HBE cells. The results provide a link between the inflammatory response and the acquisition of a malignant transformed phenotype by cells chronically exposed to arsenite and thus establish a previously unknown mechanism for arsenite-induced carcinogenesis. - Highlights: • Arsenite induces inflammation. • Arsenite-induced the increases of IL-6 and IL-8 via HIF-2α. • Inflammation is involved in arsenite-induced carcinogenesis.

  5. Invariant Natural Killer T (iNKT Cells Prevent Autoimmunity, but Induce Pulmonary Inflammation in Cystic Fibrosis

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    Nanna Siegmann

    2014-06-01

    Full Text Available Background/Aims: Inflammation is a major and critical component of the lung pathology in the hereditary disease cystic fibrosis. The molecular mechanisms of chronic inflammation in cystic fibrosis require definition. Methods: We used several genetic mouse models to test a role of iNKT cells and ceramide in pulmonary inflammation of cystic fibrosis mice. Inflammation was determined by the pulmonary cytokine profil and the abundance of inflammatory cells in the lung. Results: Here we provide a new concept how inflammation in the lung of individuals with cystic fibrosis is initiated. We show that in cystic fibrosis mice the mutation in the Cftr gene provokes a significant up-regulation of iNKT cells in the lung. Accumulation of iNKT cells serves to control autoimmune disease, which is triggered by a ceramide-mediated induction of cell death in CF organs. Autoimmunity becomes in particular overt in cystic fibrosis mice lacking iNKT cells and although suppression of the autoimmune response by iNKT cells is beneficial, IL-17+ iNKT cells attract macrophages and neutrophils to CF lungs resulting in chronic inflammation. Genetic deletion of iNKT cells in cystic fibrosis mice prevents inflammation in CF lungs. Conclusion: Our data demonstrate an important function of iNKT cells in the chronic inflammation affecting cystic fibrosis lungs. iNKT cells suppress the auto-immune response induced by ceramide-mediated death of epithelial cells in CF lungs, but also induce a chronic pulmonary inflammation.

  6. Deletion of Foxp3+ regulatory T cells in genetically targeted mice supports development of intestinal inflammation

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    Boehm Franziska

    2012-07-01

    Full Text Available Abstract Background Mice lacking Foxp3+ regulatory T (Treg cells develop severe tissue inflammation in lung, skin, and liver with premature death, whereas the intestine remains uninflamed. This study aims to demonstrate the importance of Foxp3+ Treg for the activation of T cells and the development of intestinal inflammation. Methods Foxp3-GFP-DTR (human diphtheria toxin receptor C57BL/6 mice allow elimination of Foxp3+ Treg by treatment with Dx (diphtheria toxin. The influence of Foxp3+ Treg on intestinal inflammation was tested using the CD4+ T-cell transfer colitis model in Rag−/− C57BL/6 mice and the acute DSS-colitis model. Results Continuous depletion of Foxp3+ Treg in Foxp3-GFP-DTR mice led to dramatic weight loss and death of mice by day 28. After 10 days of depletion of Foxp3+ Treg, isolated CD4+ T-cells were activated and produced extensive amounts of IFN-γ, IL-13, and IL-17A. Transfer of total CD4+ T-cells isolated from Foxp3-GFP-DTR mice did not result in any changes of intestinal homeostasis in Rag−/− C57BL/6 mice. However, administration of DTx between days 14 and 18 after T-cell reconstitution, lead to elimination of Foxp3+ Treg and to immediate weight loss due to intestinal inflammation. This pro-inflammatory effect of Foxp3+ Treg depletion consecutively increased inflammatory cytokine production. Further, the depletion of Foxp3+ Treg from Foxp3-GFP-DTR mice increased the severity of acute dSS-colitis accompanied by 80% lethality of Treg-depleted mice. CD4+ effector T-cells from Foxp3+ Treg-depleted mice produced significantly more pro-inflammatory cytokines. Conclusion Intermittent depletion of Foxp3+ Treg aggravates intestinal inflammatory responses demonstrating the importance of Foxp3+ Treg for the balance at the mucosal surface of the intestine.

  7. Profile of Inflammation-associated genes during Hepatic Differentiation of Human Pluripotent Stem Cells.

    Science.gov (United States)

    Ignatius Irudayam, Joseph; Contreras, Deisy; Spurka, Lindsay; Ren, Songyang; Kanagavel, Vidhya; Ramaiah, Arunachalam; Annamalai, Alagappan; French, Samuel W; Klein, Andrew S; Funari, Vincent; Arumugaswami, Vaithilingaraja

    2015-12-01

    Expression of genes associated with inflammation was analyzed during differentiation of human pluripotent stem cells (PSCs) to hepatic cells. Messenger RNA transcript profiles of differentiated endoderm (day 5), hepatoblast (day 15) and hepatocyte-like cells (day 21) were obtained by RNA sequencing analysis. When compared to endoderm cells an immature cell type, the hepatic cells (days 15 and 21) had significantly higher expression of acute phase protein genes including complement factors, coagulation factors, serum amyloid A and serpins. Furthermore, hepatic phase of cells expressed proinflammatory cytokines IL18 and IL32 as well as cytokine receptors IL18R1, IL1R1, IL1RAP, IL2RG, IL6R, IL6ST and IL10RB. These cells also produced CCL14, CCL15, and CXCL- 1, 2, 3, 16 and 17 chemokines. Endoderm cells had higher levels of chemokine receptors, CXCR4 and CXCR7, than that of hepatic cells. Sirtuin family of genes involved in aging, inflammation and metabolism were differentially regulated in endoderm and hepatic phase cells. Ligands and receptors of the tumor necrosis factor (TNF) family as well as downstream signaling factors TRAF2, TRAF4, FADD, NFKB1 and NFKBIB were differentially expressed during hepatic differentiation. PMID:26702414

  8. Role of Hematopoietic Stem Cells in Inflammation of the Pancreas during Diabetes Mellitus.

    Science.gov (United States)

    Dygai, A M; Skurikhin, E G; Pershina, O V; Ermakova, N N; Krupin, V A; Ermolaeva, L A; Stakheeva, M N; Choinzonov, E L; Goldberg, V E; Reikhart, D V; Ellinidi, V N; Kravtsov, V Yu

    2016-02-01

    The model of streptozotocin-induced diabetes mellitus in C57Bl/6 mice was employed to study the role of precursors of insulin-producing β-cells, hematopoietic stem cells, and progenitor hematopoietic cells in inflammation. In addition to provoking hyperglycemia, streptozotocin elevated serum levels of IL-1β and hyaluronic acid, induced edema in the pancreatic insular tissue and its infiltration by inflammatory cells (neutrophils, lymphocytes, and macrophages) and fibroblasts. Inflammation in pancreatic islets was accompanied by necrotic processes and decreasing counts of multipotent progenitor β-cells (CD45(-), TER119(-), c-kit-1(-), and Flk-1(-)), oligopotent progenitor β-cells (CD45(-), TER119(-), CD133(+), and CD49f(low)), and insulinproducing β-cells (Pdx1(+)). Pancreatic infl ammation was preceded by elevation of the number of short-term hematopoietic stem cells (Lin-Sca-1(+)c-kit(+)CD34(+)) relative to long-term cells (Lin(-)Sca-1(+)c-kit(+)CD34(-)) in the bone marrow as well as recruitment of hematopoietic stem and progenitor cells into circulation. Transplantation of bone marrow hematopoietic stem and progenitor cells from diabetic C57Bl/6 donor mice to recipient CBA mice with 5-fluorouracilinduced leukopenia accelerated regeneration of granulocytopoiesis in recipient mice. PMID:26906195

  9. Profile of Inflammation-associated genes during Hepatic Differentiation of Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Joseph Ignatius Irudayam

    2015-12-01

    Full Text Available Expression of genes associated with inflammation was analyzed during differentiation of human pluripotent stem cells (PSCs to hepatic cells. Messenger RNA transcript profiles of differentiated endoderm (day 5, hepatoblast (day 15 and hepatocyte-like cells (day 21 were obtained by RNA sequencing analysis. When compared to endoderm cells an immature cell type, the hepatic cells (days 15 and 21 had significantly higher expression of acute phase protein genes including complement factors, coagulation factors, serum amyloid A and serpins. Furthermore, hepatic phase of cells expressed proinflammatory cytokines IL18 and IL32 as well as cytokine receptors IL18R1, IL1R1, IL1RAP, IL2RG, IL6R, IL6ST and IL10RB. These cells also produced CCL14, CCL15, and CXCL- 1, 2, 3, 16 and 17 chemokines. Endoderm cells had higher levels of chemokine receptors, CXCR4 and CXCR7, than that of hepatic cells. Sirtuin family of genes involved in aging, inflammation and metabolism were differentially regulated in endoderm and hepatic phase cells. Ligands and receptors of the tumor necrosis factor (TNF family as well as downstream signaling factors TRAF2, TRAF4, FADD, NFKB1 and NFKBIB were differentially expressed during hepatic differentiation.

  10. Scavenger Receptor CD36 Expression Contributes to Adipose Tissue Inflammation and Cell Death in Diet-Induced Obesity

    OpenAIRE

    Lei Cai; Zhen Wang; Ailing Ji; Meyer, Jason M.; Deneys R. van der Westhuyzen

    2012-01-01

    OBJECTIVE: The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death. EXPERIMENTAL APPROACH: Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT) mice fed a high fat diet (60% kcal fat) fo...

  11. Modulation of inflammation by vitamin E and C supplementation prior to anterior cruciate ligament surgery.

    Science.gov (United States)

    Barker, Tyler; Leonard, Scott W; Trawick, Roy H; Martins, Thomas B; Kjeldsberg, Carl R; Hill, Harry R; Traber, Maret G

    2009-03-01

    Muscle atrophy commonly follows anterior cruciate ligament (ACL) injury and surgery. Proinflammatory cytokines can induce and exacerbate oxidative stress, potentiating muscle atrophy. The purpose of this study was to evaluate the influence of prior antioxidant (AO) supplementation on circulating cytokines following ACL surgery. A randomized, double-blind, placebo-controlled trial was conducted in men undergoing ACL surgery, who were randomly assigned to either: (1) AO (200 IU of vitamin E (50% d-alpha-tocopheryl acetate and 50% d-alpha-tocopherol) and 500 mg ascorbic acid), or (2) matching placebos (PL). Subjects took supplements twice daily for 2 weeks prior to and up to 12 weeks after surgery. Each subject provided five blood samples: (1) baseline (Bsl, prior to supplementation and approximately 2 weeks prior to surgery), (2) presurgery (Pre), (3) 90 min, (4) 72 h, and (5) 7 days postsurgery. Following surgery, inflammation and muscle damage increased in both groups, as assessed by increased circulating IL-6, C-reactive protein, and creatine kinase. During AO supplementation, plasma alpha-T and AA increased while gamma-T concentrations decreased significantly (PACL surgery.

  12. Protective effects of surfactant protein D treatment in 1,3-β-glucan-modulated allergic inflammation.

    Science.gov (United States)

    Fakih, Dalia; Pilecki, Bartosz; Schlosser, Anders; Jepsen, Christine S; Thomsen, Laura K; Ormhøj, Maria; Watson, Alastair; Madsen, Jens; Clark, Howard W; Barfod, Kenneth K; Hansen, Soren; Marcussen, Niels; Jounblat, Rania; Chamat, Soulaima; Holmskov, Uffe; Sorensen, Grith L

    2015-12-01

    Surfactant protein D (SP-D) is a pulmonary collectin important in lung immunity. SP-D-deficient mice (Sftpd(-/-)) are reported to be susceptible to ovalbumin (OVA)- and fungal allergen-induced pulmonary inflammation, while treatment with exogenous SP-D has therapeutic effects in such disease models. β-Glucans are a diverse group of polysaccharides previously suggested to serve as fungal ligands for SP-D. We set out to investigate if SP-D could interact with 1,3-β-glucan and attenuate allergic pulmonary inflammation in the presence of 1,3-β-glucan. Allergic airway disease was induced in Sftpd(-/-) and Sftpd(+/+) mice by OVA sensitization and subsequent challenge with OVA, 1,3-β-glucan, or OVA/1,3-β-glucan together. Mice in the combined treatment group were further treated with a high dose of recombinant fragment of human SP-D (rfhSP-D). We demonstrated direct interaction between SP-D and 1,3-β-glucan. OVA-induced mucous cell metaplasia was increased in Sftpd(-/-) mice, supporting previously reported protective effects of endogenous SP-D in allergy. OVA-induced parenchymal CCL11 levels and eosinophilic infiltration in bronchoalveolar lavage were unaffected by 1,3-β-glucan, but were reversed with rfhSP-D treatment. 1,3-β-Glucan treatment did, however, induce pulmonary neutrophilic infiltration and increased TNF-α levels in bronchoalveolar lavage, independently of OVA-induced allergy. This infiltration was also reversed by treatment with rfhSP-D. 1,3-β-Glucan reduced OVA-induced mucous cell metaplasia, T helper 2 cytokines, and IFN-γ production. rfhSP-D treatment further reduced mucous metaplasia and T helper 2 cytokine secretion to background levels. In summary, rfhSP-D treatment resulted in attenuation of both allergic inflammation and 1,3-β-glucan-mediated neutrophilic inflammation. Our data suggest that treatment with high-dose SP-D protects from mold-induced exacerbations of allergic asthma.

  13. Wound Healing and Cancer Stem Cells: Inflammation as a Driver of Treatment Resistance in Breast Cancer

    Science.gov (United States)

    Arnold, Kimberly M; Opdenaker, Lynn M; Flynn, Daniel; Sims-Mourtada, Jennifer

    2015-01-01

    The relationship between wound healing and cancer has long been recognized. The mechanisms that regulate wound healing have been shown to promote transformation and growth of malignant cells. In addition, chronic inflammation has been associated with malignant transformation in many tissues. Recently, pathways involved in inflammation and wound healing have been reported to enhance cancer stem cell (CSC) populations. These cells, which are highly resistant to current treatments, are capable of repopulating the tumor after treatment, causing local and systemic recurrences. In this review, we highlight proinflammatory cytokines and developmental pathways involved in tissue repair, whose deregulation in the tumor microenvironment may promote growth and survival of CSCs. We propose that the addition of anti-inflammatory agents to current treatment regimens may slow the growth of CSCs and improve therapeutic outcomes. PMID:25674014

  14. Distinct Tlr4-expressing cell compartments control neutrophilic and eosinophilic airway inflammation.

    Science.gov (United States)

    McAlees, J W; Whitehead, G S; Harley, I T W; Cappelletti, M; Rewerts, C L; Holdcroft, A M; Divanovic, S; Wills-Karp, M; Finkelman, F D; Karp, C L; Cook, D N

    2015-07-01

    Allergic asthma is a chronic, inflammatory lung disease. Some forms of allergic asthma are characterized by T helper type 2 (Th2)-driven eosinophilia, whereas others are distinguished by Th17-driven neutrophilia. Stimulation of Toll-like receptor 4 (TLR4) on hematopoietic and airway epithelial cells (AECs) contributes to the inflammatory response to lipopolysaccharide (LPS) and allergens, but the specific contribution of TLR4 in these cell compartments to airway inflammatory responses remains poorly understood. We used novel, conditionally mutant Tlr4(fl/fl) mice to define the relative contributions of AEC and hematopoietic cell Tlr4 expression to LPS- and allergen-induced airway inflammation. We found that Tlr4 expression by hematopoietic cells is critical for neutrophilic airway inflammation following LPS exposure and for Th17-driven neutrophilic responses to the house dust mite (HDM) lysates and ovalbumin (OVA). Conversely, Tlr4 expression by AECs was found to be important for robust eosinophilic airway inflammation following sensitization and challenge with these same allergens. Thus, Tlr4 expression by hematopoietic and airway epithelial cells controls distinct arms of the immune response to inhaled allergens. PMID:25465099

  15. Effect of mesenchymal stem cells on inhibiting airway remodeling and airway inflammation in chronic asthma.

    Science.gov (United States)

    Ge, Xiahui; Bai, Chong; Yang, Jianming; Lou, Guoliang; Li, Qiang; Chen, Ruohua

    2013-07-01

    Previous studies proved that bone marrow-derived mesenchymal stem cells (BMSCs) could improve a variety of immune-mediated disease by its immunomodulatory properties. In this study, we investigated the effect on airway remodeling and airway inflammation by administrating BMSCs in chronic asthmatic mice. Forty-eight female BALB/c mice were randomly distributed into PBS group, BMSCs treatment group, BMSCs control group, and asthmatic group. The levels of cytokine and immunoglobulin in serum and bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay. The number of CD4(+) CD25(+) regulatory T cells and morphometric analysis was determined by flow cytometry, hematoxylin-eosin, immunofluorescence staining, periodic-acid Schiff, and masson staining, respectively. We found that airway remodeling and airway inflammation were evident in asthmatic mice. Moreover, low level of IL-12 and high levels of IL-13, IL-4, OVA-specific IgG1, IgE, and IgG2a and the fewer number of CD4(+) CD25(+) regulatory T cells were present in asthmatic group. However, transplantation of BMSCs significantly decreased airway inflammation and airway remodeling and level of IL-4, OVA-specific IgE, and OVA-specific IgG1, but elevated level of IL-12 and the number of CD4 + CD25 + regulatory T cells in asthma (P cells in asthma, but not contribution to lung regeneration. PMID:23334934

  16. Local Microenvironment Controls the Compartmentalization of NK Cell Responses during Systemic Inflammation in Mice.

    Science.gov (United States)

    Rasid, Orhan; Ciulean, Ioana Sonya; Fitting, Catherine; Doyen, Noelle; Cavaillon, Jean-Marc

    2016-09-15

    Systemic inflammatory response syndrome is a whole-body reaction to a triggering insult that often results in life-threatening illness. Contributing to the development of this inflammatory cascade are numerous cellular partners, among which NK cells were shown to play a key role. Accumulating evidence points to organ-specific properties of systemic inflammation and NK cells. However, little is known about compartment-specific activation of NK cells during systemic inflammatory response syndrome or the relative contribution of NK cell-intrinsic properties and microenvironmental cues. In this study, we undertook a sequential characterization of NK responses in the spleen, lungs, bone marrow, peritoneum, and blood using a mouse model of endotoxemia. We report that, despite similar systemic dynamics of NK cell responses, expression of activation markers (CD69 and CD25) and effector molecules (IFN-γ, granzyme B, and IL-10) display organ-specific thresholds of maximum activation. Using adoptive transfers of spleen and lung NK cells, we found that these cells have the capacity to quickly adapt to a new environment and adjust their response levels to that of resident NK cells. This functional adaptation occurs without significant alterations in phenotype and independently of subpopulation-specific trafficking. Thus, using a dynamic in vivo-transfer system, to our knowledge our study is the first to report the compartmentalization of NK cells responses during systemic inflammation and to show that NK cell-intrinsic properties and microenvironmental cues are involved in this process, in a sequential manner. PMID:27521338

  17. Natural Killer p46 Controls Hepatitis B Virus Replication and Modulates Liver Inflammation.

    Directory of Open Access Journals (Sweden)

    Wanyu Li

    Full Text Available Natural killer (NK cells play an important role in hepatitis B virus (HBV infection control, and are regulated by a complex network of activating and inhibitory receptors. However, NK cell activity in HBV patients remains poorly understood. The objective of this study was to investigate the phenotypic and functional characteristics of circulating NK cells in patients during different chronic hepatitis B (CHB infection stages. We investigated NK cell phenotypes, receptor expression and function in 86 CHB patients and 20 healthy controls. NK cells were purified and NK cell subsets were characterized by flow cytometry. Cytotoxic activity (CD107a and interferon-gamma (IFN-γ secretion were examined, and Natural Killer p46 (NKP46 blockade and spontaneous NK cell cytolytic activity against K562, HepG2 and HepG2.215 cell lines was studied. Activating NKp46 receptor expression was higher in inactive HBsAg carriers when compared with other groups (p = 0.008. NKp46 expression negatively correlated with HBV DNA (R = -0.253, p = 0.049 and ALT (R = -0.256, p = 0.045 levels. CD107a was higher in immune-activated groups when compared with immune-tolerant groups (p = 0.039. CD107a expression was related to viral load (p = 0.02 and HBeAg status (p = 0.024. In vitro NKp46 blockade reduced NK cell cytolytic activity against HepG2 and HepG2.215 cell lines (p = 0.02; p = 0.039. Furthermore, NK cells from high viral load CHB patients displayed significantly lower specific cytolytic activity against anti-NKp46-loaded K562 targets (p = 0.0321. No significant differences were observed in IFN-γ secretion (p > 0.05. In conclusion, NKp46 expression regulates NK cell cytolytic function. NKp46 may moderate NK cell activity during HBV replication suppression and HBV-associated liver damage and may be critical for NK cell activity during CHB infection.

  18. A Quantitative Analysis of Photovoltaic Modules Using Halved Cells

    Directory of Open Access Journals (Sweden)

    S. Guo

    2013-01-01

    Full Text Available In a silicon wafer-based photovoltaic (PV module, significant power is lost due to current transport through the ribbons interconnecting neighbour cells. Using halved cells in PV modules is an effective method to reduce the resistive power loss which has already been applied by some major PV manufacturers (Mitsubishi, BP Solar in their commercial available PV modules. As a consequence, quantitative analysis of PV modules using halved cells is needed. In this paper we investigate theoretically and experimentally the difference between modules made with halved and full-size solar cells. Theoretically, we find an improvement in fill factor of 1.8% absolute and output power of 90 mW for the halved cell minimodule. Experimentally, we find an improvement in fill factor of 1.3% absolute and output power of 60 mW for the halved cell module. Also, we investigate theoretically how this effect confers to the case of large-size modules. It is found that the performance increment of halved cell PV modules is even higher for high-efficiency solar cells. After that, the resistive loss of large-size modules with different interconnection schemes is analysed. Finally, factors influencing the performance and cost of industrial halved cell PV modules are discussed.

  19. Knockdown of GRP78 promotes apoptosis in pancreatic acinar cells and attenuates the severity of cerulein and LPS induced pancreatic inflammation.

    Directory of Open Access Journals (Sweden)

    Yong Liu

    Full Text Available Acute pancreatitis (AP is a potentially lethal disease characterized by inflammation and parenchymal cell death; also, the severity of AP correlates directly with necrosis and inversely with apoptosis. However, mechanisms of regulating cell death in AP remain unclear. The endoplasmic reticulum (ER chaperone protein GRP78 has anti-apoptotic properties, in addition to modulating ER stress responses. This study used RNA interference (RNAi approach to investigate the potential role of GRP78 in regulating apoptosis during AP. In vitro models of AP were successfully developed by treating AR42J cells with cerulein or cerulein plus lipoplysaccharide (LPS. There was more pancreatic inflammation and less apoptosis with the cerulein plus LPS treatment. Furthermore, knockdown of GRP78 expression markedly promoted apoptosis and reduced necrosis in pancreatic acinar cells. This was accomplished by enhancing the activation of caspases and inhibiting the activity of X-linked inhibitor of apoptosis protein (XIAP, as well as a receptor interacting protein kinase-1(RIPK1, which is a key mediator of necrosis. This attenuated the severity of pancreatic inflammation, especially after cerulein plus LPS treatment. In conclusion, these findings indicate that GRP78 plays an anti-apoptotic role in regulating the cell death response during AP. Therefore, GRP78 is a potential therapeutic target for AP.

  20. Tomato Aqueous Extract Modulates the Inflammatory Profile of Immune Cells and Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Joseph Schwager

    2016-01-01

    Full Text Available Nutrients transiently or chronically modulate functional and biochemical characteristics of cells and tissues both in vivo and in vitro. The influence of tomato aqueous extract (TAE on the in vitro inflammatory response of activated human peripheral blood leukocytes (PBLs and macrophages was investigated. Its effect on endothelial dysfunction (ED was analyzed in human umbilical vein endothelial cells (HUVECs. Murine macrophages (RAW264.7 cells, PBLs and HUVECs were incubated with TAE. They were activated with LPS or TNF-α in order to induce inflammatory processes and ED, respectively. Inflammatory mediators and adhesion molecules were measured by immune assay-based multiplex analysis. Gene expression was quantified by RT-PCR. TAE altered the production of interleukins (IL-1β, IL-6, IL-10, IL-12 and chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, CXCL8/IL-8, CXCL10/IP-10 in PBLs. TAE reduced ED-associated expression of adhesion molecules (ICAM-1, VCAM-1 in endothelial cell. In macrophages, the production of nitric oxide, PGE2, cytokines and ILs (TNF-α, IL-1β, IL-6, IL-12, which reflects chronic inflammatory processes, was reduced. Adenosine was identified as the main bioactive of TAE. Thus, TAE had cell-specific and context-dependent effects. We infer from these in vitro data, that during acute inflammation TAE enhances cellular alertness and therefore the sensing of disturbed immune homeostasis in the vascular-endothelial compartment. Conversely, it blunts inflammatory mediators in macrophages during chronic inflammation. A novel concept of immune regulation by this extract is proposed.

  1. Tomato Aqueous Extract Modulates the Inflammatory Profile of Immune Cells and Endothelial Cells.

    Science.gov (United States)

    Schwager, Joseph; Richard, Nathalie; Mussler, Bernd; Raederstorff, Daniel

    2016-01-01

    Nutrients transiently or chronically modulate functional and biochemical characteristics of cells and tissues both in vivo and in vitro. The influence of tomato aqueous extract (TAE) on the in vitro inflammatory response of activated human peripheral blood leukocytes (PBLs) and macrophages was investigated. Its effect on endothelial dysfunction (ED) was analyzed in human umbilical vein endothelial cells (HUVECs). Murine macrophages (RAW264.7 cells), PBLs and HUVECs were incubated with TAE. They were activated with LPS or TNF-α in order to induce inflammatory processes and ED, respectively. Inflammatory mediators and adhesion molecules were measured by immune assay-based multiplex analysis. Gene expression was quantified by RT-PCR. TAE altered the production of interleukins (IL-1β, IL-6, IL-10, IL-12) and chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, CXCL8/IL-8, CXCL10/IP-10) in PBLs. TAE reduced ED-associated expression of adhesion molecules (ICAM-1, VCAM-1) in endothelial cell. In macrophages, the production of nitric oxide, PGE2, cytokines and ILs (TNF-α, IL-1β, IL-6, IL-12), which reflects chronic inflammatory processes, was reduced. Adenosine was identified as the main bioactive of TAE. Thus, TAE had cell-specific and context-dependent effects. We infer from these in vitro data, that during acute inflammation TAE enhances cellular alertness and therefore the sensing of disturbed immune homeostasis in the vascular-endothelial compartment. Conversely, it blunts inflammatory mediators in macrophages during chronic inflammation. A novel concept of immune regulation by this extract is proposed. PMID:26840280

  2. Mast cells as modulators of hair follicle cycling.

    Science.gov (United States)

    Maurer, M; Paus, R; Czarnetzki, B M

    1995-08-01

    While the central role of mast cells (MC) in allergy and inflammation is well-appreciated, much less is known about their physiological functions. The impressive battery of potent growth modulatory MC products, and increasing evidence of MC involvement in hyperproliferative and fibrotic disorders suggest that tissue remodelling may be one of those, namely in the skin. Here, we delineate why this may best be studied by analysing the potential role of MC in hair growth regulation. On the background of numerous, yet widely under-appreciated hints from the older literature, we summarize and discuss our recent observations from the C57BL/6 mouse model for hair research which support the concept that MC are functionally important modulators of hair follicle cycling, specifically during anagen development. This invites to exploit the murine hair cycle as a model for dissecting the physiological growth modulatory functions of MC and encourages the exploration of MC-targeting pharmaceutical strategies for the treatment of hair growth disorders.

  3. DNA Damage in Inflammation-Related Carcinogenesis and Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Shiho Ohnishi

    2013-01-01

    Full Text Available Infection and chronic inflammation have been recognized as important factors for carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS and reactive nitrogen species (RNS are generated from inflammatory and epithelial cells and result in oxidative and nitrative DNA damage, such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG and 8-nitroguanine. The DNA damage can cause mutations and has been implicated in the initiation and/or promotion of inflammation-mediated carcinogenesis. It has been estimated that various infectious agents are carcinogenic to humans (IARC group 1, including parasites (Schistosoma haematobium (SH and Opisthorchis viverrini (OV, viruses (hepatitis C virus (HCV, human papillomavirus (HPV, and Epstein-Barr virus (EBV, and bacterium Helicobacter pylori (HP. SH, OV, HCV, HPV, EBV, and HP are important risk factors for bladder cancer, cholangiocarcinoma, hepatocellular carcinoma, cervical cancer, nasopharyngeal carcinoma, and gastric cancer, respectively. We demonstrated that 8-nitroguanine was strongly formed via inducible nitric oxide synthase (iNOS expression at these cancer sites of patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in SH-associated bladder cancer tissues and in Oct3/4- and CD133-positive stem cells in OV-associated cholangiocarcinoma tissues. Therefore, it is considered that oxidative and nitrative DNA damage in stem cells may play a key role in inflammation-related carcinogenesis.

  4. Avian Influenza Viruses, Inflammation, and CD8+ T Cell Immunity

    Science.gov (United States)

    Wang, Zhongfang; Loh, Liyen; Kedzierski, Lukasz; Kedzierska, Katherine

    2016-01-01

    Avian influenza viruses (AIVs) circulate naturally in wild aquatic birds, infect domestic poultry, and are capable of causing sporadic bird-to-human transmissions. AIVs capable of infecting humans include a highly pathogenic AIV H5N1, first detected in humans in 1997, and a low pathogenic AIV H7N9, reported in humans in 2013. Both H5N1 and H7N9 cause severe influenza disease in humans, manifested by acute respiratory distress syndrome, multi-organ failure, and high mortality rates of 60% and 35%, respectively. Ongoing circulation of H5N1 and H7N9 viruses in wild birds and poultry, and their ability to infect humans emphasizes their epidemic and pandemic potential and poses a public health threat. It is, thus, imperative to understand the host immune responses to the AIVs so we can control severe influenza disease caused by H5N1 or H7N9 and rationally design new immunotherapies and vaccines. This review summarizes our current knowledge on AIV epidemiology, disease symptoms, inflammatory processes underlying the AIV infection in humans, and recent studies on universal pre-existing CD8+ T cell immunity to AIVs. Immune responses driving the host recovery from AIV infection in patients hospitalized with severe influenza disease are also discussed. PMID:26973644

  5. Self-antigen recognition by TGFβ1-deficient T cells causes their activation and systemic inflammation

    OpenAIRE

    Bommireddy, Ramireddy; Pathak, Leena J; Martin, Jennifer; Ormsby, Ilona; Engle, Sandra J; Gregory P. Boivin; Babcock, George F.; Eriksson, Anna U.; Singh, Ram R; DOETSCHMAN, THOMAS

    2006-01-01

    To investigate whether the multifocal inflammatory disease in TGFβ1-deficient mice is caused by self-antigen (self-Ag)-specific autoreactive T cells, or whether it is caused by antigen independent, spontaneous hyperactivation of T cells, we have generated Tgfb1−/− and Tgfb1−/− Rag1−/− mice expressing the chicken OVA-specific TCR transgene (DO11.10). On a Rag1-sufficient background, Tgfb1−/− DO11.10 mice develop a milder inflammation than do Tgfb1−/− mice, and their T cells display a less acti...

  6. Pancreatic β-cells activate a JunB/ATF3-dependent survival pathway during inflammation

    DEFF Research Database (Denmark)

    Gurzov, E N; Barthson, J; Marhfour, I;

    2012-01-01

    Destruction of insulin-producing pancreatic β-cells by local autoimmune inflammation is a hallmark of type 1 diabetes. Histochemical analysis of pancreases from non-obese diabetic mice indicated activation of the transcription factor JunB/AP-1 (activator protein-1) after autoimmune infiltration...... nearly 20% of the cytokine-modified β-cell genes, including the transcription factor ATF3. Direct transcriptional induction of ATF3 by JunB is a key event for β-cell survival after TNF-α+IFN-γ treatment. Moreover, pharmacological upregulation of JunB/ATF3 via increased cAMP protected rodent primary β...

  7. Gut microbiota-derived short-chain Fatty acids, T cells, and inflammation.

    Science.gov (United States)

    Kim, Chang H; Park, Jeongho; Kim, Myunghoo

    2014-12-01

    T cells are central players in the regulation of adaptive immunity and immune tolerance. In the periphery, T cell differentiation for maturation and effector function is regulated by a number of factors. Various factors such as antigens, co-stimulation signals, and cytokines regulate T cell differentiation into functionally specialized effector and regulatory T cells. Other factors such as nutrients, micronutrients, nuclear hormones and microbial products provide important environmental cues for T cell differentiation. A mounting body of evidence indicates that the microbial metabolites short-chain fatty acids (SCFAs) have profound effects on T cells and directly and indirectly regulate their differentiation. We review the current status of our understanding of SCFA functions in regulation of peripheral T cell activity and discuss their impact on tissue inflammation. PMID:25550694

  8. Modulation of host cell signaling pathways as a therapeutic approach in periodontal disease

    Directory of Open Access Journals (Sweden)

    João Antonio Chaves de Souza

    2012-04-01

    Full Text Available Recently, new treatment approaches have been developed to target the host component of periodontal disease. This review aims at providing updated information on host-modulating therapies, focusing on treatment strategies for inhibiting signal transduction pathways involved in inflammation. Pharmacological inhibitors of MAPK, NFκB and JAK/STAT pathways are being developed to manage rheumatoid arthritis, periodontal disease and other inflammatory diseases. Through these agents, inflammatory mediators can be inhibited at cell signaling level, interfering on transcription factors activation and inflammatory gene expression. Although these drugs offer great potential to modulate host response, their main limitations are lack of specificity and developments of side effects. After overcoming these limitations, adjunctive host modulating drugs will provide new therapeutic strategies for periodontal treatment.

  9. Iron-ascorbate-mediated lipid peroxidation causes epigenetic changes in the antioxidant defense in intestinal epithelial cells: impact on inflammation.

    Directory of Open Access Journals (Sweden)

    Sabrina Yara

    Full Text Available INTRODUCTION: The gastrointestinal tract is frequently exposed to noxious stimuli that may cause oxidative stress, inflammation and injury. Intraluminal pro-oxidants from ingested nutrients especially iron salts and ascorbic acid frequently consumed together, can lead to catalytic formation of oxygen-derived free radicals that ultimately overwhelm the cellular antioxidant defense and lead to cell damage. HYPOTHESIS: Since the mechanisms remain sketchy, efforts have been exerted to evaluate the role of epigenetics in modulating components of endogenous enzymatic antioxidants in the intestine. To this end, Caco-2/15 cells were exposed to the iron-ascorbate oxygen radical-generating system. RESULTS: Fe/Asc induced a significant increase in lipid peroxidation as reflected by the elevated formation of malondialdehyde along with the alteration of antioxidant defense as evidenced by raised superoxide dismutase 2 (SOD2 and diminished glutathione peroxidase (GPx activities and genes. Consequently, there was an up-regulation of inflammatory processes illustrated by the activation of NF-κB transcription factor, the higher production of interleukin-6 and cycloxygenase-2 as well as the decrease of IκB. Assessment of promoter's methylation revealed decreased levels for SOD2 and increased degree for GPx2. On the other hand, pre-incubation of Caco-2/15 cells with 5-Aza-2'-deoxycytidine, a demethylating agent, or Trolox antioxidant normalized the activities of SOD2 and GPx, reduced lipid peroxidation and prevented inflammation. CONCLUSION: Redox and inflammatory modifications in response to Fe/Asc -mediated lipid peroxidation may implicate epigenetic methylation.

  10. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1.

    OpenAIRE

    Pillay, J.; Kamp, V.M.; van Hoffen, E; Visser, T.; Tak, T; Lammers, J. W.; Ulfman, L.H.; Leenen, L.P.H.; Pickkers, P; Koenderman, L

    2012-01-01

    Suppression of immune responses is necessary to limit damage to host tissue during inflammation, but it can be detrimental in specific immune responses, such as sepsis and antitumor immunity. Recently, immature myeloid cells have been implicated in the suppression of immune responses in mouse models of cancer, infectious disease, bone marrow transplantation, and autoimmune disease. Here, we report the identification of a subset of mature human neutrophils (CD11cbright/CD62Ldim/CD11bbright/CD1...

  11. Sterile inflammation – do innate lymphoid cell subsets play a role?

    OpenAIRE

    Shane E Russell; Walsh, Patrick T.

    2012-01-01

    The recent identification of several novel innate lymphoid cell (iLC) subsets has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets toward the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent studies have hi...

  12. Sterile Inflammation-Do innate lymphoid cell subsets play a role?

    OpenAIRE

    Shane E Russell; Walsh, Patrick T.

    2012-01-01

    The recent identification of several novel innate lymphoid cell subsets (iLCs) has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets towards the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent studies have ...

  13. Sollar cell module; Taiyo denchi mojuru

    Energy Technology Data Exchange (ETDEWEB)

    Komori, A.; Mori, T.; Shiotsuka, H.; Kataoka, I.; Yamada, S.

    1997-02-25

    This invention relates to a solar cell module composed of a photovoltaic device with at least one layer of a semiconductor photoactive layer as a photoelectric conversion material and a covering material, in which thermoplastic transparent organic polymer resin of a gel fraction more than 80% is used as the covering material. This polymer resin has a diminution rate of ultraviolet absorption between 5 and 50% when exposed to an atmosphere of a temperature of 150{degree}C for 72 hours. The thermoplastic transparent polymer resin of a gel fraction more than 80% is cross-linked sufficiently and is hard to deteriorate. Therefore, the adhesion between the thermoplastic transparent polymer resin and the uppermost resin film is secured owing to no emergence of the glass fiber and moreover, reinforcement of the thermoplastic transparent polymer resin with glass fiber enable to reduce the thickness of the thermoplastic transparent polymer resin while securing the scratch resistance. 6 figs., 1 tab.

  14. Role of gamma-delta T cells in liver inflammation and fibrosis

    Institute of Scientific and Technical Information of China (English)

    Linda; Hammerich; Frank; Tacke

    2014-01-01

    Conventional adaptive T cell responses contribute to liver inflammation and fibrogenesis,especially in chronic viral infections and autoimmune hepatitis.However,the role of unconventional gamma-delta(γδ)T cells in liver diseases is less clear.In the past two decades,accumulating evidence revealed thatγδT cell numbers remarkably increase in the liver upon various inflammatory conditions in mice and humans.More recent studies demonstrated that the functional effect ofγδT cells on liver disease progression depends on the subsets involved,which can be identified by the expression of distinct T cell receptor chains and of specific cytokines.Fascinatingly,γδT cells may have protective as well as pathogenic functions in liver diseases.Interferonγ-producingγδT cells,for example,induce apoptosis in hepatocytes but also in hepatic tumor cells;while interleukin-17-expressingγδT cells can downregulate pathogenic effector functions of other immune cells and can promote apoptosis of fibrogenic stellate cells.However,the results obtained in human liver disease as well as murine models are not fully conclusive at present,and the effects ofγδT cells on the outcome of liver disease might vary dependent on etiology and stage of disease.Further definitions of theγδT cell subsets in-volved in acute and chronic liver inflammation,as well as their effector cytokines might uncover whether interference withγδT cells could be a useful target for the treatment of liver disease.

  15. Adipose-Derived Stem Cells Ameliorate Allergic Airway Inflammation by Inducing Regulatory T Cells in a Mouse Model of Asthma

    Directory of Open Access Journals (Sweden)

    Kyu-Sup Cho

    2014-01-01

    Full Text Available Although several studies have demonstrated that mesenchymal stem cells derived from adipose tissue (ASCs can ameliorate allergic airway inflammation, the immunomodulatory mechanism of ASCs remains unclear. In this study, we investigated whether regulatory T cells (Tregs induction is a potential mechanism in immunomodulatory effects of ASCs on allergic airway disease and how these induced Tregs orchestrate allergic inflammation. Intravenous administration of ASCs significantly reduced allergic symptoms and inhibited eosinophilic inflammation. Airway hyperresponsiveness, total immune cell and eosinophils in the bronchoalveolar lavage fluid, mucus production, and serum allergen-specific IgE and IgG1 were significantly reduced after ASCs administration. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13 and enhanced Th1 cytokine (IFN-γ and regulatory cytokines (IL-10 and TGF-β in the bronchoalveolar lavage fluid and lung draining lymph nodes. Furthermore, levels of IDO, TGF-β, and PGE2 were significantly increased after ASCs administration. Interestingly, this upregulation was accompanied by increased Treg populations. In conclusion, ASCs ameliorated allergic airway inflammation and improved lung function through the induction of Treg expansion. The induction of Treg by ASCs involves the secretion of soluble factors such as IDO, TGF-β, and PGE2 and Treg might be involved in the downregulation of Th2 cytokines and upregulation of Th1 cytokines production.

  16. Adipose-derived stem cells ameliorate allergic airway inflammation by inducing regulatory T cells in a mouse model of asthma.

    Science.gov (United States)

    Cho, Kyu-Sup; Park, Mi-Kyung; Kang, Shin-Ae; Park, Hee-Young; Hong, Sung-Lyong; Park, Hye-Kyung; Yu, Hak-Sun; Roh, Hwan-Jung

    2014-01-01

    Although several studies have demonstrated that mesenchymal stem cells derived from adipose tissue (ASCs) can ameliorate allergic airway inflammation, the immunomodulatory mechanism of ASCs remains unclear. In this study, we investigated whether regulatory T cells (Tregs) induction is a potential mechanism in immunomodulatory effects of ASCs on allergic airway disease and how these induced Tregs orchestrate allergic inflammation. Intravenous administration of ASCs significantly reduced allergic symptoms and inhibited eosinophilic inflammation. Airway hyperresponsiveness, total immune cell and eosinophils in the bronchoalveolar lavage fluid, mucus production, and serum allergen-specific IgE and IgG1 were significantly reduced after ASCs administration. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the bronchoalveolar lavage fluid and lung draining lymph nodes. Furthermore, levels of IDO, TGF-β, and PGE2 were significantly increased after ASCs administration. Interestingly, this upregulation was accompanied by increased Treg populations. In conclusion, ASCs ameliorated allergic airway inflammation and improved lung function through the induction of Treg expansion. The induction of Treg by ASCs involves the secretion of soluble factors such as IDO, TGF-β, and PGE2 and Treg might be involved in the downregulation of Th2 cytokines and upregulation of Th1 cytokines production. PMID:25246732

  17. Hypercholesterolemia Tunes Hematopoietic Stem/Progenitor Cells for Inflammation and Atherosclerosis.

    Science.gov (United States)

    Ma, Xiaojuan; Feng, Yingmei

    2016-01-01

    As the pathological basis of cardiovascular disease (CVD), atherosclerosis is featured as a chronic inflammation. Hypercholesterolemia is an independent risk factor for CVD. Accumulated studies have shown that hypercholesterolemia is associated with myeloid cell expansion, which stimulates innate and adaptive immune responses, strengthens inflammation, and accelerates atherosclerosis progression. Hematopoietic stem/progenitor cells (HSPC) in bone marrow (BM) expresses a panel of lipoprotein receptors to control cholesterol homeostasis. Deficiency of these receptors abrogates cellular cholesterol efflux, resulting in HSPC proliferation and differentiation in hypercholesterolemic mice. Reduction of the cholesterol level in the lipid rafts by infusion of reconstituted high-density lipoprotein (HDL) or its major apolipoprotein, apoA-I, reverses hypercholesterolemia-induced HSPC expansion. Apart from impaired cholesterol metabolism, inhibition of reactive oxygen species production suppresses HSPC activation and leukocytosis. These data indicate that the mechanisms underlying the effects of hypercholesterolemia on HSPC proliferation and differentiation could be multifaceted. Furthermore, dyslipidemia also regulates HSPC-neighboring cells, resulting in HSPC mobilization. In the article, we review how hypercholesterolemia evokes HSPC activation and mobilization directly or via its modification of BM microenvironment. We hope this review will bring light to finding key molecules to control HSPC expansion, inflammation, and atherosclerosis for the treatment of CVD. PMID:27447612

  18. Self-glycolipids modulate dendritic cells changing the cytokine profiles of committed autoreactive T cells.

    Directory of Open Access Journals (Sweden)

    Karsten Buschard

    Full Text Available The impact of glycolipids of non-mammalian origin on autoimmune inflammation has become widely recognized. Here we report that the naturally occurring mammalian glycolipids, sulfatide and β-GalCer, affect the differentiation and the quality of antigen presentation by monocyte-derived dendritic cells (DCs. In response to sulfatide and β-GalCer, monocytes develop into immature DCs with higher expression of HLA-DR and CD86 but lower expression of CD80, CD40 and CD1a and lower production of IL-12 compared to non-modulated DCs. Self-glycolipid-modulated DCs responded to lipopolysaccharide (LPS by changing phenotype but preserved low IL-12 production. Sulfatide, in particular, reduced the capacity of DCs to stimulate autoreactive Glutamic Acid Decarboxylase (GAD65 - specific T cell response and promoted IL-10 production by the GAD65-specific clone. Since sulfatide and β-GalCer induced toll-like receptor (TLR-mediated signaling, we hypothesize that self-glycolipids deliver a (tolerogenic polarizing signal to differentiating DCs, facilitating the maintenance of self-tolerance under proinflammatory conditions.

  19. Interactions between endothelial cells and T cells modulate responses to mixed neutron/gamma radiation.

    Science.gov (United States)

    Cary, Lynnette H; Noutai, Daniel; Salber, Rudolph E; Williams, Margaret S; Ngudiankama, Barbara F; Whitnall, Mark H

    2014-06-01

    Detonation of an improvised nuclear device near a population center would cause significant casualties from the acute radiation syndrome (ARS) due to exposure to mixed neutron/gamma fields (MF). The pathophysiology of ARS involves inflammation, microvascular damage and alterations in immune function. Interactions between endothelial cells (EC) and hematopoietic cells are important not only for regulating immune cell traffic and function, but also for providing the microenvironment that controls survival, differentiation and migration of hematopoietic stem and progenitor cells in blood-forming tissues. Endothelial cells/leukocyte interactions also influence tumor progression and the results of anticancer therapies. In this study, we hypothesized that irradiation of endothelial cells would modulate their effects on hematopoietic cells and vice versa. Human umbilical vein endothelial cells (HUVEC) and immortalized T lymphocytes (Jurkat cells) were cultured individually and in co-culture after exposure to mixed fields. Effects of nonirradiated cells were compared to effects of irradiated cells and alterations in signaling pathways were determined. Mitogen-activated protein kinases (MAPKs) p38 and p44/42 (ERK1/2) in HUVEC exhibited higher levels of phosphorylated protein after exposure to mixed field radiation. IL-6, IL-8, G-CSF, platelet derived growth factor (PDGF) and angiopoietin 2 (ANG2) protein expression were upregulated in HUVEC by exposure to mixed field radiation. PCR arrays using HUVEC mRNA revealed alterations in gene expression after exposure to mixed fields and/or co-culture with Jurkat cells. The presence of HUVEC also influenced the function of Jurkat cells. Nonirradiated Jurkat cells showed an increase in proliferation when co-cultured with nonirradiated HUVEC, and a decrease in proliferation when co-cultured with irradiated HUVEC. Additionally, nonirradiated Jurkat cells incubated in media from irradiated HUVEC exhibited upregulation of activated

  20. Cerebrospinal fluid B cells correlate with early brain inflammation in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Bettina Kuenz

    Full Text Available BACKGROUND: There is accumulating evidence from immunological, pathological and therapeutic studies that B cells are key components in the pathophysiology of multiple sclerosis (MS. METHODOLOGY/PRINCIPAL FINDINGS: In this prospective study we have for the first time investigated the differences in the inflammatory response between relapsing and progressive MS by comparing cerebrospinal fluid (CSF cell profiles from patients at the onset of the disease (clinically isolated syndrome, CIS, relapsing-remitting (RR and chronic progressive (CP MS by flow cytometry. As controls we have used patients with other neurological diseases. We have found a statistically significant accumulation of CSF mature B cells (CD19+CD138- and plasma blasts (CD19+CD138+ in CIS and RRMS. Both B cell populations were, however, not significantly increased in CPMS. Further, this accumulation of B cells correlated with acute brain inflammation measured by magnetic resonance imaging and with inflammatory CSF parameters such as the number of CSF leukocytes, intrathecal immunoglobulin M and G synthesis and intrathecal production of matrix metalloproteinase (MMP-9 and the B cell chemokine CxCL-13. CONCLUSIONS: Our data support an important role of CSF B cells in acute brain inflammation in CIS and RRMS.

  1. Involvement of Ubiquitin-Editing Protein A20 in Modulating Inflammation in Rat Cochlea Associated with Silver Nanoparticle-Induced CD68 Upregulation and TLR4 Activation

    Science.gov (United States)

    Feng, Hao; Pyykkö, Ilmari; Zou, Jing

    2016-05-01

    Silver nanoparticles (AgNPs) were shown to temporarily impair the biological barriers in the skin of the external ear canal, mucosa of the middle ear, and inner ear, causing partially reversible hearing loss after delivery into the middle ear. The current study aimed to elucidate the molecular mechanism, emphasizing the TLR signaling pathways in association with the potential recruitment of macrophages in the cochlea and the modulation of inflammation by ubiquitin-editing protein A20. Molecules potentially involved in these signaling pathways were thoroughly analysed using immunohistochemistry in the rat cochlea exposed to AgNPs at various concentrations through intratympanic injection. The results showed that 0.4 % AgNPs but not 0.02 % AgNPs upregulated the expressions of CD68, TLR4, MCP1, A20, and RNF11 in the strial basal cells, spiral ligament fibrocytes, and non-sensory supporting cells of Corti's organ. 0.4 % AgNPs had no effect on CD44, TLR2, MCP2, Rac1, myosin light chain, VCAM1, Erk1/2, JNK, p38, IL-1β, TNF-α, TNFR1, TNFR2, IL-10, or TGF-β. This study suggested that AgNPs might confer macrophage-like functions on the strial basal cells and spiral ligament fibrocytes and enhance the immune activities of non-sensory supporting cells of Corti's organ through the upregulation of CD68, which might be involved in TLR4 activation. A20 and RNF11 played roles in maintaining cochlear homeostasis via negative regulation of the expressions of inflammatory cytokines.

  2. Involvement of Ubiquitin-Editing Protein A20 in Modulating Inflammation in Rat Cochlea Associated with Silver Nanoparticle-Induced CD68 Upregulation and TLR4 Activation.

    Science.gov (United States)

    Feng, Hao; Pyykkö, Ilmari; Zou, Jing

    2016-12-01

    Silver nanoparticles (AgNPs) were shown to temporarily impair the biological barriers in the skin of the external ear canal, mucosa of the middle ear, and inner ear, causing partially reversible hearing loss after delivery into the middle ear. The current study aimed to elucidate the molecular mechanism, emphasizing the TLR signaling pathways in association with the potential recruitment of macrophages in the cochlea and the modulation of inflammation by ubiquitin-editing protein A20. Molecules potentially involved in these signaling pathways were thoroughly analysed using immunohistochemistry in the rat cochlea exposed to AgNPs at various concentrations through intratympanic injection. The results showed that 0.4 % AgNPs but not 0.02 % AgNPs upregulated the expressions of CD68, TLR4, MCP1, A20, and RNF11 in the strial basal cells, spiral ligament fibrocytes, and non-sensory supporting cells of Corti's organ. 0.4 % AgNPs had no effect on CD44, TLR2, MCP2, Rac1, myosin light chain, VCAM1, Erk1/2, JNK, p38, IL-1β, TNF-α, TNFR1, TNFR2, IL-10, or TGF-β. This study suggested that AgNPs might confer macrophage-like functions on the strial basal cells and spiral ligament fibrocytes and enhance the immune activities of non-sensory supporting cells of Corti's organ through the upregulation of CD68, which might be involved in TLR4 activation. A20 and RNF11 played roles in maintaining cochlear homeostasis via negative regulation of the expressions of inflammatory cytokines. PMID:27142878

  3. Alveolar macrophages modulate allergic inflammation in a murine model of asthma

    OpenAIRE

    Bang, Bo-Ram; Chun, Eunyoung; Shim, Eun-Jin; Lee, Hyun-Seung; Lee, Soo-Yeon; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Park, Heung-Woo

    2011-01-01

    The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Pheno...

  4. Clozapine-induced mitochondria alterations and inflammation in brain and insulin-responsive cells.

    Directory of Open Access Journals (Sweden)

    Verόnica Contreras-Shannon

    Full Text Available BACKGROUND: Metabolic syndrome (MetS is a constellation of factors including abdominal obesity, hyperglycemia, dyslipidemias, and hypertension that increase morbidity and mortality from diabetes and cardiovascular diseases and affects more than a third of the population in the US. Clozapine, an atypical antipsychotic used for the treatment of schizophrenia, has been found to cause drug-induced metabolic syndrome (DIMS and may be a useful tool for studying cellular and molecular changes associated with MetS and DIMS. Mitochondria dysfunction, oxidative stress and inflammation are mechanisms proposed for the development of clozapine-related DIMS. In this study, the effects of clozapine on mitochondrial function and inflammation in insulin responsive and obesity-associated cultured cell lines were examined. METHODOLOGY/PRINCIPAL FINDINGS: Cultured mouse myoblasts (C2C12, adipocytes (3T3-L1, hepatocytes (FL-83B, and monocytes (RAW 264.7 were treated with 0, 25, 50 and 75 µM clozapine for 24 hours. The mitochondrial selective probe TMRM was used to assess membrane potential and morphology. ATP levels from cell lysates were determined by bioluminescence assay. Cytokine levels in cell supernatants were assessed using a multiplex array. Clozapine was found to alter mitochondria morphology, membrane potential, and volume, and reduce ATP levels in all cell lines. Clozapine also significantly induced the production of proinflammatory cytokines IL-6, GM-CSF and IL12-p70, and this response was particularly robust in the monocyte cell line. CONCLUSIONS/SIGNIFICANCE: Clozapine damages mitochondria and promotes inflammation in insulin responsive cells and obesity-associated cell types. These phenomena are closely associated with changes observed in human and animal studies of MetS, obesity, insulin resistance, and diabetes. Therefore, the use of clozapine in DIMS may be an important and relevant tool for investigating cellular and molecular changes associated

  5. The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation.

    Science.gov (United States)

    Grabiec, Aleksander M; Hussell, Tracy

    2016-07-01

    Acute and chronic inflammatory responses in the lung are associated with the accumulation of large quantities of immune and structural cells undergoing apoptosis, which need to be engulfed by phagocytes in a process called 'efferocytosis'. Apoptotic cell recognition and removal from the lung is mediated predominantly by airway macrophages, though immature dendritic cells and non-professional phagocytes, such as epithelial cells and mesenchymal cells, can also display this function. Efficient clearance of apoptotic cells from the airways is essential for successful resolution of inflammation and the return to lung homeostasis. Disruption of this process leads to secondary necrosis of accumulating apoptotic cells, release of necrotic cell debris and subsequent uncontrolled inflammatory activation of the innate immune system by the released 'damage associated molecular patterns' (DAMPS). To control the duration of the immune response and prevent autoimmune reactions, anti-inflammatory signalling cascades are initiated in the phagocyte upon apoptotic cell uptake, mediated by a range of receptors that recognise specific phospholipids or proteins externalised on, or secreted by, the apoptotic cell. However, prolonged activation of apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl and MerTK (TAM), may delay or prevent inflammatory responses to subsequent infections. In this review, we will discuss recent advances in our understanding of the mechanism controlling apoptotic cell recognition and removal from the lung in homeostasis and during inflammation, the contribution of defective efferocytosis to chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease, asthma and cystic fibrosis, and implications of the signals triggered by apoptotic cells in the susceptibility to pulmonary microbial infections. PMID:26957481

  6. T cells are necessary for ILC2 activation in house dust mite-induced allergic airway inflammation in mice.

    Science.gov (United States)

    Li, Bobby W S; de Bruijn, Marjolein J W; Tindemans, Irma; Lukkes, Melanie; KleinJan, Alex; Hoogsteden, Henk C; Hendriks, Rudi W

    2016-06-01

    Allergic asthma is a chronic inflammation of the airways mediated by an adaptive type 2 immune response. Upon allergen exposure, group 2 innate lymphoid cells (ILC2s) can be rapidly activated and represent an early innate source of IL-5 and IL-13. Here, we used a house dust mite (HDM)-driven asthma mouse model to study the induction of ILC2s in allergic airway inflammation. In BALF, lungs, and lymph nodes, ILC2 activation is critically dependent on prior sensitization with HDM. Importantly, T cells are required for ILC2 induction, whereby T-cell activation precedes ILC2 induction. During HDM-driven allergic airway inflammation the accumulation of ILC2s in BALF is IL-33 independent, although infiltrating ILC2s produce less cytokines in Il33(-/-) mice. Transfer of in vitro polarized OVA-specific OT-II Th2 cells alone or in combination with Th17 cells followed by OVA and HDM challenge is not sufficient to induce ILC2, despite significant eosinophilic inflammation and T-cell activation. In this asthma model, ILC2s are therefore not an early source of Th2 cytokines, but rather contribute to type 2 inflammation in which Th2 cells play a key role. Taken together, ILC2 induction in HDM-mediated allergic airway inflammation in mice critically depends on activation of T cells. PMID:27062360

  7. Capsaicinoids cause inflammation and epithelial cell death through activation of vanilloid receptors.

    Science.gov (United States)

    Reilly, Christopher A; Taylor, Jack L; Lanza, Diane L; Carr, Brian A; Crouch, Dennis J; Yost, Garold S

    2003-05-01

    Capsaicinoids, found in less-than-lethal self-defense weapons, have been associated with respiratory failure and death in exposed animals and people. The studies described herein provide evidence for acute respiratory inflammation and damage to epithelial cells in experimental animals, and provide precise molecular mechanisms that mediate these effects using human bronchiolar and alveolar epithelial cells. Inhalation exposure of rats to pepper sprays (capsaicinoids) produced acute inflammation and damage to nasal, tracheal, bronchiolar, and alveolar cells in a dose-related manner. In vitro cytotoxicity assays demonstrated that cultured human lung cells (BEAS-2B and A549) were more susceptible to necrotic cell death than liver (HepG2) cells. Transcription of the human vanilloid receptor type-1, VR1 or TRPV1, was demonstrated by RT-PCR in all of these cells, and the relative transcript levels were correlated to cellular susceptibility. TRPV1 receptor activation was presumably responsible for cellular cytotoxicity, but prototypical functional antagonists of this receptor were cytotoxic themselves, and did not ameliorate capsaicinoid-induced damage. Conversely, the TRPV1 antagonist capsazepine, as well as calcium chelation by EGTA ablated cytokine (IL-6) production after capsaicin exposure. To address these seemingly contradictory results, recombinant human TRPV1 was cloned and overexpressed in BEAS-2B cells. These cells exhibited dramatically increased cellular susceptibility to capsaicinoids, measured using IL-6 production and cytotoxicity, and an apoptotic mechanism of cell death. Surprisingly, the cytotoxic effects of capsaicin in TRPV1 overexpressing cells were also not inhibited by TRPV1 antagonists or by treatments that modified extracellular calcium. Thus, capsaicin interacted with TRPV1 expressed by BEAS-2B and other airway epithelial cells to cause the calcium-dependent production of cytokines and, conversely, calcium-independent cell death. These results

  8. The Emerging Roles of Gamma–Delta T Cells in Tissue Inflammation in Experimental Autoimmune Encephalomyelitis

    Science.gov (United States)

    Malik, Sakshi; Want, Muzamil Yaqub; Awasthi, Amit

    2016-01-01

    γδ (gamma–delta) T cells, a small population of unconventional T cells, have been found in central nervous system lesions of multiple sclerosis (MS) patients, but their function in disease activity is not clearly understood. Previous studies in experimental autoimmune encephalomyelitis (EAE) were inconsistent in identifying their specific roles in suppressing or promoting disease pathogenesis. Emerging advancements in the biology of γδ T cells especially in the context of their being the major initial producers of IL-17, suggested their crucial role in pathogenesis of EAE. In addition, γδ T cells express high levels of IL-23R and IL-1R, which further enhance their effector functions in the pathogenesis of EAE. Nonetheless, activated heterogeneous γδ T cells display functional dichotomy, which is crucial in determining the outcomes of tissue inflammation in EAE. In this review, we discussed recent advances in understanding the biology of γδ T cells in tissue inflammation as well as their roles in suppressing or promoting the development of EAE. PMID:26858718

  9. Cell-permeable Tat-NBD peptide attenuates rat pancreatitis and acinus cell inflammation response

    Institute of Scientific and Technical Information of China (English)

    You-Ming Long; Ken Chen; Xue-Jin Liu; Wen-Rui Xie; Hui Wang

    2009-01-01

    AIM: To investigate the effects of Tat-NEMO-binding domain (NBD) peptide on taurocholate-induced pancreatitis and lipopolysaccharide (LPS)-stimulated AR42J acinus cells inflammatory response in rats. METHODS: Sodium taurocholate (5%) was used to induce the pancreatitis model. Forty-eight rats from the taurocholate group aeceuved an intravenous bolus of 13 mg/kg Tat-NBD (wild-type, WT) peptide, Tat-NBD (mutant-type, MT) peptide, NBD peptide or Tat peptide. The pancreatic histopathology was analyzed by hematoxylin staining. LPS was added to the culture medium to stimulate the AR42J cells. For pretreatment, cells were incubated with different peptides for 2 h before LPS stimulation. Expression of IL-1β and TNF-α mRNA was analyzed using a semi-quantitative reverse-transcript polymerase chain reaction (RT-PCR) method. IL-1β and TNF-α protein in culture medium were detected by enzyme linked immunosorbent assay (ELISA). NF-κB DNA-binding in pancreas was examined by electrophoretic mobility shift assays. P65 expression of AR42J was determined by Strept Actividin-Biotin Complex (SABC) method. RESULTS: Pretreatment with Tat-NBD (WT) peptide at a concentration of 13 mg/kg body wt showed beneficial effect in pancreaitis model. LPS (10 mg/L) resulted in an increase of IL-1β mRNA, IL-1β protein, TNF-α mRNA and TNF-α protein, whereas significantly inhibitory effects were observed when cells were incubated with Tat-NBD (WT). Consisting with p65 expression decrease analyzed by SABC method, NF-κB DNA-binding activity significantly decreased in Tat-NBD (WT) pretreatment group, especially at the largest dose. No significant changes were found in the control peptide group. CONCLUSION: Our result supports that active NF-κB participates in the pathogenesis of STC-induced acute pancreatitis in rats. Tat-NBD (WT) peptide has antiinflammatory effects in this model and inhibits the inflammation of acinus simulated by LPS.

  10. Emerging roles of myeloid derived suppressor cells in hepatic inflammation and fibrosis

    OpenAIRE

    Hammerich, Linda; Tacke, Frank

    2015-01-01

    Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immune cells that are potent suppressors of immune responses. MDSC emerge in various compartments in the body, such as blood, bone marrow or spleen, especially in conditions of cancer, infections or inflammation. MDSC usually express CD11b, CD33, and low levels of human leukocyte antigen-DR in humans or CD11b and Gr1 (Ly6C/G) in mice, and they can be further divided into granulocytic or monocytic MDSC. The liver is an i...

  11. The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation.

    Science.gov (United States)

    Zaiss, Mario M; Rapin, Alexis; Lebon, Luc; Dubey, Lalit Kumar; Mosconi, Ilaria; Sarter, Kerstin; Piersigilli, Alessandra; Menin, Laure; Walker, Alan W; Rougemont, Jacques; Paerewijck, Oonagh; Geldhof, Peter; McCoy, Kathleen D; Macpherson, Andrew J; Croese, John; Giacomin, Paul R; Loukas, Alex; Junt, Tobias; Marsland, Benjamin J; Harris, Nicola L

    2015-11-17

    Intestinal helminths are potent regulators of their host's immune system and can ameliorate inflammatory diseases such as allergic asthma. In the present study we have assessed whether this anti-inflammatory activity was purely intrinsic to helminths, or whether it also involved crosstalk with the local microbiota. We report that chronic infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb) altered the intestinal habitat, allowing increased short chain fatty acid (SCFA) production. Transfer of the Hpb-modified microbiota alone was sufficient to mediate protection against allergic asthma. The helminth-induced anti-inflammatory cytokine secretion and regulatory T cell suppressor activity that mediated the protection required the G protein-coupled receptor (GPR)-41. A similar alteration in the metabolic potential of intestinal bacterial communities was observed with diverse parasitic and host species, suggesting that this represents an evolutionary conserved mechanism of host-microbe-helminth interactions. PMID:26522986

  12. Targeting cytosolic proliferating cell nuclear antigen (PCNA in neutrophil-dominated inflammation

    Directory of Open Access Journals (Sweden)

    Alessia eDe Chiara

    2012-10-01

    Full Text Available New therapeutic approaches that can accelerate neutrophil apoptosis under inflammatory conditions to enhance the resolution of inflammation are now under study. Neutrophils are deprived of proliferative capacity and have a tightly controlled lifespan to avoid their persistence at the site of injury. We have recently described that the proliferating cell nuclear antigen (PCNA, a nuclear factor involved in DNA replication and repair of proliferating cells is a key regulator of neutrophil survival. In this review, we will try to put into perspective the physiologic relevance of PCNA in neutrophils. We will discuss key issues such as molecular structure, post-translational modifications, based on our knowledge of nuclear PCNA, assuming that similar principles governing its function are conserved between nuclear and cytosolic PCNA. The example of cystic fibrosis that features one of the most intense neutrophil-dominated pulmonary inflammation will be discussed. We believe that through an intimate comprehension of the cytosolic PCNA scaffold based on nuclear PCNA knowledge, novel pathways regulating neutrophil survival can be unraveled and innovative agents can be developed to dampen inflammation where it proves detrimental.

  13. Modulation of Endothelial Inflammation by Low and High Magnitude Cyclic Stretch.

    Directory of Open Access Journals (Sweden)

    Yufeng Tian

    Full Text Available Excessive mechanical ventilation exerts pathologic mechanical strain on lung vascular endothelium and promotes endothelial cell (EC inflammatory activation; however, the specific mechanisms underlying EC inflammatory response caused by mechanical ventilation related cyclic stretch (CS remain unclear. This study investigated the effects of chronic exposure to CS at physiologic (5% and pathologic (18% magnitude on pulmonary EC inflammatory status in control conditions and bacterial lipopolysacharide (LPS-stimulated conditions. EC exposure to high or low CS magnitudes for 28-72 hrs had distinct effects on EC inflammatory activation. 18% CS increased surface expression of endothelial adhesion molecule ICAM1 and release of its soluble form (sICAM1 and inflammatory cytokine IL-8 by CS-stimulated pulmonary endothelial cells (EC. EC inflammatory activation was not observed in EC exposed to 5% CS. Chronic exposure to 18% CS, but not to 5% CS, augmented ICAM1 and IL-8 production and EC monolayer barrier disruption induced by LPS. 18% CS, but not 5% CS, stimulated expression of RhoA GTPase-specific guanine nucleotide exchange factor GEF-H1. GEF-H1 knockdown using gene-specific siRNA abolished 18% CS-induced ICAM1 expression and sICAM1 and IL-8 release by EC. GEF-H1 knockdown also prevented disruption of EC monolayer integrity and attenuated sICAM1 and IL-8 release in the two-hit model of EC barrier dysfunction caused by combined stimulation with 18% CS and LPS. These data demonstrate that exacerbation of inflammatory response by pulmonary endothelium exposed to excessive mechanical stretch is mediated by CS-induced induction of Rho activating protein GEF-H1.

  14. Necrosis-Induced Sterile Inflammation Mediated by Interleukin-1α in Retinal Pigment Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    Full Text Available Endogenous danger signals released from necrotic cells contribute to retinal inflammation. We have now investigated the effects of necrotic cell extracts prepared from ARPE-19 human retinal pigment epithelial cells (ANCE on the release of proinflammatory cytokines and chemokines by healthy ARPE-19 cells. ANCE were prepared by subjection of ARPE-19 cells to freeze-thaw cycles. The release of various cytokines and chemokines from ARPE-19 cells was measured with a multiplex assay system or enzyme-linked immunosorbent assays. The expression of interleukin (IL-1α and the phosphorylation and degradation of the endogenous nuclear factor-κB (NF-κB inhibitor IκB-α were examined by immunoblot analysis. Among the various cytokines and chemokines examined, we found that ANCE markedly stimulated the release of the proinflammatory cytokine IL-6 and the chemokines IL-8 and monocyte chemoattractant protein (MCP-1 by ARPE-19 cells. ANCE-induced IL-6, IL-8, and MCP-1 release was inhibited by IL-1 receptor antagonist and by an IKK2 inhibitor (a blocker of NF-κB signaling in a concentration-dependent manner, but was not affected by a pan-caspase inhibitor (Z-VAD-FMK. Recombinant IL-1α also induced the secretion of IL-6, IL-8, and MCP-1 from ARPE-19 cells, and IL-1α was detected in ANCE. Furthermore, ANCE induced the phosphorylation and degradation of IκB-α in ARPE-19 cells. Our findings thus suggest that IL-1α is an important danger signal that is released from necrotic retinal pigment epithelial cells and triggers proinflammatory cytokine and chemokine secretion from intact cells in a manner dependent on NF-κB signaling. IL-1α is therefore a potential therapeutic target for amelioration of sterile inflammation in the retina.

  15. Corrosion In Amorphous-Silicon Solar Cells And Modules

    Science.gov (United States)

    Mon, Gordon R.; Wen, Liang-Chi; Ross, Ronald G., Jr.

    1988-01-01

    Paper reports on corrosion in amorphous-silicon solar cells and modules. Based on field and laboratory tests, discusses causes of corrosion, ways of mitigating effects, and consequences for modules already in field. Suggests sealing of edges as way of reducing entry of moisture. Cell-free perimeters or sacrificial electrodes suggested to mitigate effects of sorbed moisture. Development of truly watertight module proves to be more cost-effective than attempting to mitigate effects of moisture.

  16. Application of crystalline silicon solar cells in photovoltaic modules

    OpenAIRE

    L.A. Dobrzański; A. Drygała; M. Giedroć

    2010-01-01

    Purpose: The aim of the paper is to determinate basic electrical properties of solar cells, made of them photovoltaic module and analysis of its main electrical parameters.Design/methodology/approach: In this study, several methods were used: current – voltage characteristic to determinate basic electrical properties of 36 monocrystalline silicon solar cells, soft soldering technique to bond solar cells . Photovoltaic module was produced from 31 solar cells with the largest short-circuit curr...

  17. Sterile Inflammation-Do innate lymphoid cell subsets play a role?

    Directory of Open Access Journals (Sweden)

    Shane E Russell

    2012-08-01

    Full Text Available The recent identification of several novel innate lymphoid cell subsets (iLCs has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets towards the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent studies have highlighted the role of endogenous damage associated molecular patterns such as IL-33, IL-1 and IL-1 in promoting lymphoid cell responses. This review discusses the influence of such endogenous danger signals on novel iLCs such as Lymphoid Tissue-inducer (LTi cells, innate type 2 helper cells and  T cells and explores how these responses may contribute to the development of an inflammatory response in a sterile setting.

  18. A systems model for immune cell interactions unravels the mechanism of inflammation in human skin.

    Directory of Open Access Journals (Sweden)

    Najl V Valeyev

    Full Text Available Inflammation is characterized by altered cytokine levels produced by cell populations in a highly interdependent manner. To elucidate the mechanism of an inflammatory reaction, we have developed a mathematical model for immune cell interactions via the specific, dose-dependent cytokine production rates of cell populations. The model describes the criteria required for normal and pathological immune system responses and suggests that alterations in the cytokine production rates can lead to various stable levels which manifest themselves in different disease phenotypes. The model predicts that pairs of interacting immune cell populations can maintain homeostatic and elevated extracellular cytokine concentration levels, enabling them to operate as an immune system switch. The concept described here is developed in the context of psoriasis, an immune-mediated disease, but it can also offer mechanistic insights into other inflammatory pathologies as it explains how interactions between immune cell populations can lead to disease phenotypes.

  19. Modulation of intestinal inflammation by minimal enteral nutrition with amniotic fluid in preterm pigs

    DEFF Research Database (Denmark)

    Østergaard, Mette Viberg; Bering, Stine Brandt; Jensen, Michael Ladegaard;

    2014-01-01

    Background: Necrotizing enterocolitis (NEC) is a severe inflammatory disorder, associated with the difficult transition from parenteral to enteral feeding after preterm birth. We hypothesized that minimal enteral nutrition (MEN) with amniotic fluid (AF), prior to enteral formula feeding, would...... improve resistance to NEC in preterm pigs. Methods: Experiment 1: IEC-6 cells were incubated with porcine (pAF) and human AF (hAF) to test AF-stimulated enterocyte proliferation and migration in vitro. Experiment 2: Cesarean-delivered, preterm pigs were fed parenteral nutrition and MEN with pAF, h......AF, or control fluid (MEN-pAF, MEN-hAF, or MEN-CTRL; all n = 9) for 2 days before tissue collection. Experiment 3: Preterm pigs were fed MEN diets as in experiment 2, but followed by 2 days of enteral formula feeding, which predisposes to NEC (NEC-pAF, NEC-hAF, or NEC-CTRL; n = 10-12). Results: Both pAF and h...

  20. Modulation of inflammation-related genes of polysaccharides fractionated from mycelia of medicinal basidiomycete Antrodia camphorata

    Institute of Scientific and Technical Information of China (English)

    Yen-ying WU; Chin-chu CHEN; Charng-cherng CHYAU; Sin-yi CHUNG; Yi-wen LIU

    2007-01-01

    Aim: To investigate the effect of water soluble-ethanol precipitation fraction (AC-1) and alkaline extraction-isoelectric precipitation fraction (AC-2) from Antrodia camphorata (Polyporaceae, Aphyllophorales) on lipopolysaccharide (LPS)-in-duced gene activation in mouse macrophages. Methods: The AC-1 and AC-2fractions were prepared, and their effects on LPS-induced gene expression were monitored by Western blotting and RT-PCR. Results: Our results indicated thatAC-2, but not AC-1 dose-dependently (50--200 mg/L) inhibited LPS-induced nitric oxide production as well as the protein and the mRNA expression of the inducible nitric oxide synthase (iNOS) gene. Neither AC-1 nor AC-2 inhibited LPS-inducedcyclooxygenase-2 gene expression. Using the cytokine array assay, it showed that AC-2 also had the ability to inhibit LPS-induced the protein expression of interleukin (IL)-6, IL-10, the monocyte chemoattractant protein (MCP)-5, and regulated upon activation, normal T-cell expressed, and presumably secreted (RANTES). Like iNOS, AC-2 inhibiting LPS-induced IL-6 and IL-10 secretion resulted from inhibiting their mRNA expression. Conclusion: It was suggested that alkaline extraction-isoelectric precipitated the polysaccharide fraction of A camphorata and had the ability to inhibit LPS-induced iNOS, IL-6, IL-10, MCP-5, and RANTES expression in mouse macrophages.

  1. Helicobacter pylori strain-specific modulation of gastric inflammation in Mongolian gerbils

    Institute of Scientific and Technical Information of China (English)

    Ken Ohnita; Hajime Isomoto; Shoji Honda; Akihiro Wada; Chun-Yang Wen; Yoshito Nishi; Yohei Mizuta; Toshiya Hirayama; Shigeru Kohno

    2005-01-01

    AIM: The cag pathogenicity island (PAI) is one of potential virulence determinants of Helicobacter pylori. The Mongolian gerbil is a suitable experimental animal for the screening of virulence factors of H pylori.METHODS: Five-week-old Mongolian gerbils were inoculated with a standard H pylori strain (ATCC 43504)possessing the cag PAI or a clinical isolate lacking the genes' cluster (OHPC-0002). The animals were killed at 2, 4, 8, 24 and 48 wk after inoculation (n = 5 each), and macroscopic and histopathological findings in the stomachs were compared.RESULTS: In gerbils infected with ATCC 43504, a more severe degree of infiltration of polynuclear and mononuclear cells and lymphoid follicles was observed from 4 wk after inoculation compared to gerbils infected with OHPC-0002 especially in the antrum and transitional zone from the fundic to pyloric gland area. In addition,glandular atrophy, intestinal metaplasia, gastric ulcer and hyperplastic polyps were noted in gerbils infected with ATCC 43504, whereas only mild gastric erosions occurred in those infected with OHPC-0002.CONCLUSION: Our results indicate that the cag PAI could be directly involved in gastric immune and inflammatory responses in the Mongolian gerbils, leading to a more advanced gastric disease.

  2. TLR4 signalling in pulmonary stromal cells is critical for inflammation and immunity in the airways.

    Science.gov (United States)

    Perros, Frederic; Lambrecht, Bart N; Hammad, Hamida

    2011-01-01

    Inflammation of the airways, which is often associated with life-threatening infection by Gram-negative bacteria or presence of endotoxin in the bioaerosol, is still a major cause of severe airway diseases. Moreover, inhaled endotoxin may play an important role in the development and progression of airway inflammation in asthma. Pathologic changes induced by endotoxin inhalation include bronchospasm, airflow obstruction, recruitment of inflammatory cells, injury of the alveolar epithelium, and disruption of pulmonary capillary integrity leading to protein rich fluid leak in the alveolar space. Mammalian Toll-like receptors (TLRs) are important signalling receptors in innate host defense. Among these receptors, TLR4 plays a critical role in the response to endotoxin. Lungs are a complex compartmentalized organ with separate barriers, namely the alveolar-capillary barrier, the microvascular endothelium, and the alveolar epithelium. An emerging theme in the field of lung immunology is that structural cells (SCs) of the airways such as epithelial cells (ECs), endothelial cells, fibroblasts and other stromal cells produce activating cytokines that determine the quantity and quality of the lung immune response. This review focuses on the role of TLR4 in the innate and adaptive immune functions of the pulmonary SCs. PMID:21943186

  3. Oligophrenin1 protects mice against myocardial ischemia and reperfusion injury by modulating inflammation and myocardial apoptosis.

    Science.gov (United States)

    Niermann, Christina; Gorressen, Simone; Klier, Meike; Gowert, Nina S; Billuart, Pierre; Kelm, Malte; Merx, Marc W; Elvers, Margitta

    2016-08-01

    The Rho family of small GTPases has been analyzed in cardiac physiology and pathophysiology including myocardial infarction (MI) in the last years. Contradictory results show either a protective or a declined effect of RhoA and the RhoA effector Rho-associated protein kinase (ROCK) in myocardial ischemia and reperfusion injury that is associated with cardiomyocyte survival and caspase-3 activation. Cardiac-specific deletion of Rac1 reduced ischemia reperfusion injury in diabetic hearts, whereas cardiomyocyte specific overexpression of active Rac1 predisposes the heart to increased myocardial injury with enhanced contractile dysfunction. GTPase-activating proteins (GAPs) control the activation of Rho proteins through stimulation of GTP hydrolysis. However, the impact of GAPs in myocardial ischemia and reperfusion injury remains elusive. Here we analyzed the role of oligophrenin1 (OPHN1), a RhoGAP with Bin/Amphiphysin/Rvs (BAR) domain known to regulate the activity of RhoA, Rac1 and Cdc42 in MI. The expression of Ophn1, RhoA and Rac1 is strongly upregulated 24h after myocardial ischemia. Loss of OPHN1 induced enhanced activity of Rho effector molecules leading to elevated cardiomyocyte apoptosis and increased migration of inflammatory cells into the infarct border zone of OPHN1 deficient mice. Consequently, echocardiography 24h after myocardial ischemia revealed declined left ventricle function in OPHN1 deficient mice. Our results indicate that OPHN1 mediated regulation of RhoA, Rac1 and Cdc42 is crucial for the preservation of cardiac function after myocardial injury. PMID:27117132

  4. Elevated VEGF-D Modulates Tumor Inflammation and Reduces the Growth of Carcinogen-Induced Skin Tumors.

    Science.gov (United States)

    Honkanen, Hanne-Kaisa; Izzi, Valerio; Petäistö, Tiina; Holopainen, Tanja; Harjunen, Vanessa; Pihlajaniemi, Taina; Alitalo, Kari; Heljasvaara, Ritva

    2016-07-01

    Vascular endothelial growth factor D (VEGF-D) promotes the lymph node metastasis of cancer by inducing the growth of lymphatic vasculature, but its specific roles in tumorigenesis have not been elucidated. We monitored the effects of VEGF-D in cutaneous squamous cell carcinoma (cSCC) by subjecting transgenic mice overexpressing VEGF-D in the skin (K14-mVEGF-D) and VEGF-D knockout mice to a chemical skin carcinogenesis protocol involving 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate treatments. In K14-mVEGF-D mice, tumor lymphangiogenesis was significantly increased and the frequency of lymph node metastasis was elevated in comparison with controls. Most notably, the papillomas regressed more often in K14-mVEGF-D mice than in littermate controls, resulting in a delay in tumor incidence and a remarkable reduction in the total tumor number. Skin tumor growth and metastasis were not obviously affected in the absence of VEGF-D; however, the knockout mice showed a trend for reduced lymphangiogenesis in skin tumors and in the untreated skin. Interestingly, K14-mVEGF-D mice showed an altered immune response in skin tumors. This consisted of the reduced accumulation of macrophages, mast cells, and CD4(+) T-cells and an increase of cytotoxic CD8(+) T-cells. Cytokine profiling by flow cytometry and quantitative real time PCR revealed that elevated VEGF-D expression results in an attenuated Th2 response and promotes M1/Th1 and Th17 polarization in the early stage of skin carcinogenesis, leading to an anti-tumoral immune environment and the regression of primary tumors. Our data suggest that VEGF-D may be beneficial in early-stage tumors since it suppresses the pro-tumorigenic inflammation, while at later stages VEGF-D-induced tumor lymphatics provide a route for metastasis. PMID:27435926

  5. Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis.

    Science.gov (United States)

    Klose, Christoph S N; Artis, David

    2016-06-21

    Research over the last 7 years has led to the formal identification of innate lymphoid cells (ILCs), increased the understanding of their tissue distribution and has established essential functions of ILCs in diverse physiological processes. These include resistance to pathogens, the regulation of autoimmune inflammation, tissue remodeling, cancer and metabolic homeostasis. Notably, many ILC functions appear to be regulated by mechanisms distinct from those of other innate and adaptive immune cells. In this Review, we focus on how group 2 ILC (ILC2) and group 3 ILC (ILC3) responses are regulated and how these cells interact with other immune and non-immune cells to mediate their functions. We highlight experimental evidence from mouse models and patient-based studies that have elucidated the effects of ILCs on the maintenance of tissue homeostasis and the consequences for health and disease. PMID:27328006

  6. Cell adhesion, inflammation and therapy: Old ideas and a significant step forward

    Institute of Scientific and Technical Information of China (English)

    Roberto GONZ(A)LEZ-AMARO

    2011-01-01

    Cell-to-cell adhesion as well as the interaction of cells with the extracellular matrix are key phenomena in different physiological and pathological conditions,including embryogenesis,blood coagulation,lymphocyte homing,immune response,angiogenesis,metastasis,thrombosis and inflammation[1,2].Thus,it has been widely proposed that cell adhesion molecules are an important therapeutic target in a wide array of diseases with high impact on public health,including atherosclerosis,thromboembolic disorders,cancer,graft rejection and autoimmune inflammatory conditions[1,2].However,anti-adhesion therapy with either biological agents (mainly blocking monoclonal antibodies,mAb's) or chemical inhibitors (mainly synthetic peptides) has not yet fulfilled these expectations and has not been devoid of undesirable effects[3,4

  7. Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia

    DEFF Research Database (Denmark)

    Ronit, Andreas; Plovsing, Ronni R; Gaardbo, Julie C;

    2016-01-01

    , HLA-DR(+)CD38(+) T cells were determined. Ex vivo whole-blood cytokine production and Toll-like receptor (TLR)-4 expression on Tregs were measured. Absolute number of CD3(+)CD4(+) (P = .026), CD3(+)CD8(+) (P = .046), Tregs (P = .023), and CD4(+)CD161(+) cells (P = .042) decreased after endotoxin...... administration. The frequency of anti-inflammatory Tregs increased (P = .033), whereas the frequency of proinflammatory CD4(+)CD161(+) cells decreased (P = .034). Endotoxemia was associated with impaired whole-blood production of tumor necrosis factor-α, interleukin-10, IL-6, IL-17, IL-2, and interferon-γ in...... response to phytohaemagglutinin but did not affect TLR4 expression on Tregs. No changes in the absolute count or frequency of BALF T cells were observed. Systemic inflammation is associated with lymphopenia, a relative increase in the frequency of anti-inflammatory Tregs, and a functional impairment of T...

  8. Operating Cell Temperature Determination in Flat-Plate Photovoltaic Modules

    International Nuclear Information System (INIS)

    Two procedures (simplified and complete) to determine me operating cell temperature in photovoltaic modules operating in real conditions assuming isothermal stationary modules are presented in this work. Some examples are included that show me dependence of this temperature on several environmental (sky, ground and ambient temperatures, solar irradiance, wind speed, etc.) and structural (module geometry and size, encapsulating materials, anti reflexive optical coatings, etc.) factors and also on electrical module performance. In a further step temperature profiles for non-isothermal modules are analysed besides transitory effects due to variable irradiance and wind gusts. (Author) 27 refs

  9. Inflammation and Cell Death in Age-Related Macular Degeneration: An Immunopathological and Ultrastructural Model.

    Science.gov (United States)

    Ardeljan, Christopher P; Ardeljan, Daniel; Abu-Asab, Mones; Chan, Chi-Chao

    2014-01-01

    The etiology of Age-related Macular Degeneration (AMD) remains elusive despite the characterization of many factors contributing to the disease in its late-stage phenotypes. AMD features an immune system in flux, as shown by changes in macrophage polarization with age, expression of cytokines and complement, microglial accumulation with age, etc. These point to an allostatic overload, possibly due to a breakdown in self vs. non-self when endogenous compounds and structures acquire the appearance of non-self over time. The result is inflammation and inflammation-mediated cell death. While it is clear that these processes ultimately result in degeneration of retinal pigment epithelium and photoreceptor, the prevalent type of cell death contributing to the various phenotypes is unknown. Both molecular studies as well as ultrastructural pathology suggest pyroptosis, and perhaps necroptosis, are the predominant mechanisms of cell death at play, with only minimal evidence for apoptosis. Herein, we attempt to reconcile those factors identified by experimental AMD models and integrate these data with pathology observed under the electron microscope-particularly observations of mitochondrial dysfunction, DNA leakage, autophagy, and cell death. PMID:25580276

  10. CD38 is expressed on inflammatory cells of the intestine and promotes intestinal inflammation.

    Science.gov (United States)

    Schneider, Michael; Schumacher, Valéa; Lischke, Timo; Lücke, Karsten; Meyer-Schwesinger, Catherine; Velden, Joachim; Koch-Nolte, Friedrich; Mittrücker, Hans-Willi

    2015-01-01

    The enzyme CD38 is expressed on a variety of hematopoietic and non-hematopoietic cells and is involved in diverse processes such as generation of calcium-mobilizing metabolites, cell activation, and chemotaxis. Here, we show that under homeostatic conditions CD38 is highly expressed on immune cells of the colon mucosa of C57BL/6 mice. Myeloid cells recruited to this tissue upon inflammation also express enhanced levels of CD38. To determine the role of CD38 in intestinal inflammation, we applied the dextran sulfate sodium (DSS) colitis model. Whereas wild-type mice developed severe colitis, CD38-/- mice had only mild disease following DSS-treatment. Histologic examination of the colon mucosa revealed pronounced inflammatory damage with dense infiltrates containing numerous granulocytes and macrophages in wild-type animals, while these findings were significantly attenuated in CD38-/- mice. Despite attenuated histological findings, the mRNA expression of inflammatory cytokines and chemokines was only marginally lower in the colons of CD38-/- mice as compared to wild-type mice. In conclusion, our results identify a function for CD38 in the control of inflammatory processes in the colon.

  11. Inflammation and Cell Death in Age-Related Macular Degeneration: An Immunopathological and Ultrastructural Model

    Directory of Open Access Journals (Sweden)

    Christopher P. Ardeljan

    2014-12-01

    Full Text Available The etiology of Age-related Macular Degeneration (AMD remains elusive despite the characterization of many factors contributing to the disease in its late-stage phenotypes. AMD features an immune system in flux, as shown by changes in macrophage polarization with age, expression of cytokines and complement, microglial accumulation with age, etc. These point to an allostatic overload, possibly due to a breakdown in self vs. non-self when endogenous compounds and structures acquire the appearance of non-self over time. The result is inflammation and inflammation-mediated cell death. While it is clear that these processes ultimately result in degeneration of retinal pigment epithelium and photoreceptor, the prevalent type of cell death contributing to the various phenotypes is unknown. Both molecular studies as well as ultrastructural pathology suggest pyroptosis, and perhaps necroptosis, are the predominant mechanisms of cell death at play, with only minimal evidence for apoptosis. Herein, we attempt to reconcile those factors identified by experimental AMD models and integrate these data with pathology observed under the electron microscope—particularly observations of mitochondrial dysfunction, DNA leakage, autophagy, and cell death.

  12. TNBS-induced inflammation modulates the function of one class of low-threshold rectal mechanoreceptors in the guinea pig.

    Science.gov (United States)

    Lynn, P A; Chen, B N; Zagorodnyuk, V P; Costa, M; Brookes, S J H

    2008-10-01

    The effects of trinitrobenzene sulfonic acid (TNBS)-induced inflammation on specialized, low-threshold, slowly adapting rectal mechanoreceptors were investigated in the guinea pig. Under isoflurane anesthesia, 300 microl saline or TNBS (15 mg/ml) in 30% ethanol was instilled 7 cm from the anal sphincter. Six or 30 days later, single unit extracellular recordings were made from rectal nerve trunks in flat-sheet in vitro preparations attached to a mechanical tissue stretcher. TNBS treatment caused macroscopic ulceration of the rectal mucosa at 6 days, which fully resolved by 30 days. Muscle contractility was unaffected by TNBS treatment. At 6 days posttreatment, responses of low-threshold rectal mechanoreceptors to circumferential stretch were increased, and the proportion of afferents responding with von Frey hair thresholds mechanoreceptor excitability in response to electrical stimulation were increased in TNBS-treated tissue, suggesting increased sensitivity of the mechanotransducer. Mechanoreceptor function at 30 days posttreatment was in most cases unchanged. The inflammatory mediator prostaglandin E(2) (1 microM) activated mechanoreceptors (6 days) in conjunction with contractile activity, but capsaicin (1 microM) failed to activate mechanoreceptors. Bradykinin (1 microM) activated mechanoreceptors independently of contractile activity and responses to stretch were increased in the presence of bradykinin. Both capsaicin and bradykinin activated unidentified stretch-insensitive afferents independently of contractile activity. Mechanoreceptor function is modulated at 6 days posttreatment but not at 30 days, suggesting a moderate increase in mechanoreceptor sensitivity in inflamed tissue but not after recovery. Other unclassified stretch-insensitive afferents are responsive to inflammatory mediators and capsaicin and may be involved in aspects of visceral sensation.

  13. Quantifying Solar Cell Cracks in Photovoltaic Modules by Electroluminescence Imaging

    DEFF Research Database (Denmark)

    Spataru, Sergiu; Hacke, Peter; Sera, Dezso;

    2015-01-01

    This article proposes a method for quantifying the percentage of partially and totally disconnected solar cell cracks by analyzing electroluminescence images of the photovoltaic module taken under high- and low-current forward bias. The method is based on the analysis of the module’s electrolumin......This article proposes a method for quantifying the percentage of partially and totally disconnected solar cell cracks by analyzing electroluminescence images of the photovoltaic module taken under high- and low-current forward bias. The method is based on the analysis of the module......’s electroluminescence intensity distribution, applied at module and cell level. These concepts are demonstrated on a crystalline silicon photovoltaic module that was subjected to several rounds of mechanical loading and humidity-freeze cycling, causing increasing levels of solar cell cracks. The proposed method can...

  14. Intensity modulated short circuit current spectroscopy for solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Kavasoglu, Nese; Sertap Kavasoglu, A.; Birgi, Ozcan; Oktik, Sener [Mugla University, Faculty of Arts and Sciences, Physics Department, TR-48000 Mugla (Turkey); Mugla University Clean Energy Research and Development Centre, TR-48000 Mugla (Turkey)

    2011-02-15

    Understanding charge separation and transport is momentously important for the rectification of solar cell performance. To probe photo-generated carrier dynamics, we implemented intensity modulated short circuit current spectroscopy (IMSCCS) on porous Si and Cu(In{sub x},Ga{sub 1-x})Se{sub 2} solar cells. In this experiment, the solar cells were lightened with sinusoidally modulated monochromatic light. The photocurrent response of the solar cell as a function of modulation frequency is measured as the optoelectronic transfer function of the system. The optoelectronic transfer function introduces the connection between the modulated light intensity and measured AC current of the solar cell. In this study, interaction of free carriers with the density of states of the porous Si and Cu(In{sub x}, Ga{sub 1-x})Se{sub 2} solar cells was studied on the basis of charge transport time by IMSCCS data. (author)

  15. An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: A nutrigenomics approach

    NARCIS (Netherlands)

    Bakker, G.C.M.; Erk, M.J. van; Pellis, L.; Wopereis, S.; Rubingh, C.M.; Cnubben, N.H.P.; Kooistra, T.; Ommen, B. van; Hendriks, H.F.J.

    2010-01-01

    Background: Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Objective: It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. Design: Dietary products

  16. Protease-activated receptor 2 activation of myeloid dendritic cells regulates allergic airway inflammation

    Directory of Open Access Journals (Sweden)

    Dienger Krista

    2011-09-01

    Full Text Available Abstract Background A common characteristic of allergens is that they contain proteases that can activate protease-activated receptor (PAR-2; however the mechanism by which PAR-2 regulates allergic airway inflammation is unclear. Methods Mice (wild type and PAR-2-deficient were sensitized using German cockroach (GC feces (frass, the isolated protease from GC frass, or through adoptive transfer of GC frass-treated bone marrow-derived dendritic cells (BMDC and measurements of airway inflammation (cellular infiltration, cytokine expression, and mucin production, serum IgE levels and airway hyperresponsiveness (AHR were assessed. BMDC were cultured, treated with GC frass and assessed for cytokine production. PAR-2 expression on pulmonary mDCs was determined by flow cytometry. Results Exposure to GC frass induced AHR and airway inflammation in wild type mice; however PAR-2-deficient mice had significantly attenuated responses. To directly investigate the role of the protease, we isolated the protease from GC frass and administered the endotoxin-free protease into the airways of mice in the presence of OVA. GC frass proteases were sufficient to promote the development of AHR, serum IgE, and Th2 cytokine production. PAR-2 expression on mDC was upregulated following GC frass exposure, but the presence of a functional PAR-2 did not alter antigen uptake. To determine if PAR-2 activation led to differential cytokine production, we cultured BMDC in the presence of GM-CSF and treated these cells ex vivo with GC frass. PAR-2-deficient BMDC released significantly less IL-6, IL-23 and TNFα compared to BMDC from wild type mice, suggesting PAR-2 activation was important in Th2/Th17 skewing cytokine production. To determine the role for PAR-2 on mDCs on the initiation of allergic airway inflammation, BMDCs from wild type and PAR-2-deficient mice were treated in the presence or absence of GC frass and then adoptively transferred into the airway of wild type mice

  17. Formation of photovoltaic modules based on polycrystalline solar cells

    OpenAIRE

    L.A. Dobrzański; A. Drygała; A. Januszka

    2009-01-01

    Purpose: The main aim of the paper is formation of photovoltaic modules and analysis of their main electric parameters.Design/methodology/approach: Photovoltaic modules were produced from four polycrystalline silicon solar cells, that were cut and next joined in series. Soft soldering technique and copper-tin strip were used for joining cells.Findings: In order to provide useful power for any application, the individual solar cells must be connected together to give the appropriate current an...

  18. IA-2 modulates dopamine secretion in PC12 cells

    OpenAIRE

    Nishimura, Takuya; Harashima, Shin-ichi; Yafang, Hu; Notkins, Abner Louis

    2009-01-01

    The secretion of the hormone insulin from beta cells is modulated by the expression of the dense core vesicle transmembrane protein IA-2. Since IA-2 is found in neuroendocrine cells throughout the body, the present experiments were initiated to determine whether the expression of IA-2 also modulates the secretion of neurotransmitters. Using the dopamine-secreting pheochromocytoma cell line PC12, we found that the overexpressions of IA-2 increased the cellular content and secretion of dopamine...

  19. Exosomes from Human Dental Pulp Stem Cells Suppress Carrageenan-Induced Acute Inflammation in Mice.

    Science.gov (United States)

    Pivoraitė, Ugnė; Jarmalavičiūtė, Akvilė; Tunaitis, Virginijus; Ramanauskaitė, Giedrė; Vaitkuvienė, Aida; Kašėta, Vytautas; Biziulevičienė, Genė; Venalis, Algirdas; Pivoriūnas, Augustas

    2015-10-01

    The primary goal of this study was to examine the effects of human dental pulp stem cell-derived exosomes on the carrageenan-induced acute inflammation in mice. Exosomes were purified by differential ultracentrifugation from the supernatants of stem cells derived from the dental pulp of human exfoliated deciduous teeth (SHEDs) cultivated in serum-free medium. At 1 h post-carrageenan injection, exosomes derived from supernatants of 2 × 10(6) SHEDs were administered by intraplantar injection to BALB/c mice; 30 mg/kg of prednisolone and phosphate-buffered saline (PBS) were used as positive and negative controls, respectively. Edema was measured at 6, 24, and 48 h after carrageenan injection. For the in vivo imaging experiments, AngioSPARK750, Cat B 750 FAST, and MMPSense 750 FAST were administered into the mouse tail vein 2 h post-carrageenan injection. Fluorescence images were acquired at 6, 24, and 48 h after edema induction by IVIS Spectrum in vivo imaging system. Exosomes significantly reduced the carrageenan-induced edema at all the time points studied (by 39.5, 41.6, and 25.6% at 6, 24, and 48 h after injection, respectively), to similar levels seen with the positive control (prednisolone). In vivo imaging experiments revealed that, both exosomes and prednisolone suppress activities of cathepsin B and matrix metalloproteinases (MMPs) at the site of carrageenan-induced acute inflammation, showing more prominent effects of prednisolone at the early stages, while exosomes exerted their suppressive effects gradually and at later time points. Our study demonstrates for the first time that exosomes derived from human dental pulp stem cells suppress carrageenan-induced acute inflammation in mice.

  20. Heme in intestinal epithelial cell turnover, differentiation,detoxification, inflammation, carcinogenesis, absorption and motility

    Institute of Scientific and Technical Information of China (English)

    Phillip S Oates; Adrian R West

    2006-01-01

    The gastrointestinal tract is lined by a simple epithelium that undergoes constant renewal involving cell division,differentiation and cell death. In addition, the epithelial lining separates the hostile processes of digestion and absorption that occur in the intestinal lumen from the aseptic environment of the internal milieu by defensive mechanisms that protect the epithelium from being breached. Central to these defensive processes is the synthesis of heme and its catabolism by heme oxygenase (HO). Dietary heme is also an important source of iron for the body which is taken up intact by the enterocyte.This review describes the recent literature on the diverse properties of heme/HO in the intestine tract.The roles of heme/HO in the regulation of the cell cycle/apoptosis, detoxification of xenobiotics, oxidative stress,inflammation, development of colon cancer, hemeiron absorption and intestinal motility are specifically examined.

  1. Temperature dependence of photovoltaic cells, modules, and systems

    Energy Technology Data Exchange (ETDEWEB)

    Emery, K.; Burdick, J.; Caiyem, Y. [National Renewable Energy Lab., Golden, CO (United States)] [and others

    1996-05-01

    Photovoltaic (PV) cells and modules are often rated in terms of a set of standard reporting conditions defined by a temperature, spectral irradiance, and total irradiance. Because PV devices operates over a wide range of temperatures and irradiances, the temperature and irradiance related behavior must be known. This paper surveys the temperature dependence of crystalline and thin-film, state-of-the-art, research-size cells, modules, and systems measured by a variety of methods. The various error sources and measurement methods that contribute to cause differences in the temperature coefficient for a given cell or module measured with various methods are discussed.

  2. Gene Expression Profiling Identifies Cell Proliferation and Inflammation as the Predominant Pathways Regulated by Aryl Hydrocarbon Receptor in Primary Human Fetal Lung Cells Exposed to Hyperoxia.

    Science.gov (United States)

    Shivanna, Binoy; Maity, Suman; Zhang, Shaojie; Patel, Ananddeep; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E; Belmont, John; Coarfa, Cristian; Moorthy, Bhagavatula

    2016-07-01

    Exposure to hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. We observed that aryl hydrocarbon receptor (AhR) signaling protects newborn mice and primary fetal human pulmonary microvascular endothelial cells (HPMECs) against hyperoxic injury. Additionally, a recent genome-wide transcriptome study in a newborn mouse model of BPD identified AhR as a key regulator of hyperoxia-induced gene dysregulation. Whether the AhR similarly deregulates genes in HPMEC is unknown. Therefore, the objective of this study was to characterize transcriptome level gene expression profile in AhR-sufficient and -deficient HPMEC exposed to normoxic and hyperoxic conditions. Global gene expression profiling was performed using Illumina microarray platform and selected genes were validated by real-time RT-PCR. AhR gene expression and hyperoxia independently affected the expression of 540 and 593 genes, respectively. Two-way ANOVA further identified 85 genes that were affected by an interaction between AhR expression and exposure to hyperoxia. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology, and Reactome pathway analysis identified cell proliferation, immune function, cytokine signaling, and organ development as the major pathways affected in AhR-deficient cells. The biological processes that were significantly enriched by hyperoxia included metabolic process, stress response, signal transduction, cell cycle, and immune regulation. Cell cycle was the predominant pathway affected by the combined effect of AhR knockdown and hyperoxia. Functional analysis of cell cycle showed that AhR-deficient cells had decreased proliferation compared with AhR-sufficient cells. These findings suggest that AhR modulates hyperoxic lung injury by regulating the genes that are necessary for cell proliferation and inflammation. PMID:27103661

  3. Wedelolactone inhibits LPS-induced pro-inflammation via NF-kappaB Pathway in RAW 264.7 cells

    OpenAIRE

    Yuan, Fang; Chen, Jie; Sun, Ping-Ping; Guan, Su; Xu, Jing

    2013-01-01

    Background Wedelolactone (WEL), a major coumestan ingredient in Wedelia chinensis, has been used to treat septic shock, hepatitis and venom poisoning in traditional Chinese medicines. The objective of the study was to elucidate the anti-inflammatory effects and mechanism of WEL with a cellular model of lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results To study the role of WEL in pro-inflammation, we measured key inflammation mediators and end products including nitric oxide (NO), pros...

  4. Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells.

    Science.gov (United States)

    Barbosa, João P; Neves, Ana R; Silva, Andreia M; Barbosa, Mário A; Reis, M Salette; Santos, Susana G

    2016-01-01

    to promote a similar effect. Taken together, the results presented show that NLC are suitable carriers of fluorescent labels or bioactive molecules for human DCs, leading to inflammation modulation. PMID:27555771

  5. The impact of inflammation and immune activation on B cell differentiation during HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Nicolas eRuffin

    2012-01-01

    Full Text Available HIV-1 infection is characterized by continuous antigenic stimulation, chronic immune activation and impaired survival of T and B cells. A decline of resting memory B cells has previously been reported to occur in both children and adults infected with HIV-1; these cells are responsible for mounting and maintaining an adequate serological response to antigens previously encountered in life through natural infection or vaccination. Further understanding of the mechanisms leading to impaired B cell differentiation and germinal center reaction might be essential to design new HIV vaccines and therapies that could improve humoral immune responses in HIV-1 infected individuals. In the present article we summarize the literature and present our view on critical mechanisms of B cell development which are impaired during HIV-1 infection. We also discuss the impact of microbial translocation, a driving force for persistent inflammation during HIV-1 infection, on survival of terminally differentiated B cells and how the altered expression of cytokines/chemokines pivotal for communication between T and B cells in lymphoid tissues may impair formation of memory B cells.

  6. Anti-coreceptor therapy drives selective T cell egress by suppressing inflammation-dependent chemotactic cues

    Science.gov (United States)

    Martin, Aaron J.; Clark, Matthew; Gojanovich, Gregory; Manzoor, Fatima; Miller, Keith; Kline, Douglas E.; Morillon, Y. Maurice; Wang, Bo

    2016-01-01

    There continues to be a need for immunotherapies to treat type 1 diabetes in the clinic. We previously reported that nondepleting anti-CD4 and -CD8 Ab treatment effectively reverses diabetes in new-onset NOD mice. A key feature of the induction of remission is the egress of the majority of islet-resident T cells. How this occurs is undefined. Herein, the effects of coreceptor therapy on islet T cell retention were investigated. Bivalent Ab binding to CD4 and CD8 blocked TCR signaling and T cell cytokine production, while indirectly downregulating islet chemokine expression. These processes were required for T cell retention, as ectopic IFN-γ or CXCL10 inhibited Ab-mediated T cell purging. Importantly, treatment of humanized mice with nondepleting anti–human CD4 and CD8 Ab similarly reduced tissue-infiltrating human CD4+ and CD8+ T cells. These findings demonstrate that Ab binding of CD4 and CD8 interrupts a feed-forward circuit by suppressing T cell–produced cytokines needed for expression of chemotactic cues, leading to rapid T cell egress from the islets. Coreceptor therapy therefore offers a robust approach to suppress T cell–mediated pathology by purging T cells in an inflammation-dependent manner.

  7. Deoxynivalenol induced mouse skin cell proliferation and inflammation via MAPK pathway

    International Nuclear Information System (INIS)

    Several toxicological manifestations of deoxynivalenol (DON), a mycotoxin, are well documented; however, dermal toxicity is not yet explored. The effect of topical application of DON to mice was studied using markers of skin proliferation, inflammation and tumor promotion. Single topical application of DON (84–672 nmol/mouse) significantly enhanced dermal hyperplasia and skin edema. DON (336 and 672 nmol) caused significant enhancement in [3H]-thymidine uptake in DNA along with increased myeloperoxidase and ornithine decarboxylase activities, suggesting tissue inflammation and cell proliferation. Furthermore, DON (168 nmol) caused enhanced expression of RAS, and phosphorylation of PI3K/Akt, ERK, JNK and p38 MAPKs. DON exposure also showed activation of transcription factors, c-fos, c-jun and NF-κB along with phosphorylation of IkBα. Enhanced phosphorylation of NF-κB by DON caused over expression of target proteins, COX-2, cyclin D1 and iNOS in skin. Though a single topical application of DMBA followed by twice weekly application of DON (84 and 168 nmol) showed no tumorigenesis after 24 weeks, however, histopathological studies suggested hyperplasia of the epidermis and hypertrophy of hair follicles. Interestingly, intestine was also found to be affected as enlarged Peyer's patches were observed, suggesting inflammatory effects which were supported by elevation of inflammatory cytokines after 24 weeks of topical application of DON. These results suggest that DON induced cell proliferation in mouse skin is through the activation of MAPK signaling pathway involving transcription factors NFκB and AP-1, further leading to transcriptional activation of downstream target proteins c-fos, c-jun, cyclin D1, iNOS and COX-2 which might be responsible for its inflammatory potential. - Highlights: • Topical application of DON enhanced epidermal inflammation and cell proliferation. • DON follows PI3K/Akt/MAPK signaling cascade, with activation of AP-1 and NF-κB.

  8. Deoxynivalenol induced mouse skin cell proliferation and inflammation via MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Sakshi [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Department of Biochemistry, Banaras Hindu University (BHU), Varanasi (India); Tripathi, Anurag [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Chaudhari, Bhushan P. [Pathology Laboratory, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, PO Box 80, Lucknow 226001, Uttar Pradesh (India); Dwivedi, Premendra D. [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Pandey, Haushila P. [Department of Biochemistry, Banaras Hindu University (BHU), Varanasi (India); Das, Mukul, E-mail: mditrc@rediffmail.com [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India)

    2014-09-01

    Several toxicological manifestations of deoxynivalenol (DON), a mycotoxin, are well documented; however, dermal toxicity is not yet explored. The effect of topical application of DON to mice was studied using markers of skin proliferation, inflammation and tumor promotion. Single topical application of DON (84–672 nmol/mouse) significantly enhanced dermal hyperplasia and skin edema. DON (336 and 672 nmol) caused significant enhancement in [{sup 3}H]-thymidine uptake in DNA along with increased myeloperoxidase and ornithine decarboxylase activities, suggesting tissue inflammation and cell proliferation. Furthermore, DON (168 nmol) caused enhanced expression of RAS, and phosphorylation of PI3K/Akt, ERK, JNK and p38 MAPKs. DON exposure also showed activation of transcription factors, c-fos, c-jun and NF-κB along with phosphorylation of IkBα. Enhanced phosphorylation of NF-κB by DON caused over expression of target proteins, COX-2, cyclin D1 and iNOS in skin. Though a single topical application of DMBA followed by twice weekly application of DON (84 and 168 nmol) showed no tumorigenesis after 24 weeks, however, histopathological studies suggested hyperplasia of the epidermis and hypertrophy of hair follicles. Interestingly, intestine was also found to be affected as enlarged Peyer's patches were observed, suggesting inflammatory effects which were supported by elevation of inflammatory cytokines after 24 weeks of topical application of DON. These results suggest that DON induced cell proliferation in mouse skin is through the activation of MAPK signaling pathway involving transcription factors NFκB and AP-1, further leading to transcriptional activation of downstream target proteins c-fos, c-jun, cyclin D1, iNOS and COX-2 which might be responsible for its inflammatory potential. - Highlights: • Topical application of DON enhanced epidermal inflammation and cell proliferation. • DON follows PI3K/Akt/MAPK signaling cascade, with activation of AP-1 and NF

  9. Regulation of lovastatin on a key inflammation-related microRNA in myocardial cells

    Institute of Scientific and Technical Information of China (English)

    Guo Weizao; Liu Huichen; Li Lin; Yang Man; Du Aihua

    2014-01-01

    Background Advances in the understanding of cardiovascular pathogenesis have highlighted that inflammation plays a central role in athemsclemtic coronary heart disease.Therefore,exploring pharmacologically based anti-inflammatory treatments to be used in cardiovascular therapeutics is worthwhile to promote the discovery of novel ways of treating cardiovascular disorders.Methods The myocardial cell line H9c2(2-1) was exposed to lipopolysacchadde (LPS) in culture and resulted in a cellular pro-inflammation status,miR-21 microRNA levels were detected using quantitative real-time polymerase chain reaction (Q-RT-PCR).The influence of Iovastatin on miR-21 under normal and pro-inflammatory conditions was tested after being added to the cell culture mixture for 24 hours.Conditional gene function of two predicted cardiovascular system relevant downstream targets of miR-21,protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and signal transducer and activator of transcription 3 (STAT3),were analyzed with immunoblotting.Results Forty-eight hours of LPS treatment significantly increased the miR-21 to 170.71%±34.32% of control levels (P=0.002).Co-treatment with Iovastatin for 24 hours before harvesting attenuated the up-regulation of miR-21 (P=0.013).Twenty-four hours of Iovastatin exposure up-regulated PPP1R3A to 143.85%±21.89% of control levels in cardiomyocytes (P=0.023).Lovastatin up-regulated the phosphorylation level of STAT3 compared to the background LPS pretreatment (P=0.0077),this effect was significantly (P=0.018) blunted when miR-21 was functionally inhibited.Conclusions miR-21 plays a major role in the regulation of the cellular anti-inflammation effects of Iovastatin.

  10. Molecular Basis Linking Platelet to Inflammation

    Institute of Scientific and Technical Information of China (English)

    马丽萍

    2010-01-01

    @@ Introduction Blood platelets not only play an important role in hemostasis and thrombosis,but increasing evidence show that they participate in the induction of inflammation.Firstly,platelets contain and release cytokines and immune mediators.And platelets are able to modulate and regulate the function of surrounding cells by adhesion molecules or by the release of various factors.

  11. Potential of thin-film solar cell module technology

    Science.gov (United States)

    Shimada, K.; Ferber, R. R.; Costogue, E. N.

    1985-01-01

    During the past five years, thin-film cell technology has made remarkable progress as a potential alternative to crystalline silicon cell technology. The efficiency of a single-junction thin-film cell, which is the most promising for use in flat-plate modules, is now in the range of 11 percent with 1-sq cm cells consisting of amorphous silicon, CuInSe2 or CdTe materials. Cell efficiencies higher than 18 percent, suitable for 15 percent-efficient flat plate modules, would require a multijunction configuration such as the CdTe/CuInSe2 and tandem amorphous-silicon (a-Si) alloy cells. Assessments are presented of the technology status of thin-film-cell module research and the potential of achieving the higher efficiencies required for large-scale penetration into the photovoltaic (PV) energy market.

  12. Colonic inflammation in mice is improved by cigarette smoke through iNKT cells recruitment.

    Directory of Open Access Journals (Sweden)

    Muriel Montbarbon

    Full Text Available Cigarette smoke (CS protects against intestinal inflammation during ulcerative colitis. Immunoregulatory mechanisms sustaining this effect remain unknown. The aim of this study was to assess the effects of CS on experimental colitis and to characterize the intestinal inflammatory response at the cellular and molecular levels. Using the InExpose® System, a smoking device accurately reproducing human smoking habit, we pre-exposed C57BL/6 mice for 2 weeks to CS, and then we induced colitis by administration of dextran sodium sulfate (DSS. This system allowed us to demonstrate that CS exposure improved colonic inflammation (significant decrease in clinical score, body weight loss and weight/length colonic ratio. This improvement was associated with a significant decrease in colonic proinflammatory Th1/Th17 cytokine expression, as compared to unexposed mice (TNF (p=0.0169, IFNγ (p<0.0001, and IL-17 (p=0.0008. Smoke exposure also induced an increased expression of IL-10 mRNA (p=0.0035 and a marked recruitment of iNKT (invariant Natural Killer T; CD45+ TCRβ+ CD1d tetramer+ cells in the colon of DSS-untreated mice. Demonstration of the role of iNKT cells in CS-dependent colitis improvement was performed using two different strains of NKT cells deficient mice. Indeed, in Jα18KO and CD1dKO animals, CS exposure failed to induce significant regulation of DSS-induced colitis both at the clinical and molecular levels. Thus, our study demonstrates that iNKT cells are pivotal actors in the CS-dependent protection of the colon. These results highlight the role of intestinal iNKT lymphocytes and their responsiveness to environmental stimuli. Targeting iNKT cells would represent a new therapeutic way for inflammatory bowel diseases.

  13. Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation.

    Science.gov (United States)

    Izcue, Ana; Coombes, Janine L; Powrie, Fiona

    2006-08-01

    The gastrointestinal (GI) tract is the main interface where the body encounters exogenous antigens. It is crucial that the local response here is tightly regulated to avoid an immune reaction against dietary antigens and commensal flora while still mounting an efficient defense against pathogens. Faults in establishing intestinal tolerance can lead to disease, inducing local and often also systemic inflammation. Studies in human as well as in animal models suggest a role for regulatory T cells (Tregs) in maintaining intestinal homeostasis. Transfer of Tregs can not only prevent the development of colitis in animal models but also cure established disease, acting both systemically and at the site of inflammation. In this review, we discuss the major regulatory pathways, including transforming growth factor-beta (TGF-beta), interleukin-10 (IL-10), and cytotoxic T-lymphocyte antigen-4 (CTLA-4), and their role in Treg-mediated control of systemic and mucosal responses. In addition, we give an overview of the known mechanisms of lymphocyte migration to the intestine and discuss how CD103 expression can influence the balance between regulatory and effector T cells. Further understanding of the factors that control the activity of Tregs in different immune compartments may facilitate the design of strategies to target regulation in a tissue-specific way. PMID:16903919

  14. Transient Receptor Potential Ankyrin 1 Channel Localized to Non-Neuronal Airway Cells Promotes Non-Neurogenic Inflammation

    DEFF Research Database (Denmark)

    Nassini, Romina; Pedretti, Pamela; Moretto, Nadia;

    2012-01-01

    inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express...... functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells...... (BAL) fluid of wild-type mice. This effect of TRPA1 agonists was attenuated by TRPA1 antagonism or in TRPA1-deficient mice, but not by pharmacological ablation of sensory nerves.Our results demonstrate that, although either TRPV1 or TRPA1 activation causes airway neurogenic inflammation, solely TRPA1...

  15. MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development.

    Science.gov (United States)

    O'Connell, Ryan M; Kahn, Daniel; Gibson, William S J; Round, June L; Scholz, Rebecca L; Chaudhuri, Aadel A; Kahn, Melissa E; Rao, Dinesh S; Baltimore, David

    2010-10-29

    Mammalian noncoding microRNAs (miRNAs) are a class of gene regulators that have been linked to immune system function. Here, we have investigated the role of miR-155 during an autoimmune inflammatory disease. Consistent with a positive role for miR-155 in mediating inflammatory responses, Mir155(-/-) mice were highly resistant to experimental autoimmune encephalomyelitis (EAE). miR-155 functions in the hematopoietic compartment to promote the development of inflammatory T cells including the T helper 17 (Th17) cell and Th1 cell subsets. Furthermore, the major contribution of miR-155 to EAE was CD4(+) T cell intrinsic, whereas miR-155 was also required for optimum dendritic cell production of cytokines that promoted Th17 cell formation. Our study shows that one aspect of miR-155 function is the promotion of T cell-dependent tissue inflammation, suggesting that miR-155 might be a promising therapeutic target for the treatment of autoimmune disorders. PMID:20888269

  16. Inhibitors of inflammation and endogenous surfactant pool size as modulators of lung injury with initiation of ventilation in preterm sheep

    OpenAIRE

    Polglase Graeme R; Nitsos Ilias; Pillow J Jane; Kallapur Suhas G; Hillman Noah H; Ikegami Machiko; Jobe Alan H

    2010-01-01

    Abstract Background Increased pro-inflammatory cytokines in tracheal aspirates correlate with the development of BPD in preterm infants. Ventilation of preterm lambs increases pro-inflammatory cytokines and causes lung inflammation. Objective We tested the hypothesis that selective inhibitors of pro-inflammatory signaling would decrease lung inflammation induced by ventilation in preterm newborn lambs. We also examined if the variability in injury response was explained by variations in the e...

  17. Busulfan and cyclosphamide induce liver inflammation through NLRP3 activation in mice after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Qiao, Jianlin; Huang, Yujin; Xia, Yuan; Chu, Peipei; Yao, Haina; Xu, Linyan; Qi, Kunming; Liu, Yun; Xu, Kailin; Zeng, Lingyu

    2015-12-04

    The aim of this study was to evaluate the role of NLRP3 inflammasome on BU/CY-induced liver inflammation in mice after HSCT. HSCT mice model was established through infusion of 5 × 10(6) bone marrow mononuclear cells after conditioned with BU/CY. On day 7, 14, 21 and 28 after HSCT, mice were sacrificed for analysis of liver inflammation, cytokine secretion, NLRP3 expression and caspase-1 activation as well as release of ATP and high-mobility group protein B1 (HMGB1). Furthermore, NLRP3 selective inhibitor (BAY 11-7082) was administrated into mice after HSCT to evaluate its effects on liver inflammation. Severe liver inflammation and damage with elevated secretion of IL-1β and IL-18 were found in mice after HSCT. Meanwhile, elevated expressions of NLRP3 and caspase-1 activation in liver were found. In addition, increased release of ATP and HMGB1 were observed. Selective inhibition of NLRP3 decreased caspase-1 activation and secretion of IL-1β and IL-18. Furthermore, NLRP3 inhibition also reduced infiltration of macrophages and neutrophils and improved liver function. In conclusion, NLRP3 was involved in BU/CY-induced liver inflammation after HSCT and selectively inhibited it ameliorated liver inflammation and improved liver function, suggesting targeting NLRP3 might be a new approach in the prophylaxis of liver inflammation after HSCT.

  18. Modulation of mast cell and basophil functions by benzene metabolites.

    Science.gov (United States)

    Triggiani, Massimo; Loffredo, Stefania; Granata, Francescopaolo; Staiano, Rosaria I; Marone, Gianni

    2011-11-01

    Benzene is a carcinogenic compound used in industrial manufacturing and a common environmental pollutant mostly derived from vehicle emissions and cigarette smoke. Benzene exposure is associated with a variety of clinical conditions ranging from hematologic diseases to chronic lung disorders. Beside its direct toxicity, benzene exerts multiple effects after being converted to reactive metabolites such as hydroquinone and benzoquinone. Mast cells and basophils are primary effector cells involved in the development of respiratory allergies such as rhinitis and bronchial asthma and they play an important role in innate immunity. Benzene and its metabolites can influence mast cell and basophil responses either directly or by interfering with other cells, such as T cells, macrophages and monocytes, which are functionally connected to mast cells and basophils. Hydroquinone and benzoquinone inhibit the release of preformed mediators, leukotriene synthesis and cytokine production in human basophils stimulated by IgE- and non IgE-mediated agonists. Furthermore, these metabolites reduce IgE-mediated degranulation of mast cells and the development of allergic lung inflammation in rats. Both in vitro and in vivo studies indicate that benzene metabolites alter biochemical and functional activities of other immunocompetent cells and may impair immune responses in the lung. These inhibitory effects of benzene metabolites are primarily mediated by interference with early transduction signals such as PI3 kinase. Together, currently available studies indicate that benzene metabolites interfere by multiple mechanisms with the role of basophils and mast cells in innate immunity and in chronic inflammation in the lung. PMID:22103854

  19. Mast cells are key mediators of cathelicidin-initiated skin inflammation in rosacea.

    Science.gov (United States)

    Muto, Yumiko; Wang, Zhenping; Vanderberghe, Matthieu; Two, Aimee; Gallo, Richard L; Di Nardo, Anna

    2014-11-01

    Rosacea is a chronic inflammatory skin disease whose pathophysiological mechanism is still unclear. However, it is known that mast cell (MC) numbers are increased in the dermis of rosacea patients. MC proteases not only recruit other immune cells, which amplify the inflammatory response, but also cause vasodilation and angiogenesis. MCs are also one of the primary sources of cathelicidin LL-37 (Cath LL-37), an antimicrobial peptide that has been shown to be an enabler of rosacea pathogenesis. Here, we demonstrate that MCs are key mediators of cathelicidin-initiated skin inflammation. After Cath LL-37 injection into the dermis, MC-deficient B6.Cg-Kit(W-sh)/HNihrJaeBsmJ (KitW-sh) mice did not develop rosacea-like features. Conversely, chymase (Prosacea subjects who showed a decrease in matrix metalloproteinase activity (Prosacea treatment.

  20. Type 2 Innate Lymphoid Cells: Friends or Foes—Role in Airway Allergic Inflammation and Asthma

    Directory of Open Access Journals (Sweden)

    Abbas Pishdadian

    2012-01-01

    Full Text Available Innate-like lymphocytes (ILLs and innate lymphoid cells (ILCs are two newly characterized families of lymphocytes with limited and no rearranged antigen receptors, respectively. These soldiers provide a first line of defense against foreign insults by triggering a prompt innate immune response and bridging the gap of innate and adaptive immunity. Type 2 innate lymphoid cells (ILCs2 are newly identified members of the ILC family that play a key role in type 2 immune responses by prompt production of type 2 cytokines (especially IL-5 and IL-13 in response to antigen-induced IL-25/33 and by recruiting type 2 “immune franchise.” Regarding the two different roles of type 2 cytokines, helminth expulsion and type 2-related diseases, here we review the latest advances in ILC2 biology and examine the pivotal role of resident ILCs2 in allergen-specific airway inflammation and asthma.

  1. Endothelial cell activation, oxidative stress and inflammation induced by a panel of metal-based nanomaterials

    DEFF Research Database (Denmark)

    Danielsen, Pernille Høgh; Cao, Yi; Roursgaard, Martin;

    2015-01-01

    in the development of cardiovascular diseases. The NMs used were five TiO2 NMs with different charge, size and crystal structure, coated and uncoated ZnO NMs and Ag which were tested in a wide concentration range. There were major differences between the types of NMs; exposure to ZnO and Ag resulted in cytotoxicity...... expression. The toxicological profile of cardiovascular disease-relevant biomarkers depended on composition, size and crystal structure of TiO2 NMs, whereas the charge on TiO2 NMs and the coating of ZnO NMs were not associated with differences in toxicological profile.......The importance of composition, size, crystal structure, charge and coating of metal-based nanomaterials (NMs) were evaluated in human umbilical vein endothelial cells (HUVECs) and/or THP-1 monocytic cells. Biomarkers of oxidative stress and inflammation were assessed because they are important...

  2. Comparison of lung alveolar and tissue cells in silica-induced inflammation.

    Science.gov (United States)

    Sjöstrand, M; Absher, P M; Hemenway, D R; Trombley, L; Baldor, L C

    1991-01-01

    The silicon dioxide mineral, cristobalite (CRS) induces inflammation involving both alveolar cells and connective tissue compartments. In this study, we compared lung cells recovered by whole lung lavage and by digestion of lung tissue from rats at varying times after 8 days of exposure to aerosolized CRS. Control and exposed rats were examined between 2 and 36 wk after exposure. Lavaged cells were obtained by bronchoalveolar lavage with phosphate-buffered saline. Lung wall cells were prepared via collagenase digestion of lung tissue slices. Cells from lavage and lung wall were separated by Percoll density centrifugation. The three upper fractions, containing mostly macrophages, were cultured, and the conditioned medium was assayed for effect on lung fibroblast growth and for activity of the lysosomal enzyme, N-acetyl-beta-D-glucosaminidase. Results demonstrated that the cells separated from the lung walls exhibited different reaction patterns compared with those cells recovered by lavage. The lung wall cells exhibited a progressive increase in the number of macrophages and lymphocytes compared with a steady state in cells of the lung lavage. This increase in macrophages apparently was due to low density cells, which showed features of silica exposure. Secretion of a fibroblast-stimulating factor was consistently high by lung wall macrophages, whereas lung lavage macrophages showed inconsistent variations. The secretion of NAG was increased in lung lavage macrophages, but decreased at most observation times in lung wall macrophages. No differences were found among cells in the different density fractions regarding fibroblast stimulation and enzyme secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Airway responsiveness to mannitol in asthma is associated with chymase-positive mast cells and eosinophilic airway inflammation

    DEFF Research Database (Denmark)

    Sverrild, Asger; Bergqvist, Anders; Baines, Katherine J;

    2016-01-01

    BACKGROUND: Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway...... tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell-associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol. METHODS: Airway hyperresponsiveness to inhaled mannitol was measured in 23 non......-smoking, corticosteroid-free asthmatic individuals and 10 healthy controls. Mast cells and eosinophils were identified in mucosal biopsies from all participants. Mast cells were divided into phenotypes based on the presence of chymase. mRNA expression of mast cell-associated genes was measured by real-time PCR. RESULTS...

  4. Mesenteric lymph nodes contribute to proinflammatory Th17-cell generation during inflammation of the small intestine in mice.

    Science.gov (United States)

    Kawabe, Takeshi; Suzuki, Nobu; Yamaki, Satoshi; Sun, Shu-Lan; Asao, Atsuko; Okuyama, Yuko; So, Takanori; Iwakura, Yoichiro; Ishii, Naoto

    2016-05-01

    cells of the small intestine, including Th17 cells, are critically involved in host protection from microbial infection, and also contribute to the pathogenesis of small bowel inflammatory disorders. Accumulating evidence suggests that mesenteric lymph nodes (MLNs) play important roles in gut-tropic T-cell generation, although it is still unclear if MLNs are involved in the pathogenesis of small intestine inflammation. To address this issue, we analyzed the roles of both MLNs and Peyer's patches (PPs) by evaluating MLN- or PP-deficient mice in an experimental model of small intestine inflammation, induced by CD3-specific mAb injection. Interestingly, MLNs, but not PPs, were essential for the pathogenesis of intestinal inflammation, in particular the accumulation and infiltration of CD4(+) T-cell populations, including Th17 cells, from the blood. In addition, CD4(+) T-cell accumulation was dependent on the function of the α4 β7 integrin. Furthermore, MLN removal led to a significantly reduced number of peripheral α4 β7 (+) CD4(+) effector memory T cells under normal conditions, suggesting that MLNs may play a role in maintaining the number of gut-tropic CD4(+) effector memory T cells circulating in the blood. Taken together, the present study highlights the important role of MLNs in contributing to the pathogenesis of small intestine inflammation.

  5. Chemistry and biology of the compounds that modulate cell migration.

    Science.gov (United States)

    Tashiro, Etsu; Imoto, Masaya

    2016-03-01

    Cell migration is a fundamental step for embryonic development, wound repair, immune responses, and tumor cell invasion and metastasis. Extensive studies have attempted to reveal the molecular mechanisms behind cell migration; however, they remain largely unclear. Bioactive compounds that modulate cell migration show promise as not only extremely powerful tools for studying the mechanisms behind cell migration but also as drug seeds for chemotherapy against tumor metastasis. Therefore, we have screened cell migration inhibitors and analyzed their mechanisms for the inhibition of cell migration. In this mini-review, we introduce our chemical and biological studies of three cell migration inhibitors: moverastin, UTKO1, and BU-4664L.

  6. Vitamin D Attenuates Kidney Fibrosis via Reducing Fibroblast Expansion, Inflammation, and Epithelial Cell Apoptosis.

    Science.gov (United States)

    Arfian, Nur; Muflikhah, Khusnul; Soeyono, Sri Kadarsih; Sari, Dwi Cahyani Ratna; Tranggono, Untung; Anggorowati, Nungki; Romi, Muhammad Mansyur

    2016-01-01

    Kidney fibrosis is the common final pathway of chronic kidney diseases (CKD). It is characterized by myofibroblast formation, inflammation, and epithelial architecture damage. Vitamin D is known as a renoprotective agent, although the precise mechanism is not well understood. This study aimed to elucidate the effect of vitamin D in fibroblast expansion, inflammation, and apoptosis in kidney fibrosis. We performed unilateral ureteral obstruction (UUO) in male Swiss-Webster background mice (3 months, 30-40 grams) to induce kidney fibrosis. The mice (n=25) were divided into five groups: UUO, 3 groups treated with different oral vitamin D doses (0.125 µg/kg (UUO+VD1), 0.25 µg/kg (UUO+VD2), and 0.5 µg/kg (UUO+VD3), and a Sham operation (SO) group with ethanol 0.2% supplementation. We sacrificed the mice on day14 after the operation and harvested the kidney. We made paraffin sections for histological analysis. Tubular injury and fibrosis were quantified based on periodic acid-Schiff (PAS) and Sirius Red (SR) staining. Immunostaining was done for examination of myofibroblasts (αSMA), fibroblasts (PDGFRβ), TLR4, and apoptosis (TUNEL). We did RNA extraction and cDNA for Reverse transcriptase PCR (RT-PCR) experiment for measuring MCP-1, ICAM-1, TLR4, and collagen 1 expression. TGFβ1 level was quantified using ELISA. We observed a significantly lower levels of fibrosis (pexpression of collagen1, as well as inflammation-mediator expression (MCP-1, ICAM-1, TLR4) in the UUO+VD-1 group compared with the SO group. Vitamin D reduces kidney fibrosis through inhibition of fibroblast activation, and ameliorates epithelial cell architecture. PMID:27578035

  7. DNA repair and cell cycle biomarkers of radiation exposure and inflammation stress in human blood.

    Directory of Open Access Journals (Sweden)

    Helen Budworth

    Full Text Available DNA damage and repair are hallmarks of cellular responses to ionizing radiation. We hypothesized that monitoring the expression of DNA repair-associated genes would enhance the detection of individuals exposed to radiation versus other forms of physiological stress. We employed the human blood ex vivo radiation model to investigate the expression responses of DNA repair genes in repeated blood samples from healthy, non-smoking men and women exposed to 2 Gy of X-rays in the context of inflammation stress mimicked by the bacterial endotoxin lipopolysaccharide (LPS. Radiation exposure significantly modulated the transcript expression of 12 genes of 40 tested (2.2E-06inflammation alone, or combined exposures. Our findings suggest that DNA repair gene expression may be helpful to identify biodosimeters of exposure to radiation, especially within high-complexity exposure scenarios.

  8. Formation of photovoltaic modules based on polycrystalline solar cells

    Directory of Open Access Journals (Sweden)

    L. A. Dobrzański

    2009-12-01

    Full Text Available Purpose: The main aim of the paper is formation of photovoltaic modules and analysis of their main electric parameters.Design/methodology/approach: Photovoltaic modules were produced from four polycrystalline silicon solar cells, that were cut and next joined in series. Soft soldering technique and copper-tin strip were used for joining cells.Findings: In order to provide useful power for any application, the individual solar cells must be connected together to give the appropriate current and voltage levels. Taking this fact into account the analysis of photovoltaic module construction was performed.Research limitations/implications: The main goal of the research is to show the practical application of solar cells. Two photovoltaic modules were assembled and their basic electric properties were analysed. It was shown that they may be successively applied as an alternative energy source.Practical implications: Photovoltaic modules are irreplaceable in areas which are far away from power network. Simply photovoltaic module can supply small device without any problem.Originality/value: The produced photovoltaic modules and photovoltaic systems confirm the utility of solar energy in every place where the sun radiation is available. Because of exhaust conventional energy sources like coal or earth gas, new renewable sources of energy (sunlight, wind are more and more often used. It brings huge ecological benefits.

  9. Anti-nociceptive role of neuropeptide Y in the nucleus accumbens in rats with inflammation, an effect modulated by mu- and kappa-opioid receptors

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Recent study in our laboratory showed that neuropeptide Y (NPY) plays an antinociceptive role in the nucleus accumbens (NAc) in intact rats. The present study was performed to further investigate the effect of NPY in nociceptive modulation in the NAc of rats with inflammation, and the possible interaction between NPY and the opioid systems. Experimental inflammation was induced by subcutaneous injection of carrageenan into the left hindpaw of rats. Intra-NAc administration of NPY induced a dose-dependent increase of hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulations in rats with inflammation. The anti-nociceptive effect of NPY was significantly blocked by subsequent intra-NAc injection of the Y1 receptor antagonist NPY28-36, suggesting an involvement of Y1 receptor in the NPY-induced anti-nociception. Furthermore, intra-NAc administration of the opioid antagonist naloxone significantly antagonized the increased HWLs induced by preceding intra-NAc injection of NPY, suggesting an involvement of the endogenous opioid system in the NPY-induced anti-nociception in the NAc during inflammation. Moreover, the NPY-induced anti-nociception was attenuated by following intra-NAc injection of the μ-opioid antagonist β-funaltrexamine (β-FNA), and κ-opioid antagonist nor-binaltorphimine (norBNI), but not by δ-opioid antagonist naltrindole, indicating that μ- and κ-opioid receptors, not δ-opioid receptor, are involved in the NPY-induced anti-nociception in the NAc in rats with inflammation.

  10. Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

    Science.gov (United States)

    Chao, Yi-Ning; Sun, David; Peng, Yen-Chun; Wu, Yuh-Lin

    2016-01-01

    Cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) are two important inflammatory mediators in ovulation. Ghrelin may modulate inflammatory signaling via growth hormone secretagogue receptors. We investigated the role of ghrelin in KGN human ovarian granulosa cells using protein kinase C (PKC) activator phorbol 12, 13-didecanoate (PDD) and synthetic ghrelin analog growth hormone releasing peptide-2 (GHRP-2). GHRP-2 attenuated PDD-induced expression of protein and mRNA, the promoter activity of COX-2 and IL-8 genes, and the secretion of prostaglandin E2 (PGE2) and IL-8. GHRP-2 promoted the degradation of PDD-induced COX-2 and IL-8 proteins with the involvement of proteasomal and lysosomal pathways. PDD-mediated COX-2 production acts via the p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways; PDD-mediated IL-8 production acts via the p38, JNK and ERK pathways. GHRP-2 reduced the PDD-induced phosphorylation of p38 and JNK and activator protein 1 (AP-1) reporter activation and PDD-induced NF-κB nuclear translocation and reporter activation. The inhibitors of mitogen-activated protein kinase phosphatase-1 (MKP-1) and protein phosphatase 2 (PP2A) reduced the inhibitory effect of GHRP-2 on PDD-induced COX-2 and IL-8 expression. Our findings demonstrate an anti-inflammatory role for ghrelin (GHRP-2) in PKC-mediated inflammation of granulosa cells, at least in part, due to its inhibitory effect on PKC-induced activation of p38, JNK and NF-κB, possibly by targeting to MKP-1 and PP2A. PMID:27548147

  11. Chrysin suppresses mast cell-mediated allergic inflammation: Involvement of calcium, caspase-1 and nuclear factor-κB

    International Nuclear Information System (INIS)

    A great number of people are suffering from allergic inflammatory diseases such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid contained in propolis, blue passion flower, and fruits. Several studies reported that chrysin has beneficial effects including anti-tumor and anti-oxidant activities. The aim of the present study was to elucidate whether chrysin modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. Chrysin inhibited immediate-type systemic hypersensitivity and serum histamine release. Chrysin attenuated immunoglobulin E-mediated local anaphylaxis. These inhibitory effects of chrysin on the systemic and local allergic reaction were more potent than cromolyn, a known anti-allergic drug. Chrysin reduced histamine release from mast cells. The inhibitory effect of chrysin on the histamine release was mediated by the modulation of intracellular calcium. In addition, chrysin decreased gene expression of pro-inflammatory cytokines such as, tumor necrosis factor-α, IL (interleukin)-1β, IL-4, and IL-6 in mast cells. The inhibitory effect of chrysin on the pro-inflammatory cytokine was nuclear factor-κB and caspase-1 dependent. Our findings provide evidence that chrysin inhibits mast cell-derived allergic inflammatory reactions by blocking histamine release and pro-inflammatory cytokine expression, and suggest the mechanisms of action. Furthermore, in vivo and in vitro anti-allergic inflammatory effect of chrysin suggests a possible therapeutic application of this agent in allergic inflammatory diseases. - Research Highlights: → Discovery of drugs for the allergic inflammation is important in human health. → Chrysin is a natural flavonoid contained in propolis, blue passion flower, and fruits. → Chrysin inhibited

  12. Eosinophilic inflammation in allergic asthma

    Directory of Open Access Journals (Sweden)

    Samantha Souza Possa

    2013-04-01

    Full Text Available Eosinophils are circulating granulocytes involved in pathogenesis of asthma. A cascade of processes directed by Th2 cytokine producing T-cells influence the recruitment of eosinophils into the lungs. Furthermore, multiple elements including interleukin (IL-5, IL-13, chemoattractants such as eotaxin, Clara cells, and CC chemokine receptor (CCR3 are already directly involved in recruiting eosinophils to the lung during allergic inflammation. Once recruited, eosinophils participate in the modulation of immune response, induction of airway hyperresponsiveness and remodeling, characteristic features of asthma. Various types of promising treatments for reducing asthmatic response are related to reduction in eosinophil counts both in human and experimental models of pulmonary allergic inflammation, showing that the recruitment of these cells really plays an important role in the pathophysiology of allergic diseases such asthma.

  13. CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.

    Directory of Open Access Journals (Sweden)

    Dennis Wolf

    Full Text Available BACKGROUND: Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L--an established marker and mediator of cardiovascular disease--induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo. METHODOLOGY/PRINCIPAL FINDINGS: WT or CD40L(-/- mice consumed a high fat diet (HFD for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L(-/- mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L(-/- mice. However, CD40L(-/- mice consuming HFD were not protected from the onset of diet-induced obesity (DIO, insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L(-/- mice consuming a low fat diet (LFD showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels. CONCLUSION: We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease.

  14. Circuit analysis method for thin-film solar cell modules

    Science.gov (United States)

    Burger, D. R.

    1985-01-01

    The design of a thin-film solar cell module is dependent on the probability of occurrence of pinhole shunt defects. Using known or assumed defect density data, dichotomous population statistics can be used to calculate the number of defects expected in a module. Probability theory is then used to assign the defective cells to individual strings in a selected series-parallel circuit design. Iterative numerical calculation is used to calcuate I-V curves using cell test values or assumed defective cell values as inputs. Good and shunted cell I-V curves are added to determine the module output power and I-V curve. Different levels of shunt resistance can be selected to model different defect levels.

  15. Mast cell adenosine receptors function: a focus on the A3 adenosine receptor and inflammation

    Directory of Open Access Journals (Sweden)

    Noam eRudich

    2012-06-01

    Full Text Available Adenosine is a metabolite, which has long been implicated in a variety of inflammatory processes. Inhaled adenosine provokes bronchoconstriction in asthmatics or chronic obstructive pulmonary disease (COPD patients, but not in non-asthmatics. This hyper responsiveness to adenosine appears to be mediated by mast cell activation. These observations have marked the receptor that mediates the bronchoconstrictor effect of adenosine on mast cells, as an attractive drug candidate. Four subtypes (A1, A2a, A2b and A3 of adenosine receptors have been cloned and shown to display distinct tissue distributions and functions. Animal models have firmly established the ultimate role of the A3 adenosine receptor (A3R in mediating hyper responsiveness to adenosine in mast cells, although the influence of the A2b adenosine receptor was confirmed as well. In contrast, studies of the A3R in humans have been controversial. In this review, we summarize data on the role of different adenosine receptors in mast cell regulation of inflammation and pathology, with a focus on the common and distinct functions of the A3R in rodent and human mast cells. The relevance of mouse studies to the human is discussed.

  16. Tyrosol Suppresses Allergic Inflammation by Inhibiting the Activation of Phosphoinositide 3-Kinase in Mast Cells.

    Directory of Open Access Journals (Sweden)

    In-Gyu Je

    Full Text Available Allergic diseases such as atopic dermatitis, rhinitis, asthma, and anaphylaxis are attractive research areas. Tyrosol (2-(4-hydroxyphenylethanol is a polyphenolic compound with diverse biological activities. In this study, we investigated whether tyrosol has anti-allergic inflammatory effects. Ovalbumin-induced active systemic anaphylaxis and immunoglobulin E-mediated passive cutaneous anaphylaxis models were used for the immediate-type allergic responses. Oral administration of tyrosol reduced the allergic symptoms of hypothermia and pigmentation in both animal models. Mast cells that secrete allergic mediators are key regulators on allergic inflammation. Tyrosol dose-dependently decreased mast cell degranulation and expression of inflammatory cytokines. Intracellular calcium levels and activation of inhibitor of κB kinase (IKK regulate cytokine expression and degranulation. Tyrosol blocked calcium influx and phosphorylation of the IKK complex. To define the molecular target for tyrosol, various signaling proteins involved in mast cell activation such as Lyn, Syk, phosphoinositide 3-kinase (PI3K, and Akt were examined. Our results showed that PI3K could be a molecular target for tyrosol in mast cells. Taken together, these findings indicated that tyrosol has anti-allergic inflammatory effects by inhibiting the degranulation of mast cells and expression of inflammatory cytokines; these effects are mediated via PI3K. Therefore, we expect tyrosol become a potential therapeutic candidate for allergic inflammatory disorders.

  17. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model.

    Science.gov (United States)

    Bonfield, Tracey L; Koloze, Mary; Lennon, Donald P; Zuchowski, Brandon; Yang, Sung Eun; Caplan, Arnold I

    2010-12-01

    Allogeneic human mesenchymal stem cells (hMSCs) introduced intravenously can have profound anti-inflammatory activity resulting in suppression of graft vs. host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases. hMSCs produce bioactive factors that provide molecular cuing for: 1) immunosuppression of T cells; 2) antiscarring; 3) angiogenesis; 4) antiapoptosis; and 5) regeneration (i.e., mitotic for host-derived progenitor cells). Studies have shown that hMSCs have profound effects on the immune system and are well-tolerated and therapeutically active in immunocompetent rodent models of multiple sclerosis and stroke. Furthermore, intravenous administration of MSCs results in pulmonary localization. Asthma is a major debilitating pulmonary disease that impacts in excess of 150 million people in the world with uncontrolled asthma potentially leading to death. In addition, the socioeconomic impact of asthma-associated illnesses at the pediatric and adult level are in the millions of dollars in healthcare costs and lost days of work. hMSCs may provide a viable multiaction therapeutic for this inflammatory lung disease by secreting bioactive factors or directing cellular activity. Our studies show the effectiveness and specificity of the hMSCs on decreasing chronic airway inflammation associated with the murine ovalbumin model of asthma. In addition, the results from these studies verify the in vivo immunoeffectiveness of hMSCs in rodents and support the potential therapeutic use of hMSCs for the treatment of airway inflammation associated with chronic asthma. PMID:20817776

  18. Cellular adhesion molecules on endothelial cells participate in radiation-mediated inflammation

    International Nuclear Information System (INIS)

    Purpose: The acute and subacute clinical manifestations of ionizing radiation mimic the inflammatory response to a number of stimuli. During the early stages of the inflammatory response, endothelial cells rapidly and transiently express a number of glycoproteins such as E-selectin, P-selectin, ICAM-1 and VCAM-1 which influence leucocyte adhesion. We quantified the expression of these cellular adhesion molecules (CAMs) in irradiated endothelial cells in order to determine whether these glycoproteins participate in radiation-mediated inflammation. Methods: Primary cultures of human umbilical vein endothelial cells (HUVEC) and HMEC cells were grown to 90% confluence and irradiated with a GE Maxitron x-ray generator. The cells were incubated with primary IgG1 antibody (mouse anti-human ICAM-1, VCAM-1, P-selectin and E-selectin and incubated with FITC-conjugated secondary antibody (goat anti-mouse IgG1). Fluorescence-activated cell sorting (FACS) analysis was utilized for quantitation of receptor expression of each CAM on irradiated endothelial cells. Electrophoretic mobility gel shift assays of nuclear protein extracts from irradiated HUVEC cells were performed using the E-selectin NFkB binding sequence (5'AGCTTAGAGGGGATTTCCGAGAGGA-3'). The E-selectin promoter was ligated to the growth hormone reporter. Plasmids pE-sel(-587 +35)GH or pE-sel(-587 +35)GH Δ NFκB (5 μg) was transfected into HMEC or HUVEC cells by use of lipofection. Transfectants were incubated for 16 h after transfection followed by treatment with 10 Gy (1 Gy/min, GE Maxitron) of ionizing radiation, and or with TNF or IL-1. Leukocyte adhesion to irradiated endothelial cells was quantified by HL-60 binding. Results: The log fluorescence of cells incubated with the antibody to E-selectin shifted by 32% at 4 h after irradiation. In comparison, a shift of 35% occurred 20 h after irradiation for cells incubated with the antibody to ICAM. However, there was no significant increase in P-selectin or VCAM

  19. Solar cell module and its manufacturing process. Taiyo denchi module oyobi sono seizo hoho

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Akihiko.

    1990-01-12

    The reason behind the high power costs of solar cells is expensiveness of solar cell element devices and its modules, and efforts to lower the costs of the former have so far been made, but the same efforts are necessary for the latter too. Concerning CdS/CdTe or CdS/CuInSe {sub 2} solar cells, when the oxygen concentration in the atmosphere available around the element device becomes less, deterioration of its performance occurs. Heretofore, concerning the above two kinds of solar cell modules, a stress was placed on prevention of infiltration of water into the element device and no concern has been paid to the effect of oxygen. Consequently, several issues have remained unsolved like alteration of crude material around the element of module with material which does not react with oxygen or absorb it. In view of the above, this invention proposes to make a solar cell module of the structure that thermosetting resin is set at the peripheral blank part of the substrate with no formation of solar cell element and a box with a flange is applied to that part in the heated and pressurized condition at the time of making protection of the back of the CdS/CdTe or CdS/CuInSe {sub 2} solar cell element device. 7 figs.

  20. Low Concentration of S100A8/9 Promotes Angiogenesis-Related Activity of Vascular Endothelial Cells: Bridges among Inflammation, Angiogenesis, and Tumorigenesis?

    Directory of Open Access Journals (Sweden)

    Changyou Li

    2012-01-01

    Full Text Available Previous studies showed that several members of the S100A family are involved in neovascularization and tumor development. This study checked whether low concentrations of S100A8 or S100A9 has any effect on the behaviour of vascular endothelial cells. A human umbilical vascular endothelial cell (HUVEC line was used to measure vascular endothelial cell bioactivity related to angiogenesis, such as cell proliferation, migration, and vessel formation. In the low concentration range up to 10 μg/mL, either each alone or in combination, S100A8 and S100A9 proteins promoted proliferation of HUVEC cells in a dose-dependent manner. The presence of both proteins in culture showed additive effects over each single protein. Both proteins enhanced HUVEC cells to migrate across the transwell membrane and to form tube-like structures on the Matrigel surface. When mixed in Matrigel and injected subcutaneously in Balb/c mice, both proteins increased vessel development in the gel plugs. Microarray assay of HUVEC cells treated with 10 μg/mL S100A8 revealed that ribosome pathway, pathogenic Escherichia coli infection pathway, apoptosis, and stress response genes were modulated by S100A8 treatment. We propose that S100A8 and S100A9 proteins from either infiltrating inflammatory cells or tumor cells play an important role in the interplay among inflammation, angiogenesis, and tumorigenesis.

  1. The cell surface receptor Slamf6 modulates innate immune responses during Citrobacter rodentium-induced colitis.

    Science.gov (United States)

    van Driel, Boaz; Wang, Guoxing; Liao, Gongxian; Halibozek, Peter J; Keszei, Marton; O'Keeffe, Michael S; Bhan, Atul K; Wang, Ninghai; Terhorst, Cox

    2015-09-01

    The homophilic cell surface receptors CD150 (Slamf1) and CD352 (Slamf6) are known to modulate adaptive immune responses. Although the Th17 response was enhanced in Slamf6(-/-) C57BL/6 mice upon oral infection with Citrobacter rodentium, the pathologic consequences are indistinguishable from an infection of wild-type C57BL/6 mice. Using a reporter-based binding assay, we show that Slamf6 can engage structures on the outer cell membrane of several Gram(-) bacteria. Therefore, we examined whether Slamf6, like Slamf1, is also involved in innate responses to bacteria and regulates peripheral inflammation by assessing the outcome of C. rodentium infections in Rag(-/-) mice. Surprisingly, the pathology and immune responses in the lamina propria of C. rodentium-infected Slamf6(-/-) Rag(-/-) mice were markedly reduced as compared with those of Rag(-/-) mice. Infiltration of inflammatory phagocytes into the lamina propria was consistently lower in Slamf6(-/-) Rag(-/-) mice than in Rag(-/-) animals. Concomitant with the reduced systemic translocation of the bacteria was an enhanced production of IL-22, suggesting that Slamf6 suppresses a mucosal protective program. Furthermore, administering a mAb (330) that inhibits bacterial interactions with Slamf6 to Rag(-/-) mice ameliorated the infection compared with a control antibody. We conclude that Slamf6-mediated interactions of colonic innate immune cells with specific Gram(-) bacteria reduce mucosal protection and enhance inflammation, contributing to lethal colitis that is caused by C. rodentium infections in Rag(-/-) mice.

  2. Biomechanical Loading Modulates Proinflammatory and Bone Resorptive Mediators in Bacterial-Stimulated PDL Cells

    Directory of Open Access Journals (Sweden)

    Andressa Vilas Boas Nogueira

    2014-01-01

    Full Text Available The present study aimed to evaluate in vitro whether biomechanical loading modulates proinflammatory and bone remodeling mediators production by periodontal ligament (PDL cells in the presence of bacterial challenge. Cells were seeded on BioFlex culture plates and exposed to Fusobacterium nucleatum ATCC 25586 and/or cyclic tensile strain (CTS of low (CTSL and high (CTSH magnitudes for 1 and 3 days. Synthesis of cyclooxygenase-2 (COX2 and prostaglandin E2 (PGE2 was evaluated by ELISA. Gene expression and protein secretion of osteoprotegerin (OPG and receptor activator of nuclear factor kappa-B ligand (RANKL were evaluated by quantitative RT-PCR and ELISA, respectively. F. nucleatum increased the production of COX2 and PGE2, which was further increased by CTS. F. nucleatum-induced increase of PGE2 synthesis was significantly (P<0.05 increased when CTSH was applied at 1 and 3 days. In addition, CTSH inhibited the F. nucleatum-induced upregulation of OPG at 1 and 3 days, thereby increasing the RANKL/OPG ratio. OPG and RANKL mRNA results correlated with the protein results. In summary, our findings provide original evidence that CTS can enhance bacterial-induced syntheses of molecules associated with inflammation and bone resorption by PDL cells. Therefore, biomechanical, such as orthodontic or occlusal, loading may enhance the bacterial-induced inflammation and destruction in periodontitis.

  3. Lysophospholipid Receptors, as Novel Conditional Danger Receptors and Homeostatic Receptors Modulate Inflammation-Novel Paradigm and Therapeutic Potential.

    Science.gov (United States)

    Wang, Xin; Li, Ya-Feng; Nanayakkara, Gayani; Shao, Ying; Liang, Bin; Cole, Lauren; Yang, William Y; Li, Xinyuan; Cueto, Ramon; Yu, Jun; Wang, Hong; Yang, Xiao-Feng

    2016-08-01

    There are limitations in the current classification of danger-associated molecular patterns (DAMP) receptors. To overcome these limitations, we propose a new paradigm by using endogenous metabolites lysophospholipids (LPLs) as a prototype. By utilizing a data mining method we pioneered, we made the following findings: (1) endogenous metabolites such as LPLs at basal level have physiological functions; (2) under sterile inflammation, expression of some LPLs is elevated. These LPLs act as conditional DAMPs or anti-inflammatory homeostasis-associated molecular pattern molecules (HAMPs) for regulating the progression of inflammation or inhibition of inflammation, respectively; (3) receptors for conditional DAMPs and HAMPs are differentially expressed in human and mouse tissues; and (4) complex signaling mechanism exists between pro-inflammatory mediators and classical DAMPs that regulate the expression of conditional DAMPs and HAMPs. This novel insight will facilitate identification of novel conditional DAMPs and HAMPs, thus promote development of new therapeutic targets to treat inflammatory disorders.

  4. Inhibitors of inflammation and endogenous surfactant pool size as modulators of lung injury with initiation of ventilation in preterm sheep

    Directory of Open Access Journals (Sweden)

    Polglase Graeme R

    2010-10-01

    Full Text Available Abstract Background Increased pro-inflammatory cytokines in tracheal aspirates correlate with the development of BPD in preterm infants. Ventilation of preterm lambs increases pro-inflammatory cytokines and causes lung inflammation. Objective We tested the hypothesis that selective inhibitors of pro-inflammatory signaling would decrease lung inflammation induced by ventilation in preterm newborn lambs. We also examined if the variability in injury response was explained by variations in the endogenous surfactant pool size. Methods Date-mated preterm lambs (n = 28 were operatively delivered and mechanically ventilated to cause lung injury (tidal volume escalation to 15 mL/kg by 15 min at age. The lambs then were ventilated with 8 mL/kg tidal volume for 1 h 45 min. Groups of animals randomly received specific inhibitors for IL-8, IL-1, or NF-κB. Unventilated lambs (n = 7 were the controls. Bronchoalveolar lavage fluid (BALF and lung samples were used to quantify inflammation. Saturated phosphatidylcholine (Sat PC was measured in BALF fluid and the data were stratified based on a level of 5 μmol/kg (~8 mg/kg surfactant. Results The inhibitors did not decrease the cytokine levels or inflammatory response. The inflammation increased as Sat PC pool size in BALF decreased. Ventilated lambs with a Sat PC level > 5 μmol/kg had significantly decreased markers of injury and lung inflammation compared with those lambs with Conclusion Lung injury caused by high tidal volumes at birth were decreased when endogenous surfactant pool sizes were larger. Attempts to decrease inflammation by blocking IL-8, IL-1 or NF-κB were unsuccessful.

  5. Plumbagin Modulates Leukemia Cell Redox Status

    Directory of Open Access Journals (Sweden)

    François Gaascht

    2014-07-01

    Full Text Available Plumbagin is a plant naphtoquinone exerting anti-cancer properties including apoptotic cell death induction and generation of reactive oxygen species (ROS. The aim of this study was to elucidate parameters explaining the differential leukemia cell sensitivity towards this compound. Among several leukemia cell lines, U937 monocytic leukemia cells appeared more sensitive to plumbagin treatment in terms of cytotoxicity and level of apoptotic cell death compared to more resistant Raji Burkitt lymphoma cells. Moreover, U937 cells exhibited a ten-fold higher ROS production compared to Raji. Neither differential incorporation, nor efflux of plumbagin was detected. Pre-treatment with thiol-containing antioxidants prevented ROS production and subsequent induction of cell death by apoptosis whereas non-thiol-containing antioxidants remained ineffective in both cellular models. We conclude that the anticancer potential of plumbagin is driven by pro-oxidant activities related to the cellular thiolstat.

  6. Sensitivity of laser flare photometry compared to slit-lamp cell evaluation in monitoring anterior chamber inflammation in uveitis.

    Science.gov (United States)

    Bernasconi, Ottavio; Papadia, Marina; Herbort, Carl P

    2010-10-01

    To study the sensitivity of laser flare photometry (LFP) in monitoring anterior chamber inflammation by correlating LFP measurements with slit-lamp evaluation of aqueous cells in HLA-B27-related uveitis in a prospective trial. Slit-lamp cell evaluation was correlated with LFP-measured flare in a masked fashion in HLA-B27-related uveitis patients receiving standard topical therapy. At the time of 50 and 90% LFP flare reduction, the corresponding reduction of cells was recorded and statistically compared using the sign test. Forty-three episodes (in 43 patients) of acute anterior HLA-B27-related uveitis were included. LFP flare reduction and slit-lamp cell reduction were strongly correlated. LFP was significantly more sensitive for both 50% (P = 0.001) and 90% (P = 0.02) LFP flare reduction in assessing the decrease of anterior chamber inflammation. LFP was superior to slit-lamp cell evaluation in monitoring anterior chamber inflammation in uveitis. Flare, becoming a quantitative parameter when measured by LFP, rather than cells, should be considered the gold standard to measure anterior chamber inflammation in uveitis. PMID:20686916

  7. Bacterial Probiotic Modulation of Dendritic Cells

    OpenAIRE

    Drakes, Maureen; Blanchard, Thomas; Czinn, Steven

    2004-01-01

    Intestinal dendritic cells are continually exposed to ingested microorganisms and high concentrations of endogenous bacterial flora. These cells can be activated by infectious agents and other stimuli to induce T-cell responses and to produce chemokines which recruit other cells to the local environment. Bacterial probiotics are of increasing use against intestinal disorders such as inflammatory bowel disease. They act as nonpathogenic stimuli within the gut to regain immunologic quiescence. ...

  8. Anti-HMGB1 Neutralizing Antibody Ameliorates Neutrophilic Airway Inflammation by Suppressing Dendritic Cell-Mediated Th17 Polarization

    Directory of Open Access Journals (Sweden)

    Fang Zhang

    2014-01-01

    Full Text Available We demonstrate that high mobility group box 1 protein (HMGB1 directs Th17 skewing by regulating dendritic cell (DC function. First, our in vitro studies reveal that recombinant HMGB1 (rHMGB1 activates myeloid DCs to produce IL-23 in vitro, and rHMGB1-activated DCs prime naïve lymphocytes to produce the Th17 cytokine IL-17A. Second, we demonstrate that anti-HMGB1 neutralizing antibody attenuates HMGB1 expression, neutrophilic inflammation, airway hyperresponsiveness, and Th17-related cytokine secretion in vivo by using a murine model of neutrophilic asthma induced by ovalbumin (OVA plus lipopolysaccharide (LPS. Furthermore, anti-HMGB1 neutralizing antibody decreases the number of Th17 cells in lung cells and suppresses the production of IL-23 by lung CD11C+ APCs. Finally, we show that intranasal adoptive transfer of rHMGB1-activated DCs was sufficient to restore lung neutrophilic inflammation and the Th17 response in a DC-driven model of asthma, whereas the transfer of rHMGB1 plus anti-HMGB1-treated mDCs significantly reduced these inflammation phenotypes. These data suggest, for the first time, that HMGB1 drives the DC-polarized Th17-type response in allergic lung inflammation and that blocking HMGB1 may benefit the attenuation of neutrophilic airway inflammation in asthma.

  9. Airborne Fine Particulate Matter Induces Oxidative Stress and Inflammation in Human Nasal Epithelial Cells.

    Science.gov (United States)

    Hong, Zhicong; Guo, Zhiqiang; Zhang, Ruxin; Xu, Jian; Dong, Weiyang; Zhuang, Guoshun; Deng, Congrui

    2016-01-01

    Airborne fine particulate matter with an aerodynamic diameter equal to or smaller than 2.5 μm is abbreviated as PM2.5, which is one of the main components in air pollution. Exposure to PM2.5 is associated with increased risk of many human diseases, including chronic and allergic rhinitis, but the underlying molecular mechanism for its toxicity has not been fully elucidated. We have hypothesized that PM2.5 may cause oxidative stress and enhance inflammatory responses in nasal epithelial cells. Accordingly, we used human RPMI 2650 cells, derived from squamous cell carcinoma of the nasal septum, as a model of nasal epithelial cells, and exposed them to PM2.5 that was collected at Fudan University (31.3°N, 121.5°E) in Shanghai, China. PM2.5 exposure decreased the viability of RPMI 2650 cells, suggesting that PM2.5 may impair the barrier function of nasal epithelial cells. Moreover, PM2.5 increased the levels of intracellular reactive oxygen species (ROS) and the nuclear translocation of NF-E2-related factor-2 (Nrf2). Importantly, PM2.5 also decreased the activities of superoxide dismutase, catalase and glutathione peroxidase. Pretreatment with N-Acetyl-L-cysteine (an anti-oxidant) reduced the degree of the PM2.5-induced oxidative stress in RPMI 2650 cells. In addition, PM2.5 increased the production of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, interleukin-13 and eotaxin (C-C motif chemokine ligand 11), each of which initiates and/or augments local inflammation. These results suggest that PM2.5 may induce oxidative stress and inflammatory responses in human nasal epithelial cells, thereby leading to nasal inflammatory diseases. The present study provides insights into cellular injury induced by PM2.5.

  10. Platelets in inflammation and infection.

    Science.gov (United States)

    Jenne, Craig N; Kubes, Paul

    2015-01-01

    Although platelets are traditionally recognized for their central role in hemostasis, many lines of research clearly demonstrate these rather ubiquitous blood components are potent immune modulators and effectors. Platelets have been shown to directly recognize, sequester and kill pathogens, to activated and recruit leukocytes to sites of infection and inflammation, and to modulate leukocyte behavior, enhancing their ability to phagocytose and kill pathogens and inducing unique effector functions, such as the production of Neutrophil Extracellular Traps (NETs). This multifaceted response to infection and inflammation is due, in part, to the huge array of soluble mediators and cell surface molecules expressed by platelets. From their earliest origins as primordial hemocytes in invertebrates to their current form as megakaryocyte-derived cytoplasts, platelets have evolved to be one of the key regulators of host intravascular immunity and inflammation. In this review, we present the diverse roles platelets play in immunity and inflammation associated with autoimmune diseases and infection. Additionally, we highlight recent advances in our understanding of platelet behavior made possible through the use of advanced imaging techniques that allow us to visualize platelets and their interactions, in real-time, within the intact blood vessels of a living host.

  11. Application of crystalline silicon solar cells in photovoltaic modules

    Directory of Open Access Journals (Sweden)

    L.A. Dobrzański

    2010-08-01

    Full Text Available Purpose: The aim of the paper is to determinate basic electrical properties of solar cells, made of them photovoltaic module and analysis of its main electrical parameters.Design/methodology/approach: In this study, several methods were used: current – voltage characteristic to determinate basic electrical properties of 36 monocrystalline silicon solar cells, soft soldering technique to bond solar cells . Photovoltaic module was produced from 31 solar cells with the largest short-circuit current, which were joined in series.Findings: In order to obtain a device producing an electrical current with a higher current and voltage level, solar cells were connected in a photovoltaic module and then protected from damages derived from external factors. In series connection solar cell with the lowest current determines the current flowing in the PV module. Taking this fact into account the analysis of photovoltaic module construction was performed.Practical implications: Because of low operating cost and simplicity of photovoltaic installation, photovoltaic technology is perfectly suitable for supplying objects which are beyond powers network range as well as connected to it. In many cases, they are less costly option than a direct extension of the power network.Originality/value: Protecting the environment from degradation due to pollution, which has source in conventional power industry, as well as diminishing resources of fossil fuels, tend to increase development of renewable energy production such as photovoltaic technology.

  12. Mesenchymal stromal cells mediate Aspergillus hyphal extract-induced allergic airway inflammation by inhibition of the Th17 signaling pathway.

    Science.gov (United States)

    Lathrop, Melissa J; Brooks, Elice M; Bonenfant, Nick R; Sokocevic, Dino; Borg, Zachary D; Goodwin, Meagan; Loi, Roberto; Cruz, Fernanda; Dunaway, Chad W; Steele, Chad; Weiss, Daniel J

    2014-02-01

    Systemic administration of mesenchymal stromal cells (MSCs) suppresses airway inflammation and methacholine-induced airway hyper-responsiveness (AHR) in mouse models of T helper cell (Th) type 2-mediated eosinophilic allergic airway inflammation (AAI); however, the efficacy of MSCs in mouse models of severe Th17-mediated neutrophilic AAI has not yet been demonstrated. We assessed MSC effects in a mouse model of mixed Th2/Th17 AAI produced by mucosal exposure to Aspergillus fumigatus hyphal extract (AHE). Following sensitization produced by oropharyngeal AHE administration, systemic (tail vein) administration of syngeneic MSCs on the first day of challenge significantly reduced acute AHR predominantly through reduction of Th17-mediated airway inflammation. In parallel experiments, MSCs also mitigated AHR when administered during recurrent challenge 10 weeks after initial sensitization and challenge through reduction in systemic Th17-mediated inflammation. Investigation into potential mechanistic actions of MSCs in this model demonstrated that although T regulatory cells were increased in all AHE-treated mice, MSC administration did not alter T regulatory cell numbers in either the acute or recurrent model. Differential induction of interleukin-17a secretion was observed in ex vivo restimulation of mediastinal lymph node mixed-cell cytokine analyses. Although the mechanisms by which MSCs act to decrease inflammation and AHR in this model are not yet fully elucidated, decrease in Th17-mediated airway inflammation appears to play a significant role. These results provide a basis for further investigations of MSC administration as a potential therapeutic approach for severe refractory neutrophilic asthma. PMID:24436442

  13. Hydrogen sulfide improves colonic barrier integrity in DSS-induced inflammation in Caco-2 cells and mice.

    Science.gov (United States)

    Zhao, Hongyu; Yan, Rui; Zhou, Xiaogang; Ji, Fang; Zhang, Bing

    2016-10-01

    Intestinal barrier involves in the pathogeny of inflammatory bowel disease (IBD) and hydrogen sulfide (H2S) has been reported to improve intestinal barrier integrity. Thus, this study investigated the effects of GYY4137, a slow-release H2S donor, on DSS-induced inflammation and intestinal dysfunction. In vitro model, cellular permeability was significantly increased and expression of tight junctions (ZO-1, Cauldin4, and Occludin) was downregulated in Caco-2 cells. GYY4137 treatment markedly attenuated DSS-induced inflammation and barrier dysfunction. Cystathionine β-synthase (CBS)-siRNA transfection further demonstrated that endogenous H2S system involves in DSS-induced inflammation and mediates barrier function. In vivo model, DSS exposure caused colonic inflammation and injury in mice and GYY4137 injection alleviated inflammatory response and improved intestinal barrier via reducing intestinal permeability and upregulating of tight junctions. In conclusion, endogenous H2S system involves in DSS-induced inflammation and H2S addition alleviated inflammation and intestinal dysfunction in vitro and in vivo.

  14. Mast cells modulate acute toxoplasmosis in murine models.

    Directory of Open Access Journals (Sweden)

    Bo Huang

    Full Text Available The role of mast cells (MCs in Toxoplasma gondii infection is poorly known. Kunming outbred mice were infected intraperitoneally with RH strain T. gondii, either treated with compound 48/80 (C48/80, MC activator or disodium cromoglycate (DSCG, MC inhibitor. Compared with infected controls, infected mice treated with C48/80 exhibited significantly increased inflammation in the liver (P < 0.01, spleen (P < 0.05, and mesentery (P < 0.05 tissues, higher parasite burden in the peritoneal lavage fluids (P < 0.01, and increased levels of mRNA transcripts of T. gondii tachyzoite surface antigen 1 (SAG1 gene in the spleen and liver tissues (P < 0.01, accompanied with significantly increased Th1 cytokine (IFN-γ, IL-12p40, and TNF-α (P < 0.01 and decreased IL-10 (P < 0.01 mRNA expressions in the liver, and increased IFN-γ (P < 0.01 and IL-12p40 (P < 0.01 but decreased TNF-α (P < 0.01 and IL-4 (P < 0.01 in the spleens of infected mice treated with C48/80 at day 9-10 p.i. Whereas mice treated with DSCG had significantly decreased tissue lesions (P < 0.01, lower parasite burden in the peritoneal lavage fluids (P < 0.01 and decreased SAG1 expressions in the spleen and liver tissues (P < 0.01, accompanied with significantly increased IFN-γ (P < 0.01 and IL-12p40 (P < 0.05 in the liver, and decreased IFN-γ (P < 0.05 and TNF-α (P < 0.01 in the spleens; IL-4 and IL-10 expressions in both the spleen and liver were significantly increased (P < 0.01 in the infected mice treated with DSCG. These findings suggest that mediators associated with the MC activation may play an important role in modulating acute inflammatory pathogenesis and parasite clearance during T. gondii infection in this strain of mice. Thus, MC activation/inhibition mechanisms are potential novel targets for the prevention and control of T. gondii infection.

  15. Heparin-disaccharide affects T cells: inhibition of NF-kappaB activation, cell migration, and modulation of intracellular signaling.

    Science.gov (United States)

    Hecht, Iris; Hershkoviz, Rami; Shivtiel, Shoham; Lapidot, Tzvi; Cohen, Irun R; Lider, Ofer; Cahalon, Liora

    2004-06-01

    We previously reported that disaccharides (DS), generated by enzymatic degradation of heparin or heparan sulfate, inhibit T cell-mediated immune reactions in rodents and regulate cytokine [tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-8, and IL-1beta] secretion by T cells, macrophages, or intestinal epithelial cells. Here, we investigated the effects of a trisulfated heparin DS (3S-DS) on two aspects of T cell function: secretion of proinflammatory cytokines and migration to an inflamed site. 3S-DS down-regulated nuclear factor-kappaB activity and reduced the secretion of TNF-alpha and interferon-gamma (IFN-gamma) by anti-CD3-activated T cells. In addition, 3S-DS inhibited CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor-1alpha)-dependent migration in vitro and in vivo and decreased CXCL12-induced T cell adhesion to the extracellular matrix glycoprotein, fibronectin (FN). This inhibition was accompanied by attenuation of CXCL12-induced Pyk2 phosphorylation but did not involve internalization of the CXCL12 receptor, CXCR4, or phosphorylation of extracellular-regulated kinase. Despite inhibiting CXCL12-induced adhesion, 3S-DS, on its own, induced T cell adhesion to FN, which was accompanied by phosphorylation of Pyk2. A monosulfated DS showed no effect. Taken together, these data provide evidence that 3S-DS can regulate inflammation by inducing and modulating T cell-signaling events, desensitizing CXCR4, and modulating T cell receptor-induced responses. PMID:15020655

  16. Applications of ``PV Optics`` for solar cell and module design

    Energy Technology Data Exchange (ETDEWEB)

    Sopori, B.L.; Madjdpour, J.; Chen, W. [National Renewable Energy Lab., Golden, CO (United States)

    1998-09-01

    This paper describes some applications of a new optics software package, PV Optics, developed for the optical design of solar cells and modules. PV Optics is suitable for the analysis and design of both thick and thin solar cells. It also includes a feature for calculation of metallic losses related to contacts and back reflectors.

  17. Enforced expression of Gata3 in T cells and group 2 innate lymphoid cells increases susceptibility to allergic airway inflammation in mice

    NARCIS (Netherlands)

    A. Kleinjan (Alex); R.G.J. Klein Wolterink (Roel); Y. Levani (Yelvi); M.J.W. de Bruijn (Marjolein); H.C. Hoogsteden (Henk); M. van Nimwegen (Menno); R.W. Hendriks (Rudi)

    2014-01-01

    textabstractAirway inflammation in allergic asthma reflects a threshold response of the innate immune system, including group 2 innate lymphoid cells (ILC2), followed by an adaptive Th2 cell-mediated response. Transcription factor Gata3 is essential for differentiation of both Th2 cells and ILC2. We

  18. The sickle cell mouse lung: proinflammatory and primed for allergic inflammation.

    Science.gov (United States)

    Andemariam, Biree; Adami, Alexander J; Singh, Anurag; McNamara, Jeffrey T; Secor, Eric R; Guernsey, Linda A; Thrall, Roger S

    2015-09-01

    Comorbid asthma in sickle cell disease (SCD) confers higher rates of vaso-occlusive pain and mortality, yet the physiological link between these two distinct diseases remains puzzling. We used a mouse model of SCD to study pulmonary immunology and physiology before and after the induction of allergic airway disease (AAD). SCD mice were sensitized with ovalbumin (OVA) and aluminum hydroxide by the intraperitoneal route followed by daily, nose-only OVA-aerosol challenge to induce AAD. The lungs of naive SCD mice showed signs of inflammatory and immune processes: (1) histologic and cytochemical evidence of airway inflammation compared with naive wild-type mice; (2) bronchoalveolar lavage (BAL) fluid contained increased total lymphocytes, %CD8+ T cells, granulocyte-colony stimulating factor, interleukin 5 (IL-5), IL-7, and chemokine (C-X-C motif) ligand (CXCL)1; and (3) lung tissue and hilar lymph node (HLN) had increased CD4+, CD8+, and regulatory T (Treg) cells. Furthermore, SCD mice at AAD demonstrated significant changes compared with the naive state: (1) BAL fluid with increased %CD4+ T cells and Treg cells, lower %CD8+ T cells, and decreased interferon gamma, CXCL10, chemokine (C-C motif) ligand 2, and IL-17; (2) serum with increased OVA-specific immunoglobulin E, IL-6, and IL-13, and decreased IL-1α and CXCL10; (3) no increase in Treg cells in the lung tissue or HLN; and (4) hyporesponsiveness to methacholine challenge. In conclusion, SCD mice have an altered immunologic pulmonary milieu and physiological responsiveness. These findings suggest that the clinical phenotype of AAD in SCD mice differs from that of wild-type mice and that individuals with SCD may also have a unique, divergent phenotype perhaps amenable to a different therapeutic approach. PMID:25843670

  19. Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and Inflammation

    Directory of Open Access Journals (Sweden)

    Io-Guané Rivera

    2015-04-01

    Full Text Available Sphingolipids are major constituents of biological membranes of eukaryotic cells. Many studies have shown that sphingomyelin (SM is a major phospholipid in cell bilayers and is mainly localized to the plasma membrane of cells, where it serves both as a building block for cell architecture and as a precursor of bioactive sphingolipids. In particular, upregulation of (C-type sphingomyelinases will produce ceramide, which regulates many physiological functions including apoptosis, senescence, or cell differentiation. Interestingly, the venom of some arthropodes including spiders of the genus Loxosceles, or the toxins of some bacteria such as Corynebacterium tuberculosis, or Vibrio damsela possess high levels of D-type sphingomyelinase (SMase D. This enzyme catalyzes the hydrolysis of SM to yield ceramide 1-phosphate (C1P, which promotes cell growth and survival and is a potent pro-inflammatory agent in different cell types. In particular, C1P stimulates cytosolic phospholipase A2 leading to arachidonic acid release and the subsequent formation of eicosanoids, actions that are all associated to the promotion of inflammation. In addition, C1P potently stimulates macrophage migration, which has also been associated to inflammatory responses. Interestingly, this action required the interaction of C1P with a specific plasma membrane receptor, whereas accumulation of intracellular C1P failed to stimulate chemotaxis. The C1P receptor is coupled to Gi proteins and activates of the PI3K/Akt and MEK/ERK1-2 pathways upon ligation with C1P. The proposed review will address novel aspects on the control of inflammatory responses by C1P and will highlight the molecular mechanisms whereby C1P exerts these actions.

  20. Transparent electrode requirements for thin film solar cell modules

    KAUST Repository

    Rowell, Michael W.

    2011-01-01

    The transparent conductor (TC) layer in thin film solar cell modules has a significant impact on the power conversion efficiency. Reflection, absorption, resistive losses and lost active area either from the scribed interconnect region in monolithically integrated modules or from the shadow losses of a metal grid in standard modules typically reduce the efficiency by 10-25%. Here, we perform calculations to show that a competitive TC must have a transparency of at least 90% at a sheet resistance of less than 10 Ω/sq (conductivity/absorptivity ≥ 1 Ω -1) for monolithically integrated modules. For standard modules, losses are much lower and the performance of alternative lower cost TC materials may already be sufficient to replace conducting oxides in this geometry. © 2011 The Royal Society of Chemistry.

  1. Modulation transfer spectroscopy in a lithium atomic vapor cell.

    Science.gov (United States)

    Sun, Dali; Zhou, Chao; Zhou, Lin; Wang, Jin; Zhan, Mingsheng

    2016-05-16

    We have investigated modulation transfer spectroscopy of D2 transitions of 7Li atoms in a vapor cell. The role of the intensity of the probe beam in the spectrum is important, we have seen unique characteristics of the signal in the crossover peak. In order to find the best signal for laser locking, the slope and frequency offset of the zero-crossing signal are determined. The dependence of the modulation transfer spectra on polarizations of pump and probe beam is demonstrated. The residual amplitude modulation in the system is also considered, and the distortion of the spectra due to the modulation is analyzed. It was found that the crossover peak is more suitable for frequency stabilization due to its better residual amplitude modulation compensation. PMID:27409886

  2. The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in humans*

    Science.gov (United States)

    Background: The Glutathione-S-Transferase Mu 1 null genotype has been reported to be a risk factor for acute respiratory disease associated with increases in ambient air ozone. Ozone is known to cause an immediate decrease in lung function and increased airway inflammation. Howev...

  3. The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: A systems biology approach

    NARCIS (Netherlands)

    Calçada, D.; Vianello, D.; Giampieri, E.; Sala, C.; Castellani, G.; Graaf, A.A. de; Kremer, S.H.A.; Ommen, B. van; Feskens, E.; Santoro, A.; Franceschi, C.; Bouwman, J.

    2014-01-01

    Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabolic

  4. Cereal based diets modulate some markers of oxidative stress and inflammation in lean and obese Zucker rats

    Directory of Open Access Journals (Sweden)

    Mano Mark

    2011-05-01

    Full Text Available Abstract Background The potential of cereals with high antioxidant capacity for reducing oxidative stress and inflammation in obesity is unknown. This study investigated the impact of wheat bran, barley or a control diet (α-cellulose on the development of oxidative stress and inflammation in lean and obese Zucker rats. Methods Seven wk old, lean and obese male Zucker rats (n = 8/group were fed diets that contained wheat bran, barley or α-cellulose (control. After 3 months on these diets, systolic blood pressure was measured and plasma was analysed for glucose, insulin, lipids, oxygen radical absorbance capacity (ORAC, malondialdehyde, glutathione peroxidase and adipokine concentration (leptin, adiponectin, interleukin (IL-1β, IL-6, TNFα, plasminogen activator inhibitor (PAI-1, monocyte chemotactic protein (MCP-1. Adipokine secretion rates from visceral and subcutaneous adipose tissue explants were also determined. Results Obese rats had higher body weight, systolic blood pressure and fasting blood lipids, glucose, insulin, leptin and IL-1β in comparison to lean rats, and these measures were not reduced by consumption of wheat bran or barley based diets. Serum ORAC tended to be higher in obese rats fed wheat bran and barley in comparison to control (p = 0.06. Obese rats had higher plasma malondialdehyde (p Conclusions A 3-month dietary intervention was sufficient for Zucker obese rats to develop oxidative stress and systemic inflammation. Cereal-based diets with moderate and high antioxidant capacity elicited modest improvements in indices of oxidative stress and inflammation.

  5. Points of control exerted along the macrophage-endothelial cell-polymorphonuclear neutrophil axis by PECAM-1 in the innate immune response of acute colonic inflammation.

    Science.gov (United States)

    Sugimoto, Naohito; Rui, Tao; Yang, Min; Bharwani, Sulaiman; Handa, Osamu; Yoshida, Norimasa; Yoshikawa, Toshikazu; Kvietys, Peter R

    2008-08-01

    PECAM-1 is expressed on endothelial cells and leukocytes. Its extracellular domain has been implicated in leukocyte diapedesis. In this study, we used PECAM-1(-/-) mice and relevant cells derived from them to assess the role of PECAM-1 in an experimental model of acute colonic inflammation with a predominant innate immune response, i.e., 2,4,6-trinitrobenzine sulfonic acid (TNBS). Using chimeric approaches, we addressed the points of control exerted by PECAM-1 along the macrophage-endothelial cell-polymorphonuclear neutrophil (PMN) axis. In vivo, TNBS-induced colitis was ameliorated in PECAM-1(-/-) mice, an event attributed to PECAM-1 on hematopoietic cells rather than to PECAM-1 on endothelial cells. The in vivo innate immune response was mimicked in vitro by using a construct of the vascular-interstitial interface, i.e., PMN transendothelial migration was induced by colonic lavage fluid (CLF) from TNBS mice or macrophages (MPhi) challenged with CLF. Using the construct, we confirmed that endothelial cell PECAM-1 does not play a role in PMN transendothelial migration. Although MPhi activation (NF-kappaB nuclear binding) and function (keratinocyte-derived chemokine production) induced by CLF was diminished in PECAM-1(-/-) MPhi, this did not affect their ability to promote PMN transendothelial migration. By contrast, PECAM-1(-/-) PMN did not adhere to or migrate across endothelial cell monolayers in response to CLF. Further, as compared with PECAM-1(+/+) PMN, PECAM-1(-/-) PMN were less effective in orientating their CXCR2 receptors (polarization) in the direction of a chemotactic gradient. Collectively, our findings indicate that PECAM-1 modulation of PMN function (at a step before diapedesis) most likely contributes to the inflammation in a colitis model with a strong innate immune component. PMID:18641353

  6. Crotoxin from Crotalus durissus terrificus is able to down-modulate the acute intestinal inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Caroline de Souza Almeida

    Full Text Available Inflammatory bowel diseases (IBD is the result of dysregulation of mucosal innate and adaptive immune responses. Factors such as genetic, microbial and environmental are involved in the development of these disorders. Accordingly, animal models that mimic human diseases are tools for the understanding the immunological processes of the IBD as well as to evaluate new therapeutic strategies. Crotoxin (CTX is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the modulatory effect of CTX in a murine model of colitis induced by 2,4,6- trinitrobenzene sulfonic acid (TNBS. The CTX was administered intraperitoneally 18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX administration resulted in decreased weight loss, disease activity index (DAI, macroscopic tissue damage, histopathological score and myeloperoxidase (MPO activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of TNF-α, IL-1β and IL-6 were lower in colon tissue homogenates of TNBS-mice that received the CTX when compared with untreated TNBS mice. The analysis of distinct cell populations obtained from the intestinal lamina propria showed that CTX reduced the number of group 3 innate lymphoid cells (ILC3 and Th17 population; CTX decreased IL-17 secretion but did not alter the frequency of CD4+Tbet+ T cells induced by TNBS instillation in mice. In contrast, increased CD4+FoxP3+ cell population as well as secretion of TGF-β, prostaglandin E2 (PGE2 and lipoxin A4 (LXA4 was observed in TNBS-colitis mice treated with CTX compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to modulate the intestinal acute inflammatory response induced by TNBS, resulting in the improvement of clinical status of the mice. This effect of CTX is complex and involves the suppression of the pro-inflammatory environment elicited by intrarectal instillation of TNBS due to the

  7. Predomination of IL-17-producing tryptase-positive/chymase-positive mast cells in azoospermic chronic testicular inflammation.

    Science.gov (United States)

    Chen, S-J; Duan, Y-G; Haidl, G; Allam, J-P

    2016-08-01

    Chronic testicular inflammation and infection have been regarded as important factors in the pathogenesis of azoospermia. As key effector cells in innate and adaptive immune system, mast cells (MCs) were observed in inflammation and autoimmune disease. Furthermore, increased expression of tryptase-positive MCs has been reported in testicular disorders associated with male infertility/subfertility. However, little is known about the potential relationship between MCs and chronic testicular inflammation in azoospermic patients. Moreover, the preferential expression of MCs' subtypes in testis of these patients is still far from being understood. Thus, this study aimed to investigate characteristics of testicular MCs as well as their subtypes in azoospermic men with chronic testicular inflammation (AZI, n = 5) by immunohistochemical techniques. Our results showed significant increase of MCs in AZI, and more importantly, considerable numbers of tryptase-positive/chymase-positive MCs could also be demonstrated in AZI, when compared to control groups representing azoospermia without chronic testicular inflammation (AZW, n = 5) and normal spermatogenesis (NT, n = 5) respectively. Most interestingly, immunofluorescence staining revealed autoimmune-associated interleukin (IL)-17-producing MCs in AZI, whereas co-expression of MC markers with tumour necrosis factor (TNF)-α, IL-10 and IL-1β could not be detected. In conclusion, AZI is associated with significant increase of tryptase-positive/chymase-positive MCs expressing IL-17, and these MCs might contribute to the pathogenesis of AZI. PMID:26420243

  8. The Mushroom Agaricus blazei Murill Elicits Medicinal Effects on Tumor, Infection, Allergy, and Inflammation through Its Modulation of Innate Immunity and Amelioration of Th1/Th2 Imbalance and Inflammation

    Directory of Open Access Journals (Sweden)

    Geir Hetland

    2011-01-01

    Full Text Available The medicinal mushroom Agaricus blazei Murill from the Brazilian rain forest has been used in traditional medicine and as health food for the prevention of a range of diseases, including infection, allergy, and cancer. Other scientists and we have examined whether there is scientific evidence behind such postulations. Agaricus blazei M is rich in the immunomodulating polysaccharides, β-glucans, and has been shown to have antitumor, anti-infection, and antiallergic/-asthmatic properties in mouse models, in addition to anti-inflammatory effects in inflammatory bowel disease patients. These effects are mediated through the mushroom's stimulation of innate immune cells, such as monocytes, NK cells, and dendritic cells, and the amelioration of a skewed Th1/Th2 balance and inflammation.

  9. Linalool Inhibits LPS-Induced Inflammation in BV2 Microglia Cells by Activating Nrf2.

    Science.gov (United States)

    Li, Yang; Lv, Ou; Zhou, Fenggang; Li, Qingsong; Wu, Zhichao; Zheng, Yongri

    2015-07-01

    Linalool, a natural compound of the essential oils, has been reported to have anti-inflammatory effects. This study aimed to investigate the anti-inflammatory effects and mechanism of linalool in LPS-stimulated BV2 microglia cells. BV2 microglia cells were stimulated with LPS in the presence or absence of linalool. The production of inflammatory mediators TNF-α, IL-1β, NO, and PGE2 as well as Nrf2, HO-1 expression were detected. Our results showed that linalool inhibited LPS-induced TNF-α, IL-1β, NO, and PGE2 production in a dose-dependent manner. Linalool also inhibited LPS-induced NF-κB activation. Treatment of linalool induced nuclear translocation of Nrf2 and expression of HO-1. In addition, our results showed that the anti-inflammatory effect of linalool was attenuated by transfection with Nrf2 siRNA. In conclusion, these results suggested that linalool inhibits LPS-induced inflammation in BV2 microglia cells by activating Nrf2/HO-1 signaling pathway.

  10. The Protective Effect of Melatonin on Neural Stem Cell against LPS-Induced Inflammation

    Directory of Open Access Journals (Sweden)

    Juhyun Song

    2015-01-01

    Full Text Available Stem cell therapy for tissue regeneration has several limitations in the fact that transplanted cells could not survive for a long time. For solving these limitations, many studies have focused on the antioxidants to increase survival rate of neural stem cells (NSCs. Melatonin, an antioxidant synthesized in the pineal gland, plays multiple roles in various physiological mechanisms. Melatonin exerts neuroprotective effects in the central nervous system. To determine the effect of melatonin on NSCs which is in LPS-induced inflammatory stress state, we first investigated nitric oxide (NO production and cytotoxicity using Griess reagent assays, LDH assay, and neurosphere counting. Also, we investigated the effect of melatonin on NSCs by measuring the mRNA levels of SOX2, TLX, and FGFR-2. In addition, western blot analyses were performed to examine the activation of PI3K/Akt/Nrf2 signaling in LPS-treated NSCs. In the present study, we suggested that melatonin inhibits NO production and protects NSCs against LPS-induced inflammatory stress. In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Based on our results, we conclude that melatonin may be an important factor for the survival and proliferation of NSCs in neuroinflammatory diseases.

  11. Tartary buckwheat on nitric oxide-induced inflammation in RAW264.7 macrophage cells.

    Science.gov (United States)

    Choi, Soo Yeon; Choi, Ji Yeon; Lee, Jeong Min; Lee, Sanghyun; Cho, Eun Ju

    2015-08-01

    We investigated the effects of tartary buckwheat (TB, Fagopyrum tataricum) on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)- and interferon (IFN)-γ-stimulated RAW264.7 cells. We evaluated the anti-inflammatory effects of TB against the LPS- and IFN-γ-stimulated inflammatory response in RAW264.7 macrophage cells. We fractionated TB to obtain 4 fractions including the n-hexane, methylene chloride, ethyl acetate (EtOAc), and n-butanol fractions. In addition, rutin was isolated and identified from the EtOAc fraction. The 4 fractions and rutin effectively inhibited the production of reactive oxygen species, nitric oxide (NO), and interleukin-6. In addition, the mRNA expression levels of pro-inflammatory factors including nuclear factor kappa B, cyclooxygenase-2, and inducible NO synthase were down-regulated in LPS- and IFN-γ-stimulated RAW264.7 cells following treatment with the 4 fractions and rutin. The present study suggests that TB could induce anti-inflammation by regulating the expression of inflammatory mediators. PMID:26134972

  12. The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

    Directory of Open Access Journals (Sweden)

    Drenka Trivanović

    2016-01-01

    Full Text Available State of tumor microenvironment (TME is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that makes them suitable delivery vehicles for immune-stimulating factors and vectors for targeted antitumor therapy. Here, we review data regarding intrusive effects of inflammatory TME on MSCs capacity to affect tumor development through modification of their phenotype and interactions with immune system.

  13. The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

    Science.gov (United States)

    Krstić, Jelena; Djordjević, Ivana Okić; Jauković, Aleksandra

    2016-01-01

    State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that makes them suitable delivery vehicles for immune-stimulating factors and vectors for targeted antitumor therapy. Here, we review data regarding intrusive effects of inflammatory TME on MSCs capacity to affect tumor development through modification of their phenotype and interactions with immune system.

  14. Tricin, flavonoid from Njavara reduces inflammatory responses in hPBMCs by modulating the p38MAPK and PI3K/Akt pathways and prevents inflammation associated endothelial dysfunction in HUVECs.

    Science.gov (United States)

    Shalini, V; Pushpan, Chithra K; G, Sindhu; A, Jayalekshmy; A, Helen

    2016-02-01

    Previous studies revealed the potent anti-inflammatory activity of tricin, the active component of Njavara rice bran. Here, we report the involvement of specific signaling pathways in the protective effect of tricin against LPS induced inflammation in hPBMCs and the role of tricin in modulating endothelial dysfunction in LPS induced HUVECs. Pretreatment with tricin (15μM) significantly inhibited the release of TNF-α and was comparable to the specific pathway blockers like ERK inhibitor (PD98059), JNK inhibitor (SP600125) and p38 inhibitor (SB203580), whereas an increased release of TNF-α was observed in PI3K/Akt inhibitor (LY294002) treated cells. Tricin alone and combination treatment of tricin and SB203580 showed more significant inhibition of activation of COX-2 and TNF-α than that of SB203580 alone treated group. Combination treatment of tricin and LY294002 showed increased activation of COX-2 and TNF-α, proved that PI3K activation is essential for the anti-inflammatory effect of tricin. Studies conducted on HUVECs revealed the protective effect of tricin against endothelial dysfunction associated with LPS induced inflammation by inhibiting the activation of proinflammatory mediators like TNF-α, IFN-γ, MCP 1 by modulating NF-κB and MAPK signaling pathways. ELISA and flow cytometric analysis again confirmed the protection of tricin against endothelial damage, especially from the decreased activation of cell adhesion molecules like ICAM-1, VCAM-1 and E-Selectin upon tricin treatment. This work establishes the mechanism behind the potent anti-inflammatory activity of the flavonoid tricin. PMID:26514297

  15. Regulation of T cell immunity in atopic dermatitis by microbes: The Yin and Yang of cutaneous inflammation

    Directory of Open Access Journals (Sweden)

    Tilo eBiedermann

    2015-07-01

    Full Text Available Atopic dermatitis (AD is a chronic inflammatory skin disease predominantly mediated by T helper cells. While numerous adaptive immune mechanisms in AD pathophysiology have been elucidated in detail, deciphering the impact of innate immunity in AD pathogenesis has made substantial progress in recent years and is currently a fast evolving field. As innate and adaptive immunity are intimately linked cross-talks between these two branches of the immune system are critically influencing the resulting immune response and disease. Innate immune recognition of the cutaneous microbiota was identified to substantially contribute to immune homeostasis and shaping of protective adaptive immunity in the absence of inflammation. Disturbances in the composition of the skin microbiome with reduced microbial diversity and overabundance of Staphylococcus spp. have been shown to be associated with AD inflammation. Distinct S. aureus associated microbial associated molecular patterns (MAMPs binding to TLR2 heterodimers could be identified to initiate long lasting cutaneous inflammation driven by T helper cells and consecutively local immune suppression by induction of myeloid derived suppressor cells (MDSC further favoring secondary skin infections as often seen in AD patients. Moreover dissecting cellular and molecular mechanisms in cutaneous innate immune sensing in AD pathogenesis paved the way for exploiting regulatory and anti-inflammatory pathways to attenuate skin inflammation. Activation of the innate immune system by MAMPs of non-pathogenic bacteria on AD skin alleviated cutaneous inflammation. The induction of tolerogenic dendritic cells, Interleukin-10 expression and regulatory Tr1 cells were shown to mediate this beneficial effect. Thus, activation of innate immunity by MAMPs of non-pathogenic bacteria for induction of regulatory T cell phenotypes seems to be a promising strategy for treatment of inflammatory skin disorders as atopic dermatitis. These

  16. Radiosensitive Hematopoietic Cells Determine the Extent of Skin Inflammation in Experimental Epidermolysis Bullosa Acquisita.

    Science.gov (United States)

    Iwata, Hiroaki; Witte, Mareike; Samavedam, Unni Krishna S R L; Gupta, Yask; Shimizu, Atsushi; Ishiko, Akira; Schröder, Tobias; Seeger, Karsten; Dahlke, Markus; Rades, Dirk; Zillikens, Detlef; Ludwig, Ralf J

    2015-09-01

    Animal models have enhanced our understanding of the pathogenesis of autoimmune diseases. For these models, genetically identical, inbred mice have commonly been used. Different inbred mouse strains, however, show a high variability in disease manifestation. Identifying the factors that influence this disease variability could provide unrecognized insights into pathogenesis. We established a novel Ab transfer-induced model of epidermolysis bullosa acquisita (EBA), an autoimmune disease characterized by (muco)-cutaneous blistering caused by anti-type VII collagen (COL7) autoantibodies. Blistering after anti-COL7 IgG (directed against the von Willebrand factor A-like domain 2) transfer showed clear variability among inbred mouse strains, that is, severe cutaneous blistering and inflammation in C57BL/6J and absence of skin lesions in MRL/MpJ mice. The transfer of anti-COL7 IgG into irradiated, EBA-resistant MRL/MpJ mice, rescued by transplantation with bone marrow from EBA-susceptible B6.AK-H2k mice, induced blistering. To the contrary, irradiated EBA-susceptible B6.AK-H2k mice that were rescued using MRL/MpJ bone marrow were devoid of blistering. In vitro, immune complex activation of neutrophils from C57BL/6J or MRL/MpJ mice showed an impaired reactive oxygen species release from the latter, whereas no differences were observed after PMA activation. This finding was paralleled by divergent expression profiles of immune complex-activated neutrophils from either C57BL/6J or MRL/MpJ mice. Collectively, we demonstrate that radiosensitive cells determine the varying extent of skin inflammation and blistering in the end-stage effector phase of EBA. PMID:26202985

  17. Heme oxygenase-1 (HO-1 expression in prostate cancer cells modulates the oxidative response in bone cells.

    Directory of Open Access Journals (Sweden)

    Mercedes Ferrando

    Full Text Available Prostate cancer (PCa is a leading cause of death among males. It is currently estimated that inflammatory responses are linked to 15-20% of all deaths from cancer worldwide. PCa is dominated by complications arising from metastasis to the bone where the tumor cells interact with the bone microenvironment impairing the balance between bone formation and degradation. However, the molecular nature of this interaction is not completely understood. Heme oxygenase-1 (HO-1 counteracts oxidative damage and inflammation. Previous studies from our laboratory showed that HO-1 is implicated in PCa, demonstrating that endogenous HO-1 inhibits bone derived-prostate cancer cells proliferation, invasion and migration and decreases tumor growth and angiogenesis in vivo. The aim of this work was to analyze the impact of HO-1 modulated PCa cells on osteoblasts proliferation in vitro and on bone remodeling in vivo. Using a co-culture system of PC3 cells with primary mice osteoblasts (PMOs, we demonstrated that HO-1 pharmacological induction (hemin treatment abrogated the diminution of PMOs proliferation induced by PCa cells and decreased the expression of osteoclast-modulating factors in osteoblasts. No changes were detected in the expression of genes involved in osteoblasts differentiation. However, co-culture of hemin pre-treated PC3 cells (PC3 Hem with PMOs provoked an oxidative status and activated FoxO signaling in osteoblasts. The percentage of active osteoblasts positive for HO-1 increased in calvarias explants co-cultured with PC3 Hem cells. Nuclear HO-1 expression was detected in tumors generated by in vivo bone injection of HO-1 stable transfected PC3 (PC3HO-1 cells in the femur of SCID mice. These results suggest that HO-1 has the potential to modify the bone microenvironment impacting on PCa bone metastasis.

  18. A high-fish-oil diet prevents adiposity and modulates white adipose tissue inflammation pathways in mice.

    Science.gov (United States)

    Bargut, Thereza Cristina Lonzetti; Mandarim-de-Lacerda, Carlos Alberto; Aguila, Marcia Barbosa

    2015-09-01

    Fish oil improves obesity and its comorbidities, but its mechanisms of action remain unknown. We evaluate the effects of a diet rich in fish oil in white adipose tissue (WAT) inflammation pathways, renin-angiotensin system (RAS) and mitogen-activated protein kinases (MAPKs). To achieve our aims, four groups of male C57BL/6 mice were fed different diets: standard chow diet (SC; 10% energy from fat), SC+fish oil diet (SC-FO; 10% energy from fat), high-fat lard diet (HF-L; 50% energy from lard) and HF fish oil diet (HF-FO; 50% energy from fish oil). We evaluated body mass, epididymal fat pad mass, food intake and glucose tolerance. In WAT, we assessed adipocyte hypertrophy, monocyte chemotactic protein-1 immunofluorescence, and gene and protein expression of insulin signaling, inflammation, MAPKs, RAS, peroxisome proliferator-activated receptors (PPARs) and AMP-activated protein kinase (AMPK). In relation to the results, the HF-L group, as expected, showed elevated body mass and adiposity, glucose intolerance and hypertrophied adipocytes. In WAT, we found a defect in insulin signaling, infiltration of macrophages and inflammatory markers with the associated activation of MAPKs and local RAS. On the contrary, the HF-FO group did not present increased body mass, adiposity or glucose intolerance. In this group, insulin signaling, macrophage infiltration and inflammation were reduced in WAT in comparison with the HF-L group. We also observed decreases of MAPKs and local RAS and elevation of PPAR and AMPK. In summary, fish oil activates PPAR (the three isoforms) and AMPK, decreases WAT insulin resistance and inflammation, and inhibits MAPK and RAS pathways activation.

  19. Enhancement of Allergen-induced Airway Inflammation by NOX2 Deficiency

    OpenAIRE

    Won, Hee Yeon; Jang, Eun Jung; Min, Hyun Jung; Hwang, Eun Sook

    2011-01-01

    Background NADPH oxidase (NOX) modulates cell proliferation, differentiation and immune response through generation of reactive oxygen species. Particularly, NOX2 is recently reported to be important for regulating Treg cell differentiation of CD4+ T cells. Methods We employed ovalbumin-induced airway inflammation in wild-type and NOX2-deficient mice and analyzed tissue histopathology and cytokine profiles. Results We investigated whether NOX2-deficiency affects T cell-mediated airway inflamm...

  20. CD8(+) T cells mediate RAS-induced psoriasis-like skin inflammation through IFN-γ.

    Science.gov (United States)

    Gunderson, Andrew J; Mohammed, Javed; Horvath, Frank J; Podolsky, Michael A; Anderson, Cherie R; Glick, Adam B

    2013-04-01

    The RAS signaling pathway is constitutively activated in psoriatic keratinocytes. We expressed activated H-RAS(V12G) in suprabasal keratinocytes of adult mice and observed rapid development of a psoriasis-like skin phenotype characterized by basal keratinocyte hyperproliferation, acanthosis, hyperkeratosis, intraepidermal neutrophil microabscesses, and increased T helper type 1 (Th1)/Th17 and T cell type 1 (Tc1)/Tc17 skin infiltration. The majority of skin-infiltrating CD8(+) T cells coexpressed IFN-γ and IL-17A. When RAS was expressed on a Rag1-/- background, microabscess formation, inducible nitric oxide synthase expression, and keratinocyte hyperproliferation were suppressed. Depletion of CD8(+), but not CD4(+), T cells reduced cutaneous and systemic inflammation, the RAS-induced increase in cutaneous Th17 and IL-17(+) γδ T cells, and epidermal hyperproliferation to levels similar to a Rag1-/- background. Reconstitution of Rag1-/- inducible RAS mice with purified CD8(+) T cells restored microabscess formation and epidermal hyperproliferation. Neutralization of IFN-γ, but not of IL-17A, in CD8(+) T-cell-reconstituted Rag1-/- mice expressing RAS blocked CD8-mediated skin inflammation, inducible nitric oxide synthase expression, and keratinocyte hyperproliferation. These results show that CD8(+) T cells can orchestrate skin inflammation with psoriasis-like pathology in response to constitutive RAS activation in keratinocytes, and this is primarily mediated through IFN-γ. PMID:23151849

  1. Mesenchymal stem cells improve medullary inflammation and fibrosis after revascularization of swine atherosclerotic renal artery stenosis.

    Directory of Open Access Journals (Sweden)

    Behzad Ebrahimi

    Full Text Available Atherosclerotic renal artery stenosis (ARAS raises blood pressure and can reduce kidney function. Revascularization of the stenotic renal artery alone does not restore renal medullary structure and function. This study tested the hypothesis that addition of mesenchymal stem cells (MSC to percutaneous transluminal renal angioplasty (PTRA can restore stenotic-kidney medullary tubular transport function and attenuate its remodeling. Twenty-seven swine were divided into three ARAS (high-cholesterol diet and renal artery stenosis and a normal control group. Six weeks after ARAS induction, two groups were treated with PTRA alone or PTRA supplemented with adipose-tissue-derived MSC (10 × 10(6 cells intra-renal. Multi-detector computed tomography and blood-oxygenation-level-dependent (BOLD MRI studies were performed 4 weeks later to assess kidney hemodynamics and function, and tissue collected a few days later for histology and micro-CT imaging. PTRA effectively decreased blood pressure, yet medullary vascular density remained low. Addition of MSC improved medullary vascularization in ARAS+PTRA+MSC and increased angiogenic signaling, including protein expression of vascular endothelial growth-factor, its receptor (FLK-1, and hypoxia-inducible factor-1α. ARAS+PTRA+MSC also showed attenuated inflammation, although oxidative-stress remained elevated. BOLD-MRI indicated that MSC normalized oxygen-dependent tubular response to furosemide (-4.3 ± 0.9, -0.1 ± 0.4, -1.6 ± 0.9 and -3.6 ± 1.0 s(-1 in Normal, ARAS, ARAS+PTRA and ARAS+PTRA+MSC, respectively, p<0.05, which correlated with a decrease in medullary tubular injury score (R(2 = 0.33, p = 0.02. Therefore, adjunctive MSC delivery in addition to PTRA reduces inflammation, fibrogenesis and vascular remodeling, and restores oxygen-dependent tubular function in the stenotic-kidney medulla, although additional interventions might be required to reduce oxidative-stress. This study supports development of

  2. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation

    DEFF Research Database (Denmark)

    Nassini, Romina; Pedretti, Pamela; Moretto, Nadia;

    2012-01-01

    inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express...... activation orchestrates an additional inflammatory response which is not neurogenic. This finding suggests that non-neuronal TRPA1 in the airways is functional and potentially capable of contributing to inflammatory airway diseases....... functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells...

  3. Transfer of in vivo primed transgenic T cells supports allergic lung inflammation and FIZZ1 and Ym1 production in an IL-4Rα and STAT6 dependent manner

    Directory of Open Access Journals (Sweden)

    Keegan Achsah D

    2011-10-01

    Full Text Available Abstract Background CD4+ T helper type 2 (TH2 cells, their cytokines IL-4, IL-5 and IL-13 and the transcription factor STAT6 are known to regulate various features of asthma including lung inflammation, mucus production and airway hyperreactivity and also drive alternative activation of macrophages (AAM. However, the precise roles played by the IL-4/IL-13 receptors and STAT6 in inducing AAM protein expression and modulating specific features of airway inflammation are still unclear. Since TH2 differentiation and activation plays a pivotal role in this disease, we explored the possibility of developing an asthma model in mice using T cells that were differentiated in vivo. Results In this study, we monitored the activation and proliferation status of adoptively transferred allergen-specific naïve or in vivo primed CD4+ T cells. We found that both the naïve and in vivo primed T cells expressed similar levels of CD44 and IL-4. However, in vivo primed T cells underwent reduced proliferation in a lymphopenic environment when compared to naïve T cells. We then used these in vivo generated effector T cells in an asthma model. Although there was reduced inflammation in mice lacking IL-4Rα or STAT6, significant amounts of eosinophils were still present in the BAL and lung tissue. Moreover, specific AAM proteins YM1 and FIZZ1 were expressed by epithelial cells, while macrophages expressed only YM1 in RAG2-/- mice. We further show that FIZZ1 and YM1 protein expression in the lung was completely dependent on signaling through the IL-4Rα and STAT6. Consistent with the enhanced inflammation and AAM protein expression, there was a significant increase in collagen deposition and smooth muscle thickening in RAG2-/- mice compared to mice deficient in IL-4Rα or STAT6. Conclusions These results establish that transfer of in vivo primed CD4+ T cells can induce allergic lung inflammation. Furthermore, while IL-4/IL-13 signaling through IL-4Rα and STAT6 is

  4. Mechanisms of Innate Lymphoid Cell and Natural Killer T Cell Activation during Mucosal Inflammation

    OpenAIRE

    David Nau; Nora Altmayer; Jochen Mattner

    2014-01-01

    Mucosal surfaces in the airways and the gastrointestinal tract are critical for the interactions of the host with its environment. Due to their abundance at mucosal tissue sites and their powerful immunomodulatory capacities, the role of innate lymphoid cells (ILCs) and natural killer T (NKT) cells in the maintenance of mucosal tolerance has recently moved into the focus of attention. While NKT cells as well as ILCs utilize distinct transcription factors for their development and lineage dive...

  5. Study of the betulin enriched birch bark extracts effects on human carcinoma cells and ear inflammation

    Directory of Open Access Journals (Sweden)

    Dehelean Cristina A

    2012-11-01

    Full Text Available Abstract Background Pentacyclic triterpenes, mainly betulin and betulinic acid, are valuable anticancer agents found in the bark of birch tree. This study evaluates birch bark extracts for the active principles composition. Results New improved extraction methods were applied on the bark of Betula pendula in order to reach the maximum content in active principles. Extracts were analyzed by HPLC-MS, Raman, SERS and 13C NMR spectroscopy which revealed a very high yield of betulin (over 90%. Growth inhibiting effects were measured in vitro on four malignant human cell lines: A431 (skin epidermoid carcinoma, A2780 (ovarian carcinoma, HeLa (cervix adenocarcinoma and MCF7 (breast adenocarcinoma, by means of MTT assay. All of the prepared bark extracts exerted a pronounced antiproliferative effect against human cancer cell lines. In vivo studies involved the anti-inflammatory effect of birch extracts on TPA-induced model of inflammation in mice. Conclusions The research revealed the efficacy of the extraction procedures as well as the antiproliferative and anti-inflammatory effects of birch extracts.

  6. Magnetic ferroferric oxide nanoparticles induce vascular endothelial cell dysfunction and inflammation by disturbing autophagy.

    Science.gov (United States)

    Zhang, Lu; Wang, XueQin; Miao, YiMing; Chen, ZhiQiang; Qiang, PengFei; Cui, LiuQing; Jing, Hongjuan; Guo, YuQi

    2016-03-01

    Despite the considerable use of magnetic ferroferric oxide nanoparticles (Fe3O4NPs) worldwide, their safety is still an important topic of debate. In the present study, we detected the toxicity and biological behavior of bare-Fe3O4NPs (B-Fe3O4NPs) on human umbilical vascular endothelial cells (HUVECs). Our results showed that B-Fe3O4NPs did not induce cell death within 24h even at concentrations up to 400 μg/ml. The level of nitric oxide (NO) and the activity of endothelial NO synthase (eNOS) were decreased after exposure to B-Fe3O4NPs, whereas the levels of proinflammatory cytokines were elevated. Importantly, B-Fe3O4NPs increased the accumulation of autophagosomes and LC3-II in HUVECs through both autophagy induction and the blockade of autophagy flux. The levels of Beclin 1 and VPS34, but not phosphorylated mTOR, were increased in the B-Fe3O4NP-treated HUVECs. Suppression of autophagy induction or stimulation of autophagy flux, at least partially, attenuated the B-Fe3O4NP-induced HUVEC dysfunction. Additionally, enhanced autophagic activity might be linked to the B-Fe3O4NP-induced production of proinflammatory cytokines. Taken together, these results demonstrated that B-Fe3O4NPs disturb the process of autophagy in HUVECs, and eventually lead to endothelial dysfunction and inflammation.

  7. Data on importance of hematopoietic cell derived Lipocalin 2 against gut inflammation.

    Science.gov (United States)

    Saha, Piu; Singh, Vishal; Xiao, Xia; Yeoh, Beng San; Vijay-Kumar, Matam

    2016-09-01

    The data herein is related to the research article entitled "Microbiota-inducible innate immune siderophore binding protein Lipocalin 2 is critical for intestinal homeostasis" (Singh et al., 2016) [1]. In the present article, we monitored dextran sodium sulfate (DSS)-induced colitis development upon Lipocalin 2 (Lcn2) neutralization, and examined the survival of Lcn2 deficient (Lcn2KO) mice and their WT littermates upon DSS challenge. To dissect the relative contribution of immune and non-immune cells-derived Lcn2 in mediating protection against gut inflammation, we generated respective bone marrow chimera and evaluated their susceptibility to IL-10 receptor neutralization-induced chronic colitis. Neutralization of Lcn2 in WT mice resulted in exacerbated DSS-induced colitis. Notably, mice lacking Lcn2 exhibited 100% mortality whereas only 20% mortality was observed in WT mice upon DSS challenge. Further, data from bone marrow chimera showed that immune cell-derived Lcn2 is the major contributor in conferring protection against colitis. PMID:27500193

  8. Niche-modulated and niche-modulating genes in bone marrow cells

    International Nuclear Information System (INIS)

    Bone marrow (BM) cells depend on their niche for growth and survival. However, the genes modulated by niche stimuli have not been discriminated yet. For this purpose, we investigated BM aspirations from patients with various hematological malignancies. Each aspirate was fractionated, and the various samples were fixed at different time points and analyzed by microarray. Identification of niche-modulated genes relied on sustained change in expression following loss of niche regulation. Compared with the reference (‘authentic') samples, which were fixed immediately following aspiration, the BM samples fixed after longer stay out-of-niche acquired numerous changes in gene-expression profile (GEP). The overall genes modulated included a common subset of functionally diverse genes displaying prompt and sustained ‘switch' in expression irrespective of the tumor type. Interestingly, the ‘switch' in GEP was reversible and turned ‘off-and-on' again in culture conditions, resuming cell–cell–matrix contact versus respread into suspension, respectively. Moreover, the resuming of contact prolonged the survival of tumor cells out-of-niche, and the regression of the ‘contactless switch' was followed by induction of a new set of genes, this time mainly encoding extracellular proteins including angiogenic factors and extracellular matrix proteins. Our data set, being unique in authentic expression design, uncovered niche-modulated and niche-modulating genes capable of controlling homing, expansion and angiogenesis

  9. Mechanisms of Innate Lymphoid Cell and Natural Killer T Cell Activation during Mucosal Inflammation

    Directory of Open Access Journals (Sweden)

    David Nau

    2014-01-01

    Full Text Available Mucosal surfaces in the airways and the gastrointestinal tract are critical for the interactions of the host with its environment. Due to their abundance at mucosal tissue sites and their powerful immunomodulatory capacities, the role of innate lymphoid cells (ILCs and natural killer T (NKT cells in the maintenance of mucosal tolerance has recently moved into the focus of attention. While NKT cells as well as ILCs utilize distinct transcription factors for their development and lineage diversification, both cell populations can be further divided into three polarized subpopulations reflecting the distinction into Th1, Th2, and Th17 cells in the adaptive immune system. While bystander activation through cytokines mediates the induction of ILC and NKT cell responses, NKT cells become activated also through the engagement of their canonical T cell receptors (TCRs by (glycolipid antigens (cognate recognition presented by the atypical MHC I like molecule CD1d on antigen presenting cells (APCs. As both innate lymphocyte populations influence inflammatory responses due to the explosive release of copious amounts of different cytokines, they might represent interesting targets for clinical intervention. Thus, we will provide an outlook on pathways that might be interesting to evaluate in this context.

  10. Role of mast cell-derived mediators for leukocyte/endothelium-interactions and microvascular mechanisms in inflammation and in anaphylaxis.

    OpenAIRE

    Guo, Yancai

    2003-01-01

    The overall objective of this thesis was to study the roles of mast cell-derived mediators for leukocyte/endothelium interactions and microvascular mechanisms in inflammation and in anaphylaxis, using mast cell-deficient Ws/Ws rats and their wild-type +/+ littermates. The efflux of endogenous histamine and edema formation evoked by subplantar injection of compound 48/80 in rat hindpaws was dose-dependent in +/+ rats, and was essentially lacking in Ws/Ws rats. These findings...

  11. Effects of bone marrow mononuclear cells from healthy or ovalbumin-induced lung inflammation donors on recipient allergic asthma mice

    OpenAIRE

    Abreu, Soraia C.; Antunes, Mariana A.; Mendonça, Lucas; Branco, Vivian C; de Melo, Elga Bandeira; Olsen, Priscilla C.; Diaz, Bruno L.; Weiss, Daniel J; Paredes, Bruno D; Xisto, Debora G.; Morales, Marcelo M; Rocco, Patricia RM

    2014-01-01

    Introduction Asthma is characterized by a chronic inflammatory process which may lead to several changes in bone marrow cell composition. We hypothesized that bone marrow mononuclear cells (BMMCs) obtained from ovalbumin (OVA)-induced lung inflammation mice may promote different effects compared to BMMCs from healthy donors in a model of allergic asthma. Methods C57BL/6 mice were randomly assigned to two groups. In the OVA group, mice were sensitized and challenged with ovalbumin, while healt...

  12. Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation.

    Directory of Open Access Journals (Sweden)

    Ailan Zhang

    Full Text Available BACKGROUND: Acute lung injury (ALI is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation. METHODS: Adult male Sprague-Dawley rats received orthotopic autologous liver transplantation (OALT and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α, interleukin (IL-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB p65 translocation was assessed by Western blot. RESULTS: The rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI. CONCLUSIONS: Mast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.

  13. Th17 Responses in Chronic Allergic Airway Inflammation Abrogate Regulatory T cell-mediated Tolerance and Contribute to Airway Remodeling

    OpenAIRE

    Zhao, Jingyue; Lloyd, Clare M.; Noble, Alistair

    2012-01-01

    The role of Th17 responses in airway remodeling in asthma is currently unknown. We demonstrate that both parenteral and mucosal allergen sensitization followed by allergen inhalation leads to Th17-biased lung immune responses. Unlike Th17 cells generated in vitro, lung Th17 cells did not produce TNF-α or IL-22. Eosinophilia predominated in acute inflammation while neutrophilia and IL-17 increased in chronic disease. Allergen-induced tolerance involved Foxp3, Helios and GARP expressing regulat...

  14. Role of T cell TGF beta signaling in intestinal cytokine responses and helminthic immune modulation

    Science.gov (United States)

    Colonization with helminthic parasites down-regulates inflammation in murine colitis and improves activity scores in human inflammatory bowel disease. Helminths induce mucosal regulatory T cells, which are important for intestinal immunologic homeostasis. Regulatory T cell function involves cytoki...

  15. Schistosoma mansoni-mediated suppression of allergic airway inflammation requires patency and Foxp3+ Treg cells.

    Directory of Open Access Journals (Sweden)

    Laura E Layland

    Full Text Available The continual rise of asthma in industrialised countries stands in strong contrast to the situation in developing lands. According to the modified Hygiene Hypothesis, helminths play a major role in suppressing bystander immune responses to allergens, and both epidemiological and experimental studies suggest that the tropical parasitic trematode Schistosoma mansoni elicits such effects. The focus of this study was to investigate which developmental stages of schistosome infection confer suppression of allergic airway inflammation (AAI using ovalbumin (OVA as a model allergen. Moreover, we assessed the functional role and localization of infection-induced CD4(+Foxp3(+ regulatory T cells (Treg in mediating such suppressive effects. Therefore, AAI was elicited using OVA/adjuvant sensitizations with subsequent OVA aerosolic challenge and was induced during various stages of infection, as well as after successful anti-helminthic treatment with praziquantel. The role of Treg was determined by specifically depleting Treg in a genetically modified mouse model (DEREG during schistosome infection. Alterations in AAI were determined by cell infiltration levels into the bronchial system, OVA-specific IgE and Th2 type responses, airway hyper-sensitivity and lung pathology. Our results demonstrate that schistosome infection leads to a suppression of OVA-induced AAI when mice are challenged during the patent phase of infection: production of eggs by fecund female worms. Moreover, this ameliorating effect does not persist after anti-helminthic treatment, and depletion of Treg reverts suppression, resulting in aggravated AAI responses. This is most likely due to a delayed reconstitution of Treg in infected-depleted animals which have strong ongoing immune responses. In summary, we conclude that schistosome-mediated suppression of AAI requires the presence of viable eggs and infection-driven Treg cells. These data provide evidence that helminth derived products

  16. Divergent neuroendocrine responses to localised and systemic inflammation

    OpenAIRE

    Lukewich, Mark K.; Rogers, Richard C.; Lomax, Alan E.

    2014-01-01

    The sympathetic nervous system (SNS) is part of an integrative network that functions to restore homeostasis following injury and infection. The SNS can provide negative feedback control over inflammation through the secretion of catecholamines from postganglionic sympathetic neurons and adrenal chromaffin cells (ACCs). Central autonomic structures receive information regarding the inflammatory status of the body and reflexively modulate SNS activity. However, inflammation and infection can a...

  17. Mast Cells Modulate Acute Toxoplasmosis in Murine Models

    OpenAIRE

    Bo Huang; Shiguang Huang; Ying Chen; Huanqin Zheng; Jilong Shen; Zhao-Rong Lun; Yong Wang; Kasper, Lloyd H.; Fangli Lu

    2013-01-01

    The role of mast cells (MCs) in Toxoplasma gondii infection is poorly known. Kunming outbred mice were infected intraperitoneally with RH strain T. gondii, either treated with compound 48/80 (C48/80, MC activator) or disodium cromoglycate (DSCG, MC inhibitor). Compared with infected controls, infected mice treated with C48/80 exhibited significantly increased inflammation in the liver (P < 0.01), spleen (P < 0.05), and mesentery (P < 0.05) tissues, higher parasite burden in the peritoneal lav...

  18. Solar cell junction temperature measurement of PV module

    KAUST Repository

    Huang, B.J.

    2011-02-01

    The present study develops a simple non-destructive method to measure the solar cell junction temperature of PV module. The PV module was put in the environmental chamber with precise temperature control to keep the solar PV module as well as the cell junction in thermal equilibrium with the chamber. The open-circuit voltage of PV module Voc is then measured using a short pulse of solar irradiation provided by a solar simulator. Repeating the measurements at different environment temperature (40-80°C) and solar irradiation S (200-1000W/m2), the correlation between the open-circuit voltage Voc, the junction temperature Tj, and solar irradiation S is derived.The fundamental correlation of the PV module is utilized for on-site monitoring of solar cell junction temperature using the measured Voc and S at a short time instant with open circuit. The junction temperature Tj is then determined using the measured S and Voc through the fundamental correlation. The outdoor test results show that the junction temperature measured using the present method, Tjo, is more accurate. The maximum error using the average surface temperature Tave as the junction temperature is 4.8 °C underestimation; while the maximum error using the present method is 1.3 °C underestimation. © 2010 Elsevier Ltd.

  19. Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells

    Science.gov (United States)

    Lin, Hwai-Jeng; Hsu, Fang-Yu; Chen, Wei-Wei; Lee, Che-Hsin; Lin, Ying-Ju; Chen, Yi-Ywan M.; Chen, Chih-Jung; Huang, Mei-Zi; Kao, Min-Chuan; Chen, Yu-An; Lai, Hsin-Chih; Lai, Chih-Ho

    2016-01-01

    Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases. PMID:27667993

  20. Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells.

    Science.gov (United States)

    Lin, Hwai-Jeng; Hsu, Fang-Yu; Chen, Wei-Wei; Lee, Che-Hsin; Lin, Ying-Ju; Chen, Yi-Ywan M; Chen, Chih-Jung; Huang, Mei-Zi; Kao, Min-Chuan; Chen, Yu-An; Lai, Hsin-Chih; Lai, Chih-Ho

    2016-01-01

    Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases. PMID:27667993

  1. 1,8-cineole (eucalyptol) mitigates inflammation in amyloid Beta toxicated PC12 cells: relevance to Alzheimer's disease.

    Science.gov (United States)

    Khan, Andleeb; Vaibhav, Kumar; Javed, Hayate; Tabassum, Rizwana; Ahmed, Md Ejaz; Khan, Mohd Moshahid; Khan, M Badruzzaman; Shrivastava, Pallavi; Islam, Farah; Siddiqui, M Saeed; Safhi, M M; Islam, Fakhrul

    2014-02-01

    Inflammatory process has a fundamental role in the pathogenesis of Alzheimer's disease and insoluble amyloid beta deposits and neurofibrillary tangles provide the obvious stimuli for inflammation. The present study demonstrate the effect of pretreatment of 1,8-cineole (Cin) on inflammation induced by Aβ(25-35) in differentiated PC12 cells. The cells were treated with Cin at different doses for 24 h and then replaced by media containing Aβ(25-35) for another 24 h. The cell viability was decreased in Aβ(25-35) treated cells which was significantly restored by Cin pretreatment. Cin successfully reduced the mitochondrial membrane potential, ROS and NO levels in Aβ(25-35) treated cells. Cin also lowered the levels of proinflammatory cytokines TNF-α, IL-1β and IL-6 in Aβ(25-35) treated cells. Moreover, Cin also succeeded in lowering the expression of NOS-2, COX-2 and NF-κB. This study suggests the protective effects of Cin on inflammation and provides additional evidence for its potential beneficial use in therapy as an anti-inflammatory agent in neurodegenerative disease.

  2. EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sung Gu [Superfund Research Program, University of Kentucky, Lexington, KY 40536 (United States); Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536 (United States); Han, Seong-Su [Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA 52242 (United States); Toborek, Michal [Department of Neurosurgery, University of Kentucky, Lexington, KY 40536 (United States); Hennig, Bernhard, E-mail: bhennig@uky.edu [Superfund Research Program, University of Kentucky, Lexington, KY 40536 (United States); Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536 (United States)

    2012-06-01

    Tea flavonoids such as epigallocatechin gallate (EGCG) protect against vascular diseases such as atherosclerosis via their antioxidant and anti-inflammatory functions. Persistent and widespread environmental pollutants, including polychlorinated biphenyls (PCB), can induce oxidative stress and inflammation in vascular endothelial cells. Even though PCBs are no longer produced, they are still detected in human blood and tissues and thus considered a risk for vascular dysfunction. We hypothesized that EGCG can protect endothelial cells against PCB-induced cell damage via its antioxidant and anti-inflammatory properties. To test this hypothesis, primary vascular endothelial cells were pretreated with EGCG, followed by exposure to the coplanar PCB 126. Exposure to PCB 126 significantly increased cytochrome P450 1A1 (Cyp1A1) mRNA and protein expression and superoxide production, events which were significantly attenuated following pretreatment with EGCG. Similarly, EGCG also reduced DNA binding of NF-κB and downstream expression of inflammatory markers such as monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) after PCB exposure. Furthermore, EGCG decreased endogenous or base-line levels of Cyp1A1, MCP-1 and VCAM-1 in endothelial cells. Most of all, treatment of EGCG upregulated expression of NF-E2-related factor 2 (Nrf2)-controlled antioxidant genes, including glutathione S transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), in a dose-dependent manner. In contrast, silencing of Nrf2 increased Cyp1A1, MCP-1 and VCAM-1 and decreased GST and NQO1 expression, respectively. These data suggest that EGCG can inhibit AhR regulated genes and induce Nrf2-regulated antioxidant enzymes, thus providing protection against PCB-induced inflammatory responses in endothelial cells. -- Highlights: ► PCBs cause endothelial inflammation and subsequent atherosclerosis. ► Nutrition can modulate toxicity by environmental pollutants. ► We

  3. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation.

    Directory of Open Access Journals (Sweden)

    Romina Nassini

    Full Text Available BACKGROUND: The transient receptor potential ankyrin 1 (TRPA1 channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1. METHODOLOGY/PRINCIPAL FINDINGS: By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells and fibroblasts, acrolein and CS extract evoked IL-8 release, a response selectively reduced by TRPA1 antagonists. Capsaicin, agonist of the transient receptor potential vanilloid 1 (TRPV1, a channel co-expressed with TRPA1 by airway sensory nerves, and acrolein or CS (TRPA1 agonists, or the neuropeptide substance P (SP, which is released from sensory nerve terminals by capsaicin, acrolein or CS, produced neurogenic inflammation in mouse airways. However, only acrolein and CS, but not capsaicin or SP, released the keratinocyte chemoattractant (CXCL-1/KC, IL-8 analogue in bronchoalveolar lavage (BAL fluid of wild-type mice. This effect of TRPA1 agonists was attenuated by TRPA1 antagonism or in TRPA1-deficient mice, but not by pharmacological ablation of sensory nerves. CONCLUSIONS: Our results demonstrate that, although either TRPV1 or TRPA1 activation causes airway neurogenic inflammation, solely TRPA1 activation orchestrates an additional inflammatory response which is not neurogenic. This finding suggests

  4. Equine herpesvirus type 1 modulates inflammatory host immune response genes in equine endothelial cells.

    Science.gov (United States)

    Johnstone, Stephanie; Barsova, Jekaterina; Campos, Isabel; Frampton, Arthur R

    2016-08-30

    Equine herpesvirus myeloencephalopathy (EHM), a disease caused by equine herpesvirus type 1 (EHV-1), is characterized by severe inflammation, thrombosis, and hypoxia in central nervous system (CNS) endothelial cells, which can result in a spectrum of clinical signs including urinary incontinence, ataxia, and paralysis. Strains of EHV-1 that contain a single point mutation within the viral DNA polymerase (nucleotide A2254>G2254: amino acid N752→D752) are isolated from EHM afflicted horses at higher frequencies than EHV-1 strains that do not harbor this mutation. Due to the correlation between the DNA Pol mutation and EHM disease, EHV-1 strains that contain the mutation have been designated as neurologic. In this study, we measured virus replication, cell to cell spread efficacy, and host inflammatory responses in equine endothelial cells infected with 12 different strains of EHV-1. Two strains, T953 (Ohio 2003) (neurologic) and Kentucky A (KyA) (non-neurologic), have well described disease phenotypes while the remaining strains used in this study are classified as neurologic or non-neurologic based solely on the presence or absence of the DNA pol mutation, respectively. Results show that the neurologic strains do not replicate better or spread more efficiently in endothelial cells. Also, the majority of the host inflammatory genes were modulated similarly regardless of EHV-1 genotype. Analyses of host gene expression showed that a subset of pro-inflammatory cytokines, including the CXCR3 ligands CXCL9, CXCL10, and CXCL11, as well as CCL5, IL-6 and TNF-α were consistently up-regulated in endothelial cells infected with each EHV-1 strain. The identification of specific pro-inflammatory cytokines in endothelial cells that are modulated by EHV-1 provides further insight into the factors that contribute to the immunopathology observed after infection and may also reveal new targets for disease intervention. PMID:27527764

  5. Advances in targeting cell surface signalling molecules for immune modulation

    Science.gov (United States)

    Yao, Sheng; Zhu, Yuwen; Chen, Lieping

    2013-01-01

    The past decade has witnessed a surge in the development of immunomodulatory approaches to combat a broad range of human diseases, including cancer, viral infections, autoimmunity and inflammation as well as in the prevention of transplant rejection. Immunomodulatory approaches mostly involve the use of monoclonal antibodies or recombinant fusion proteins that target cell surface signalling molecules on immune cells to drive immune responses towards the desired direction. Advances in our understanding of the human immune system, along with valuable lessons learned from the first generation of therapeutic biologics, are aiding the design of the next generation of immunomodulatory biologics with better therapeutic efficacy, minimized adverse effects and long-lasting clinical benefit. The recent encouraging results from antibodies targeting programmed cell death protein 1 (PD1) and B7 homolog 1 (B7H1; also known as PDL1) for the treatment of various advanced human cancers show that immunomodulatory therapy has come of age. PMID:23370250

  6. Mesenchymal stem cell-conditioned medium prevents radiation-induced liver injury by inhibiting inflammation and protecting sinusoidal endothelial cells

    International Nuclear Information System (INIS)

    Current management of radiation-induced liver injury is limited. Sinusoidal endothelial cell (SEC) apoptosis and inflammation are considered to be initiating events in hepatic damage. We hypothesized that mesenchymal stem cells (MSCs) possess anti-apoptotic and anti-inflammatory actions during hepatic irradiation, acting via paracrine mechanisms. This study aims to examine whether MSC-derived bioactive components are protective against radiation-induced liver injury in rats. MSC-conditioned medium (MSC-CM) was generated from rat bone marrow–derived MSCs. The effect of MSC-CM on the viability of irradiated SECs was examined by flow cytometric analysis. Activation of the Akt and ERK pathways was analyzed by western blot. MSC-CM was also delivered to Sprague–Dawley rats immediately before receiving liver irradiation, followed by testing for pathological features, changes in serum hyaluronic acid, ALT, and inflammatory cytokine levels, and liver cell apoptosis. MSC-CM enhanced the viability of irradiated SECs in vitro and induced Akt and ERK phosphorylation in these cells. Infusion of MSC-CM immediately before liver irradiation provided a significant anti-apoptotic effect on SECs and improved the histopathological features of injury in the irradiated liver. MSC-CM also reduced the secretion and expression of inflammatory cytokines and increased the expression of anti-inflammatory cytokines. MSC-derived bioactive components could be a novel therapeutic approach for treating radiation-induced liver injury. (author)

  7. Target cell-specific modulation of neuronal activity by astrocytes

    OpenAIRE

    Kozlov, A. S.; Angulo, M. C.; Audinat, E.; Charpak, S

    2006-01-01

    Interaction between astrocytes and neurons enriches the behavior of brain circuits. By releasing glutamate and ATP, astrocytes can directly excite neurons and modulate synaptic transmission. In the rat olfactory bulb, we demonstrate that the release of GABA by astrocytes causes long-lasting and synchronous inhibition of mitral and granule cells. In addition, astrocytes release glutamate, leading to a selective activation of granule-cell NMDA receptors. Thus, by releasing excitatory and inhibi...

  8. Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Janel E. Le Belle

    2014-11-01

    Full Text Available A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  9. Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells.

    Science.gov (United States)

    Le Belle, Janel E; Sperry, Jantzen; Ngo, Amy; Ghochani, Yasmin; Laks, Dan R; López-Aranda, Manuel; Silva, Alcino J; Kornblum, Harley I

    2014-11-11

    A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX)-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  10. Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Soendergaard, Christoffer; Joergensen, Steffen;

    2016-01-01

    , proliferation, differentiation, as well as tumor invasion and intestinal inflammation, and its expression is enhanced by TNF-α in a NF-κB-dependent regulation of the recently identified LAMC2 enhancer. The aim was to determine whether CDX2 is involved in the basal regulation of LAMC2 in epithelial cells...... human epithelial cells. Immunohistochemical staining and quantitative reverse-transcription polymerase chain reaction analyses were used to measure the expression of CDX2 and LAMC2 in colonic biopsies from healthy controls and patients with UC. These data indicate that CDX2 directly regulates LAMC2 gene...... expression through interaction with elements in the LAMC2 promoter region. We further revealed an inverse effect of inflammation on CDX2 and LAMC2. The data presented provide a novel insight into how CDX2 is implicated in the transcriptional regulation of LAMC2 in intestinal epithelial cells, a function...

  11. Inhibitory effect of putranjivain A on allergic inflammation through suppression of mast cell activation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hui-Hun; Park, Seung-Bin; Lee, Soyoung [CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Kwon, Taeg Kyu [Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701 (Korea, Republic of); Shin, Tae-Yong [College of Pharmacy, Woosuk University, Jeonju 565-701 (Korea, Republic of); Park, Pil-Hoon; Lee, Seung-Ho [College of Pharmacy, Youngnam University, Kyungsan 712-749 (Korea, Republic of); Kim, Sang-Hyun, E-mail: shkim72@knu.ac.kr [CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of)

    2014-02-01

    A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Putranjivain A (PJA), member of ellagitannin, is known to possess beneficial effects including anti-cancer and anti-viral activities. The aim of the present study was to elucidate whether PJA modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. The study was performed in anaphylaxis mouse model and cultured mast cells. PJA inhibited the expression of pro-inflammatory cytokines in immunoglobulin E-stimulated mast cells. PJA reduced this expression by inhibiting nuclear factor (NF)-κB and nuclear factor of activated T cell. The oral administration of PJA reduced systemic and cutaneous anaphylaxis, the release of serum histamine, and the expression of the histamine H{sub 1} receptor. In addition, PJA attenuated the activation of mast cells. PJA inhibited the release of histamine from various types of mast cells by the suppression of intracellular calcium. The inhibitory activity of PJA on the allergic reaction was similar to that of disodium cromoglycate, a known anti-allergic drug. These results suggest that PJA can facilitate the prevention or treatment of allergic inflammatory diseases mediated by mast cells. - Highlights: • PJA reduced the degranulation of mast cells. • PJA inhibited the production of inflammatory cytokines. • The effect of PJA on allergic reaction was comparable to the DSCG. • PJA might be a candidate for the treatment of allergic inflammatory diseases.

  12. Matrix Stiffness Modulates Proliferation, Chemotherapeutic Response and Dormancy in Hepatocellular Carcinoma Cells

    Science.gov (United States)

    Schrader, Jörg; Gordon-Walker, Timothy T; Aucott, Rebecca L; van Deemter, Mariëlle; Quaas, Alexander; Walsh, Shaun; Benten, Daniel; Forbes, Stuart J; Wells, Rebecca G; Iredale, John P

    2010-01-01

    There is increasing evidence that the physical environment is a critical mediator of tumor behavior. Hepatocellular carcinoma (HCC) develops within an altered biomechanical environment and increasing matrix stiffness is a strong predictor of HCC development. The aim of this study was to establish whether changes in matrix stiffness, which are characteristic of inflammation and fibrosis, regulate HCC cell proliferation and chemotherapeutic response. Using an in vitro system of “mechanically-tunable” matrix-coated polyacrylamide gels, matrix stiffness was modeled across a pathophysiologically-relevant range, corresponding to values encountered in normal and fibrotic livers. Results Increasing matrix stiffness was found to promote HCC cell proliferation. The proliferative index (assessed by Ki67 staining) of Huh7 and HepG2 cells was 2.7-fold and 12.2-fold higher, respectively, when the cells were cultured on stiff (12kPa) versus soft (1kPa) supports. This was associated with stiffness-dependent regulation of basal and HGF-stimulated mitogenic signaling through extracellular regulated kinase (ERK), protein kinase B (PKB/Akt) and signal transducer and activator of transcription 3 (STAT3). β1-integrin and focal adhesion kinase (FAK) were found to modulate stiffness-dependent HCC cell proliferation. Following treatment with cisplatin, we observed reduced apoptosis in HCC cells cultured on a stiff versus soft (physiological) supports. Interestingly, however, surviving cells from soft supports had significantly higher clonogenic capacity than surviving cells from a stiff microenvironment. This was associated with enhanced expression of cancer stem cell markers, including CD44, CD133, c-kit, CXCR4, octamer-4 (OCT4) and NANOG. Conclusion Increasing matrix stiffness promotes proliferation and chemotherapeutic resistance, whereas a soft environment induces reversible cellular dormancy and stem cell characteristics in HCC. This has implications for both the treatment of

  13. Phosphatidylinositol 3 kinase modulation of trophoblast cell differentiation

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    Kent Lindsey N

    2010-09-01

    Full Text Available Abstract Background The trophoblast lineage arises as the first differentiation event during embryogenesis. Trophoblast giant cells are one of several end-stage products of trophoblast cell differentiation in rodents. These cells are located at the maternal-fetal interface and are capable of invasive and endocrine functions, which are necessary for successful pregnancy. Rcho-1 trophoblast stem cells can be effectively used as a model for investigating trophoblast cell differentiation. In this report, we evaluated the role of the phosphatidylinositol 3-kinase (PI3K signaling pathway in the regulation of trophoblast cell differentiation. Transcript profiles from trophoblast stem cells, differentiated trophoblast cells, and differentiated trophoblast cells following disruption of PI3K signaling were generated and characterized. Results Prominent changes in gene expression accompanied the differentiation of trophoblast stem cells. PI3K modulated the expression of a subset of trophoblast cell differentiation-dependent genes. Among the PI3K-responsive genes were those encoding proteins contributing to the invasive and endocrine phenotypes of trophoblast giant cells. Conclusions Genes have been identified with differential expression patterns associated with trophoblast stem cells and trophoblast cell differentiation; a subset of these genes are regulated by PI3K signaling, including those impacting the differentiated trophoblast giant cell phenotype.

  14. A possible link between loading, inflammation and healing: Immune cell populations during tendon healing in the rat.

    Science.gov (United States)

    Blomgran, Parmis; Blomgran, Robert; Ernerudh, Jan; Aspenberg, Per

    2016-01-01

    Loading influences tendon healing, and so does inflammation. We hypothesized that the two are connected. 48 rats underwent Achilles tendon transection. Half of the rats received Botox injections into calf muscles to reduce mechanical loading. Cells from the regenerating tissue were analyzed by flow cytometry. In the loaded group, the regenerating tissue contained 83% leukocytes (CD45(+)) day 1, and 23% day 10. The M1/M2 macrophage ratio (CCR7/CD206) peaked at day 3, while T helper (CD3(+)CD4(+)) and Treg cells (CD25(+) Foxp3(+)) increased over time. With Botox, markers associated with down-regulation of inflammation were more common day 5 (CD163, CD206, CD25, Foxp3), and M1 or M2 macrophages and Treg cells were virtually absent day 10, while still present with full loading. The primary variable, CCR7/CD206 ratio day 5, was higher with full loading (p = 0.001) and the Treg cell fraction was lower (p < 0.001). Free cage activity loading is known to increase size and strength of the tendon in this model compared to Botox. Loading now appeared to delay the switch to an M2 type of inflammation with more Treg cells. It seems a prolonged M1 phase due to loading might make the tendon regenerate bigger. PMID:27405922

  15. Therapeutic expansion of CD4+FoxP3+ regulatory T cells limits allergic airway inflammation during pulmonary fungal infection.

    Science.gov (United States)

    Schulze, Bianca; Piehler, Daniel; Eschke, Maria; Heyen, Laura; Protschka, Martina; Köhler, Gabriele; Alber, Gottfried

    2016-06-01

    Allergic asthma can be frequently caused and exacerbated by sensitization to ubiquitous fungal allergens associated with pulmonary mucus production, airway hyperresponsiveness and bronchial constriction, resulting in a complex disease that is often difficult to treat. Fungal infections are frequently complicated by the development of a type 2 immune response that prevents successful elimination of the fungal pathogen. Furthermore, production of type 2 cytokines triggers allergic airway inflammation. Following intranasal infection of BALB/c mice with the fungusCryptococcus neoformans, we recently described a more pronounced type 2 immune response in the absence of regulatory T (Treg) cells. To determine whether Treg cell expansion is able to suppress type 2-related fungal allergic inflammation, we increased Treg cell numbers during pulmonaryC. neoformansinfection by administration of an interleukin (IL)-2/anti-IL-2 complex. Expansion of Treg cells resulted in reduced immunoglobulin E production and decreased allergic airway inflammation including reduced production of pulmonary mucus and type 2 cytokines as well as production of immunosuppressive cytokines such as IL-10 and transforming growth factor-β1. From our data we conclude that Treg cells and/or their suppressive mediators represent potential targets for therapeutic intervention during allergic fungal airway disease. PMID:27001975

  16. Staphylococcal Enterotoxin O Exhibits Cell Cycle Modulating Activity

    Science.gov (United States)

    Hodille, Elisabeth; Alekseeva, Ludmila; Berkova, Nadia; Serrier, Asma; Badiou, Cedric; Gilquin, Benoit; Brun, Virginie; Vandenesch, François; Terman, David S.; Lina, Gerard

    2016-01-01

    Maintenance of an intact epithelial barrier constitutes a pivotal defense mechanism against infections. Staphylococcus aureus is a versatile pathogen that produces multiple factors including exotoxins that promote tissue alterations. The aim of the present study is to investigate the cytopathic effect of staphylococcal exotoxins SEA, SEG, SEI, SElM, SElN and SElO on the cell cycle of various human cell lines. Among all tested exotoxins only SEIO inhibited the proliferation of a broad panel of human tumor cell lines in vitro. Evaluation of a LDH release and a DNA fragmentation of host cells exposed to SEIO revealed that the toxin does not induce necrosis or apoptosis. Analysis of the DNA content of tumor cells synchronized by serum starvation after exposure to SEIO showed G0/G1 cell cycle delay. The cell cycle modulating feature of SEIO was confirmed by the flow cytometry analysis of synchronized cells exposed to supernatants of isogenic S. aureus strains wherein only supernatant of the SElO producing strain induced G0/G1 phase delay. The results of yeast-two-hybrid analysis indicated that SEIO’s potential partner is cullin-3, involved in the transition from G1 to S phase. In conclusion, we provide evidence that SEIO inhibits cell proliferation without inducing cell death, by delaying host cell entry into the G0/G1 phase of the cell cycle. We speculate that this unique cell cycle modulating feature allows SEIO producing bacteria to gain advantage by arresting the cell cycle of target cells as part of a broader invasive strategy. PMID:27148168

  17. Modulation of Vascular Cell Function by Bim Expression

    Directory of Open Access Journals (Sweden)

    Margaret E. Morrison

    2013-01-01

    Full Text Available Apoptosis of vascular cells, including pericytes and endothelial cells, contributes to disease pathogenesis in which vascular rarefaction plays a central role. Bim is a proapoptotic protein that modulates not only apoptosis but also cellular functions such as migration and extracellular matrix (ECM protein expression. Endothelial cells and pericytes each make a unique contribution to vascular formation and function although the details require further delineation. Here we set out to determine the cell autonomous impact of Bim expression on retinal endothelial cell and pericyte function using cells prepared from Bim deficient (Bim−/− mice. Bim−/− endothelial cells displayed an increased production of ECM proteins, proliferation, migration, adhesion, and VEGF expression but, a decreased eNOS expression and nitric oxide production. In contrast, pericyte proliferation decreased in the absence of Bim while migration, adhesion, and VEGF expression were increased. In addition, we demonstrated that the coculturing of either wild-type or Bim−/− endothelial cells with Bim−/− pericytes diminished their capillary morphogenesis. Thus, our data further emphasizes the importance of vascular cell autonomous regulatory mechanisms in modulation of vascular function.

  18. Strict vegetarian diet improves the risk factors associated with metabolic diseases by modulating gut microbiota and reducing intestinal inflammation.

    Science.gov (United States)

    Kim, Min-Soo; Hwang, Seong-Soo; Park, Eun-Jin; Bae, Jin-Woo

    2013-10-01

    Low-grade inflammation of the intestine results in metabolic dysfunction, in which dysbiosis of the gut microbiota is intimately involved. Dietary fibre induces prebiotic effects that may restore imbalances in the gut microbiota; however, no clinical trials have been reported in patients with metabolic diseases. Here, six obese subjects with type 2 diabetes and/or hypertension were assigned to a strict vegetarian diet (SVD) for 1 month, and blood biomarkers of glucose and lipid metabolisms, faecal microbiota using 454-pyrosequencing of 16S ribosomal RNA genes, faecal lipocalin-2 and short-chain fatty acids were monitored. An SVD reduced body weight and the concentrations of triglycerides, total cholesterol, low-density lipoprotein cholesterol and haemoglobin A1c, and improved fasting glucose and postprandial glucose levels. An SVD reduced the Firmicutes-to-Bacteroidetes ratio in the gut microbiota, but did not alter enterotypes. An SVD led to a decrease in the pathobionts such as the Enterobacteriaceae and an increase in commensal microbes such as Bacteroides fragilis and Clostridium species belonging to clusters XIVa and IV, resulting in reduced intestinal lipocalin-2 and short-chain fatty acids levels. This study underscores the benefits of dietary fibre for improving the risk factors of metabolic diseases and shows that increased fibre intake reduces gut inflammation by changing the gut microbiota. PMID:24115628

  19. Performance of Photovoltaic Modules of Different Solar Cells

    Directory of Open Access Journals (Sweden)

    Ankita Gaur

    2013-01-01

    Full Text Available In this paper, an attempt of performance evaluation of semitransparent and opaque photovoltaic (PV modules of different generation solar cells, having the maximum efficiencies reported in the literature at standard test conditions (STC, has been carried out particularly for the months of January and June. The outdoor performance is also evaluated for the commercially available semitransparent and opaque PV modules. Annual electrical energy, capitalized cost, annualized uniform cost (unacost, and cost per unit electrical energy for both types of solar modules, namely, semitransparent and opaque have also been computed along with their characteristics curves. Semitransparent PV modules have shown higher efficiencies compared to the opaque ones. Calculations show that for the PV modules made in laboratory, CdTe exhibits the maximum annual electrical energy generation resulting into minimum cost per unit electrical energy, whereas a-Si/nc-Si possesses the maximum annual electrical energy generation giving minimum cost per unit electrical energy when commercially available solar modules are concerned. CIGS has shown the lowest capitalized cost over all other PV technologies.

  20. Proanthocyanidins modulate microRNA expression in human HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Anna Arola-Arnal

    Full Text Available Mi(croRNAs are small non-coding RNAs of 18-25 nucleotides in length that modulate gene expression at the post-transcriptional level. These RNAs have been shown to be involved in a several biological processes, human diseases and metabolic disorders. Proanthocyanidins, which are the most abundant polyphenol class in the human diet, have positive health effects on a variety of metabolic disorders such as inflammation, obesity, diabetes and insulin resistance. The present study aimed to evaluate whether proanthocyanidin-rich natural extracts modulate miRNA expression. Using microarray analysis and Q-PCR, we investigated miRNA expression in HepG2 cells treated with proanthocyanidins. Our results showed that when HepG2 cells were treated with grape seed proanthocyanidin extract (GSPE, cocoa proanthocyanidin extract (CPE or pure epigallocatechin gallate isolated from green tea (EGCG, fifteen, six and five differentially expressed miRNAs, respectively, were identified out of 904 mRNAs. Specifically, miR-30b* was downregulated by the three treatments, and treatment with GSPE or CPE upregulated miR-1224-3p, miR-197 and miR-532-3p. Therefore, these results provide evidence of the capacity of dietary proanthocyanidins to influence microRNA expression, suggesting a new mechanism of action of proanthocyanidins.

  1. Modulation of lens cell adhesion molecules by particle beams

    Science.gov (United States)

    McNamara, M. P.; Bjornstad, K. A.; Chang, P. Y.; Chou, W.; Lockett, S. J.; Blakely, E. A.

    2001-01-01

    Cell adhesion molecules (CAMs) are proteins which anchor cells to each other and to the extracellular matrix (ECM), but whose functions also include signal transduction, differentiation, and apoptosis. We are testing a hypothesis that particle radiations modulate CAM expression and this contributes to radiation-induced lens opacification. We observed dose-dependent changes in the expression of beta 1-integrin and ICAM-1 in exponentially-growing and confluent cells of a differentiating human lens epithelial cell model after exposure to particle beams. Human lens epithelial (HLE) cells, less than 10 passages after their initial culture from fetal tissue, were grown on bovine corneal endothelial cell-derived ECM in medium containing 15% fetal bovine serum and supplemented with 5 ng/ml basic fibroblast growth factor (FGF-2). Multiple cell populations at three different stages of differentiation were prepared for experiment: cells in exponential growth, and cells at 5 and 10 days post-confluence. The differentiation status of cells was characterized morphologically by digital image analysis, and biochemically by Western blotting using lens epithelial and fiber cell-specific markers. Cultures were irradiated with single doses (4, 8 or 12 Gy) of 55 MeV protons and, along with unirradiated control samples, were fixed using -20 degrees C methanol at 6 hours after exposure. Replicate experiments and similar experiments with helium ions are in progress. The intracellular localization of beta 1-integrin and ICAM-1 was detected by immunofluorescence using monoclonal antibodies specific for each CAM. Cells known to express each CAM were also processed as positive controls. Both exponentially-growing and confluent, differentiating cells demonstrated a dramatic proton-dose-dependent modulation (upregulation for exponential cells, downregulation for confluent cells) and a change in the intracellular distribution of the beta 1-integrin, compared to unirradiated controls. In contrast

  2. Differential regulation of intracellular factors mediating cell cycle, DNA repair and inflammation following exposure to silver nanoparticles in human cells

    Directory of Open Access Journals (Sweden)

    AshaRani PV

    2012-02-01

    Full Text Available Abstract Background Investigating the cellular and molecular signatures in eukaryotic cells following exposure to nanoparticles will further our understanding on the mechanisms mediating nanoparticle induced effects. This study illustrates the molecular effects of silver nanoparticles (Ag-np in normal human lung cells, IMR-90 and human brain cancer cells, U251 with emphasis on gene expression, induction of inflammatory mediators and the interaction of Ag-np with cytosolic proteins. Results We report that silver nanoparticles are capable of adsorbing cytosolic proteins on their surface that may influence the function of intracellular factors. Gene and protein expression profiles of Ag-np exposed cells revealed up regulation of many DNA damage response genes such as Gadd 45 in both the cell types and ATR in cancer cells. Moreover, down regulation of genes necessary for cell cycle progression (cyclin B and cyclin E and DNA damage response/repair (XRCC1 and 3, FEN1, RAD51C, RPA1 was observed in both the cell lines. Double strand DNA damage was observed in a dose dependant manner as evidenced in γH2AX foci assay. There was a down regulation of p53 and PCNA in treated cells. Cancer cells in particular showed a concentration dependant increase in phosphorylated p53 accompanied by the cleavage of caspase 3 and PARP. Our results demonstrate the involvement of NFκB and MAP kinase pathway in response to Ag-np exposure. Up regulation of pro-inflammatory cytokines such as interleukins (IL-8, IL-6, macrophage colony stimulating factor, macrophage inflammatory protein in fibroblasts following Ag-np exposure were also observed. Conclusion In summary, Ag-np can modulate gene expression and protein functions in IMR-90 cells and U251 cells, leading to defective DNA repair, proliferation arrest and inflammatory response. The observed changes could also be due to its capability to adsorb cytosolic proteins on its surface.

  3. Purinergic Receptors in Ocular Inflammation

    Directory of Open Access Journals (Sweden)

    Ana Guzman-Aranguez

    2014-01-01

    Full Text Available Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly “tuned,” can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P1,P4-diadenosine tetraphosphate (Ap4A, and P1,P5-diadenosine pentaphosphate (Ap5A are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N6-(3-iodobenzyl-5′-N-methylcarboxamidoadenosine (CF101 have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation.

  4. Infrared modulation spectroscopy of interfaces in amorphous silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Kai; Schiff, E.A. [Department of Physics, Syracuse University, 13244-1130 Syracuse, NY (United States); Ganguly, G. [BP Solar, 23168 Toano, VA (United States)

    2002-04-01

    We report infrared depletion modulation spectra for near-interface states in a-Si pin solar cells. The effect of additional visible illumination (optical bias) was explored as a means to separate the spectra for n/i and p/i interface states. We found a sharp, optical bias-induced spectral line near 0.8 eV. We attribute this line due to internal optical transitions of dopant-defect complexes in the a-SiC:H:B p-layer of the cells. We discuss the spatial location of the depletion modulation regions, and suggest that this location shifts across the n/i and p/i interfaces for cells with differing deposition and illumination conditions.

  5. Synthesized OVA323-339MAP octamers mitigate OVA-induced airway inflammation by regulating Foxp3 T regulatory cells

    Directory of Open Access Journals (Sweden)

    Su Wen

    2012-07-01

    Full Text Available Abstract Background Antigen-specific immunotherapy (SIT has been widely practiced in treating allergic diseases such as asthma. However, this therapy may induce a series of allergic adverse events during treatment. Peptide immunotherapy (PIT was explored to overcome these disadvantages. We confirmed that multiple antigen peptides (MAPs do not cause autoimmune responses, which led to the presumption that MAPs intervention could alleviate allergic airway inflammation without inducing adverse effects. Results In this study, synthesized OVA323-339MAP octamers were subcutaneously injected into ovalbumin (OVA-sensitized and -challenged Balb/c mice to observe its effect on allergic airway inflammation, Th2 immune response, and immune regulating function. It was confirmed that OVA sensitization and challenge led to significant peritracheal inflammatory, cell infiltration, and intensive Th2 response. Treatment of OVA323-339MAP octomers in the airway inflammation mice model increased CD4+CD25+Foxp3+ T regulatory (Treg cells and their regulatory function in peripheral blood, mediastinal draining lymph nodes, and the spleen. Furthermore, OVA323-339MAP increased IL-10 levels in bronchial alveolar lavage fluid (BALF; up-regulated the expression of IL-10, membrane-bound TGF-β1, as well as Foxp3 in lung tissues; and up-regulated programmed death-1 (PD-1 and cytotoxic T lymphocyte associated antigen 4 (CTLA-4 on the surface of Treg cells. These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF. However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model. Conclusions Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.

  6. Molecular mechanisms involved in TFF3 peptide-mediated modulation of the E-cadherin/catenin cell adhesion complex.

    Science.gov (United States)

    Meyer zum Büschenfelde, Dirk; Hoschützky, Heinz; Tauber, Rudolf; Huber, Otmar

    2004-05-01

    TFF3 is a member of the TFF-domain peptide family which is constitutively expressed in mucous epithelial tissues where it acts as a motogenic factor and plays an important role during epithelial restitution after wounding and during inflammation. In contrast to these beneficial functions, TFFs were also reported to be involved in cell scattering and tumor invasion. These changes in epithelial cell morphology and motility are associated with a modulation of cell contacts. In this respect, we here investigated the E-cadherin/catenin cell adhesion complex in FLAG-hTFF3-transfected HT29/B6 and MDCK cells. In hTFF3-transfected cells the amount of E-cadherin is reduced with a concomitant reduction of alpha- and beta-catenin levels. On one hand, E-cadherin expression is lowered at the transcriptional level as shown by multiplex RT-PCR analysis. This decrease does not depend on differences in the promoter methylation status as shown by methylation-specific PCR. On the other hand, pulse-chase experiments showed a reduction in the E-cadherin half-life in hTFF3-transfected cells reflecting increased E-cadherin degradation. In summary, hTFF3 induces transcriptional and posttranslational processes resulting in a modulation of E-cadherin-mediated cell-cell contacts that may play an important role in the paradoxical benefical and pathogenic function of TFF peptides.

  7. Antigen-specific cytotoxic T lymphocytes target airway CD103+ and CD11b+ dendritic cells to suppress allergic inflammation.

    Science.gov (United States)

    Daniels, N J; Hyde, E; Ghosh, S; Seo, K; Price, K M; Hoshino, K; Kaisho, T; Okada, T; Ronchese, F

    2016-01-01

    Allergic airway inflammation is driven by the recognition of inhaled allergen by T helper type 2 (Th2) cells in the airway and lung. Allergen-specific cytotoxic T lymphocytes (CTLs) can strongly reduce airway inflammation, however, the mechanism of their inhibitory activity is not fully defined. We used mouse models to show that allergen-specific CTLs reduced early cytokine production by Th2 cells in lung, and their subsequent accumulation and production of interleukin (IL)-4 and IL-13. In addition, treatment with specific CTLs also increased the proportion of caspase(+) dendritic cells (DCs) in mediastinal lymph node (MLN), and decreased the numbers of CD103(+) and CD11b(+) DCs in the lung. This decrease required expression of the cytotoxic mediator perforin in CTLs and of the appropriate MHC-antigen ligand on DCs, suggesting that direct CTL-DC contact was necessary. Lastly, lung imaging experiments revealed that in airway-challenged mice XCR1-GFP(+) DCs, corresponding to the CD103(+) DC subset, and XCR1-GFP(-) CD11c(+) cells, which include CD11b(+) DCs and alveolar macrophages, both clustered in the areas surrounding the small airways and were closely associated with allergen-specific CTLs. Thus, allergen-specific CTLs reduce allergic airway inflammation by depleting CD103(+) and CD11b(+) DC populations in the lung, and may constitute a mechanism through which allergic immune responses are regulated.

  8. Allergen-Experienced Group 2 Innate Lymphoid Cells Acquire Memory-like Properties and Enhance Allergic Lung Inflammation.

    Science.gov (United States)

    Martinez-Gonzalez, Itziar; Mathä, Laura; Steer, Catherine A; Ghaedi, Maryam; Poon, Grace F T; Takei, Fumio

    2016-07-19

    Group 2 innate lymphoid cells (ILC2s) in the lung are stimulated by inhaled allergens. ILC2s do not directly recognize allergens but they are stimulated by cytokines including interleukin (IL)-33 released by damaged epithelium. In response to allergens, lung ILC2s produce T helper 2 cell type cytokines inducing T cell-independent allergic lung inflammation. Here we examined the fate of lung ILC2s upon allergen challenges. ILC2s proliferated and secreted cytokines upon initial stimulation with allergen or IL-33, and this phase was followed by a contraction phase as cytokine production ceased. Some ILC2s persisted long after the resolution of the inflammation as allergen-experienced ILC2s and responded to unrelated allergens more potently than naive ILC2s, mediating severe allergic inflammation. The allergen-experienced ILC2s exhibited a gene expression profile similar to that of memory T cells. The memory-like properties of allergen-experienced ILC2s may explain why asthma patients are often sensitized to multiple allergens. PMID:27421705

  9. Iron- and inflammation-induced hepcidin gene expression in mice is not mediated by Kupffer cells in vivo.

    Science.gov (United States)

    Lou, Dan-Qing; Lesbordes, Jeanne-Claire; Nicolas, Gaël; Viatte, Lydie; Bennoun, Myriam; Van Rooijen, Nico; Kahn, Axel; Renia, Laurent; Vaulont, Sophie

    2005-05-01

    Hepcidin, a recently discovered iron regulatory peptide, is believed to inhibit the release of iron from absorptive enterocytes and macrophages. Liver hepcidin synthesis is induced in vivo by iron stores and inflammation. The molecular basis of the regulation of hepcidin gene expression by these effectors in hepatocytes is currently unknown, although there is strong evidence that indirect mechanisms are involved. The aims of this study were to gain insight into these mechanisms and to determine to what extent other liver cell types are responsible for transducing the signal by which hepcidin expression is regulated in mouse hepatocytes. For this, we depleted Kupffer cells by injection of liposome-encapsulated clodronate and then studied iron- and inflammation-induced hepcidin gene expression. In addition, we directly evaluated the role of the inflammatory cytokine interleukin 6 (IL-6) by using IL-6-deficient mice. Our results show that iron is able to induce hepcidin gene expression independently of Kupffer cells in the liver and circulating IL-6. In contrast, we show that hepcidin gene induction by inflammation is also independent of Kupffer cells, but involves, at least partly, IL-6. In conclusion, these results show that two independent regulatory pathways control hepcidin gene expression and suggest that hepatocytes play a key role in the regulation of hepcidin gene expression by sensing iron and inflammatory signals. PMID:15793843

  10. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Andrej Udelnow

    Full Text Available BACKGROUND: Omeprazole has recently been described as a modulator of tumour chemoresistance, although its underlying molecular mechanisms remain controversial. Since pancreatic tumours are highly chemoresistant, a logical step would be to investigate the pharmacodynamic, morphological and biochemical effects of omeprazole on pancreatic cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Dose-effect curves of omeprazole, pantoprazole, gemcitabine, 5-fluorouracil and the combinations of omeprazole and 5-fluorouracil or gemcitabine were generated for the pancreatic cancer cell lines MiaPaCa-2, ASPC-1, Colo357, PancTu-1, Panc1 and Panc89. They revealed that omeprazole inhibited proliferation at probably non-toxic concentrations and reversed the hormesis phenomena of 5-fluorouracil. Electron microscopy showed that omeprazole led to accumulation of phagophores and early autophagosomes in ASPC-1 and MiaPaCa-2 cells. Signal changes indicating inhibited proliferation and programmed cell death were found by proton NMR spectroscopy of both cell lines when treated with omeprazole which was identified intracellularly. Omeprazole modulates the lysosomal transport pathway as shown by Western blot analysis of the expression of LAMP-1, Cathepsin-D and β-COP in lysosome- and Golgi complex containing cell fractions. Acridine orange staining revealed that the pump function of the vATPase was not specifically inhibited by omeprazole. Gene expression of the autophagy-related LC3 gene as well as of Bad, Mdr-1, Atg12 and the vATPase was analysed after treatment of cells with 5-fluorouracil and omeprazole and confirmed the above mentioned results. CONCLUSIONS: We hypothesise that omeprazole interacts with the regulatory functions of the vATPase without inhibiting its pump function. A modulation of the lysosomal transport pathway and autophagy is caused in pancreatic cancer cells leading to programmed cell death. This may circumvent common resistance mechanisms of

  11. Cell wall remodelling enzymes modulate fungal cell wall elasticity and osmotic stress resistance

    OpenAIRE

    Ene, Iuliana; Walker, Louise; Schiavone, Marion; Lee, Keunsook K.; Dague, Etienne; Gow, Neil A.R.; Munro, Carol A

    2015-01-01

    The fungal cell wall confers cell morphology and protection against environmental insults. For fungal pathogens, the cell wall is a key immunological modulator and an ideal therapeutic target. Yeast cell walls possess an inner matrix of interlinked β-glucan and chitin that is thought to provide tensile strength and rigidity. Yeast cells remodel their walls over time in response to environmental change, a process controlled by evolutionarily conserved stress (Hog1) and cell integrity (Mkc1, Ce...

  12. Stem Cell-Derived Extracellular Vesicles and Immune-Modulation.

    Science.gov (United States)

    Burrello, Jacopo; Monticone, Silvia; Gai, Chiara; Gomez, Yonathan; Kholia, Sharad; Camussi, Giovanni

    2016-01-01

    Extra-cellular vesicles (EVs) are bilayer membrane structures enriched with proteins, nucleic acids, and other active molecules and have been implicated in many physiological and pathological processes over the past decade. Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) immune responses, as Ag carriers or presenters, or as vehicles for delivering active signaling molecules. On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species), and cytokines. In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation, and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content, and functional state of both parental and target cells. However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review, we will discuss how stem cell-derived EVs may contribute toward the modulation of the immune response. Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system. PMID:27597941

  13. The macrophage low-grade inflammation marker sCD163 is modulated by exogenous sex steroids

    DEFF Research Database (Denmark)

    Thomsen, Henrik Holm; Møller, Holger Jon; Trolle, Christian;

    2013-01-01

    Soluble CD163 (sCD163) is a novel marker linked to states of low grade inflammation such as diabetes, obesity, liver disease and atherosclerosis, all prevalent in subjects with Turner and Klinefelter Syndromes. We aimed to assess the levels of sCD163 and the regulation of sCD163 in regards...... to treatment with sex hormone therapy in males with and without Klinefelter Syndrome and females with and without Turner Syndrome. Males with Klinefelter Syndrome (n=70) and age-matched controls (n=71) participating in a cross-sectional study and 12 healthy males from an experimental hypogonadism study....... Females with Turner Syndrome (n=8) and healthy age- matched controls (n=8) participating in a randomized cross-over trial. The intervention comprised of treatment with sex steroids. Males with Klinefelter Syndrome had higher levels of sCD163 compared with controls (1.75 (0.47-6.90) and 1.36 (0...

  14. Protective Effects of Surfactant Protein D (SP-D) Treatment in 1,3-β-glucan-modulated Allergic Inflammation

    DEFF Research Database (Denmark)

    Fakih, Dalia; Pilecki, Bartosz; Schlosser, Anders;

    2015-01-01

    -glucans are a diverse group of polysaccharides previously suggested to serve as fungal ligands for SP-D. We set out to investigate if SP-D could interact with 1,3-β-glucan and attenuate allergic pulmonary inflammation in the presence of 1,3-β-glucan. Allergic airway disease was induced in Sftpd(-/-) and Sftpd(+/+) mice...... by OVA sensitization and subsequent challenge with OVA, 1,3-β-glucan or OVA/1,3-β-glucan together. Mice in the combined treatment group were further treated with a high dose of recombinant fragment of human SP-D (rfhSP-D). We demonstrated direct interaction between SP-D and 1,3-β-glucan. OVA...

  15. Study on cytokine modulation in mast cell-induced allergic reactions by using gamma-irradiated natural herbal extracts

    Energy Technology Data Exchange (ETDEWEB)

    Gwon, Hui Jeong; Lim, Youn Mook; Kim, Yong Soo; Nho, Young Chang [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Kim Hae Kyoung [Chonbuk National University, Jeonju (Korea, Republic of)

    2009-12-15

    We previously described that some natural herbal extracts such as Houttuynia cordata (H), Centella asiatica (C), Plantago asiatica (P), Morus alba L. (M), and Ulmus davidiana (U), differentially suppress an atopic dermatitis like skin lesions. The objective of this study was to evaluate the pro-inflammatory cytokine modulation of the water extract of the H, C, P, M, U, and those mixtures (M) and their mechanism in a phorbol myristate acetate (PMA) plus calcium inopore A23187 treated human mast cell line (HMC-1). The H, C, P, M, U, and M inhibited the inflammatory cytokines such as TNF-{alpha}, IL-6 and IL-8 stimulated by PMA plus A23187 from HMC-1 cells. In addition, the M did not significantly affect the cell viability and had no toxicity on the HMC-1 cells. Based on these results, M can be used for the treatment of an allergic inflammation response.

  16. Cardiopulmonary bypass during cardiac surgery modulates systemic inflammation by affecting different steps of the leukocyte recruitment cascade.

    Directory of Open Access Journals (Sweden)

    Jan Rossaint

    Full Text Available BACKGROUND: It is known that the use of a cardiopulmonary bypass (CPB during cardiac surgery leads to leukocyte activation and may, among other causes, induce organ dysfunction due to increased leukocyte recruitment into different organs. Leukocyte extravasation occurs in a cascade-like fashion, including capturing, rolling, adhesion, and transmigration. However, the molecular mechanisms of increased leukocyte recruitment caused by CPB are not known. This clinical study was undertaken in order to investigate which steps of the leukocyte recruitment cascade are affected by the systemic inflammation during CPB. METHODS: We investigated the effects of CPB on the different steps of the leukocyte recruitment cascade in whole blood from healthy volunteers (n = 9 and patients undergoing cardiac surgery with the use of cardiopulmonary bypass (n = 7 or in off-pump coronary artery bypass-technique (OPCAB, n = 9 by using flow chamber experiments, transmigration assays, and biochemical analysis. RESULTS: CPB abrogated selectin-induced slow leukocyte rolling on E-selectin/ICAM-1 and P-selectin/ICAM-1. In contrast, chemokine-induced arrest and transmigration was significantly increased by CPB. Mechanistically, the abolishment of slow leukocyte rolling was due to disturbances in intracellular signaling with reduced phosphorylation of phospholipase C (PLC γ2, Akt, and p38 MAP kinase. Furthermore, CPB induced an elevated transmigration which was caused by upregulation of Mac-1 on neutrophils. CONCLUSION: These data suggest that CPB abrogates selectin-mediated slow leukocyte rolling by disturbing intracellular signaling, but that the clinically observed increased leukocyte recruitment caused by CPB is due to increased chemokine-induced arrest and transmigration. A better understanding of the underlying molecular mechanisms causing systemic inflammation after CPB may aid in the development of new therapeutic approaches.

  17. Xanthohumol-supplemented beer modulates angiogenesis and inflammation in a skin wound healing model. Involvement of local adipocytes.

    Science.gov (United States)

    Negrão, Rita; Costa, Raquel; Duarte, Delfim; Gomes, Tiago Taveira; Coelho, Pedro; Guimarães, João T; Guardão, Luísa; Azevedo, Isabel; Soares, Raquel

    2012-01-01

    Angiogenesis and inflammation are two intermingled processes that play a role in wound healing. Nevertheless, whenever exacerbated, these processes result in nonhealing wounds. Xanthohumol (XN), a beer-derived polyphenol, inhibits these processes in many physiopathological situations. This study aimed at examining whether XN ingestion affects wound healing. Wistar rats drinking water, 5% ethanol, stout beer (SB) or stout beer supplemented with 10 mg/L XN (Suppl SB) for 4 weeks, were subjected to a 1.5 cm full skin-thickness longitudinal incision, and further maintained under the same beverage conditions for another week. No differences in beverage consumption or body weight were found throughout the study but food intake decreased in every group relative to controls. Consumption of Suppl SB resulted in decreased serum VEGF levels (18.42%), N-acetylglucosaminidase activity (27.77%), IL1β concentration (9.07%), and NO released (77.06%), accompanied by a reduced redox state as observed by increased GSH/GSSG ratio (to 198.80%). Also, the number of blood vessels within the wound granulation tissue seems to reduce in animals drinking Suppl SB (23.08%). Interestingly, SB and primarily Suppl SB showed a tendency to increase adipocyte number (to 194.26% and 156.68%, respectively) and reduce adipocyte size (4.60% and 24.64%, respectively) within the granuloma. Liver function and metabolism did not change among the animal groups as analyzed by plasma biochemical parameters, indicating no beverage toxicity. This study shows that XN intake in its natural beer context reduced inflammation, oxidative stress, and angiogenesis, ameliorating the wound healing process, suggesting that this polyphenol may exert beneficial effect as a nutritional supplement. PMID:21898537

  18. Polycrystalline thin-film solar cells and modules

    Energy Technology Data Exchange (ETDEWEB)

    Ullal, H.S.; Stone, J.L.; Zweibel, K.; Surek, T.; Mitchell, R.L.

    1991-12-01

    This paper describes the recent technological advances in polycrystalline thin-film solar cells and modules. Three thin film materials, namely, cadmium telluride (CdTe), copper indium diselenide (CuInSe{sub 2}, CIS) and silicon films (Si-films) have made substantial technical progress, both in device and module performance. Early stability results for modules tested outdoors by various groups worldwide are also encouraging. The major global players actively involved in the development of the these technologies are discussed. Technical issues related to these materials are elucidated. Three 20-kW polycrystalline thin-film demonstration photovoltaic (PV) systems are expected to be installed in Davis, CA in 1992 as part of the Photovoltaics for Utility-Scale Applications (PVUSA) project. This is a joint project between the US Department of Energy (DOE), Pacific Gas and Electric (PG&E), Electric Power Research Institute (EPRI), California Energy Commission (CEC), and a utility consortium.

  19. Polycrystalline thin-film solar cells and modules

    Energy Technology Data Exchange (ETDEWEB)

    Ullal, H.S.; Stone, J.L.; Zweibel, K.; Surek, T.; Mitchell, R.L.

    1991-12-01

    This paper describes the recent technological advances in polycrystalline thin-film solar cells and modules. Three thin film materials, namely, cadmium telluride (CdTe), copper indium diselenide (CuInSe{sub 2}, CIS) and silicon films (Si-films) have made substantial technical progress, both in device and module performance. Early stability results for modules tested outdoors by various groups worldwide are also encouraging. The major global players actively involved in the development of the these technologies are discussed. Technical issues related to these materials are elucidated. Three 20-kW polycrystalline thin-film demonstration photovoltaic (PV) systems are expected to be installed in Davis, CA in 1992 as part of the Photovoltaics for Utility-Scale Applications (PVUSA) project. This is a joint project between the US Department of Energy (DOE), Pacific Gas and Electric (PG E), Electric Power Research Institute (EPRI), California Energy Commission (CEC), and a utility consortium.

  20. New test and characterization methods for PV modules and cells

    Energy Technology Data Exchange (ETDEWEB)

    Van Aken, B.; Sommeling, P. [ECN Solar Energy, Petten (Netherlands); Scholten, H. [Solland, Heerlen (Netherlands); Muller, J. [Moser-Baer, Eindhoven (Netherlands); Grossiord, N. [Holst Centre, Eindhoven (Netherlands); Smits, C.; Blanco Mantecon, M. [Holland Innovative, Eindhoven (Netherlands); Verheijen, M.; Van Berkum, J. [Philips Innovation Services, Eindhoven (Netherlands)

    2012-08-15

    The results of the project geZONd (shared facility for solar module analysis and reliability testing) are described. The project was set up by Philips, ECN, Holst, Solland, OM and T and Holland Innovative. The partners have shared most of their testing and analysis equipment for PV modules and cells, and together developed new or improved methods (including the necessary application know-how). This enables faster and more efficient innovation projects for each partner, and via commercial exploitation for other interested parties. The project has concentrated on five failure modes: corrosion, delamination, moisture ingress, UV irradiation, and mechanical bending. Test samples represented all main PV technologies: wafer based PV and rigid and flexible thin-film PV. Breakthroughs are in very early detection of corrosion, in quantitative characterization of adhesion, in-situ detection of humidity and oxygen inside modules, and ultra-fast screening of materials on UV stability.

  1. Antagonizing Arachidonic Acid-Derived Eicosanoids Reduces Inflammatory Th17 and Th1 Cell-Mediated Inflammation and Colitis Severity

    Directory of Open Access Journals (Sweden)

    Jennifer M. Monk

    2014-01-01

    Full Text Available During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA- derived eicosanoids, such as prostaglandin E2 (PGE2, promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS- induced colitis. Fat-1 mice contain the ω3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Δ5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORγτ, and IL-23, decreased percentages of Th17 cells and, improved colon injury scores (P≤0.05. Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.

  2. miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation.

    OpenAIRE

    Hu, Ruozhen; Kagele, Dominique A; Huffaker, Thomas B; Runtsch, Marah C; Alexander, Margaret; Liu, Jin; Bake, Erin; Su, Wei; Williams, Matthew A.; Rao, Dinesh S.; Möller, Thomas; Garden, Gwenn A; Round, June L.; O’Connell, Ryan M.

    2014-01-01

    Chronic inflammation is a contributing factor to most life shortening human diseases. However, the molecular and cellular mechanisms that sustain chronic inflammatory responses remain poorly understood making it difficult to treat this deleterious condition. Using a mouse model of age-dependent inflammation that results from a deficiency in miR-146a, we demonstrate that miR-155 contributed to the progressive inflammatory disease that emerged as Mir146a−/− mice grew older. Upon analyzing lymph...

  3. Comparison of photovoltaic cell temperatures in modules operating with exposed and enclosed back surfaces

    Science.gov (United States)

    Namkoong, D.; Simon, F. F.

    1981-01-01

    Four different photovoltaic module designs were tested to determine the cell temperature of each design. The cell temperatures were compared to those obtained on identical design, using the same nominal operating cell temperature (NOCT) concept. The results showed that the NOCT procedure does not apply to the enclosed configurations due to continuous transient conditions. The enclosed modules had higher cell temperatures than the open modules, and insulated modules higher than the uninsulated. The severest performance loss - when translated from cell temperatures - 17.5 % for one enclosed, insulated module as a compared to that module mounted openly.

  4. Systemic inflammation in 222.841 healthy employed smokers and nonsmokers: white blood cell count and relationship to spirometry

    OpenAIRE

    Fernández José Antonio; Prats Josép; Artero José Vicente; Mora Alberto; Fariñas Anna; Espinal Anna; Méndez José Antonio

    2012-01-01

    Abstract Background Smoking has been linked to low-grade systemic inflammation, a known risk factor for disease. This state is reflected in elevated white blood cell (WBC) count. Objective We analyzed the relationship between WBC count and smoking in healthy men and women across several age ranges who underwent preventive medical check-ups in the workplace. We also analysed the relationship between smoking and lung function. Methods Cross-sectional descriptive study in 163 459 men and 59 382 ...

  5. CdTe Thin Film Solar Cells and Modules Tutorial; NREL (National Renewable Energy Laboratory)

    Energy Technology Data Exchange (ETDEWEB)

    Albin, David S.

    2015-06-13

    This is a tutorial presented at the 42nd IEEE Photovoltaics Specialists Conference to cover the introduction, background, and updates on CdTe cell and module technology, including CdTe cell and module structure and fabrication.

  6. Attenuation of oxidative stress and inflammation by gravinol in high glucose-exposed renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Gravinol, a proanthocyanidin from grape seeds, has polyphenolic properties with powerful anti-oxidative effects. Although, increasing evidence strongly suggests that polyphenolic antioxidants suppress diabetic nephropathy that is causally associated with oxidative stress and inflammation, gravinol's protective action against diabetic nephropathy has not been fully explored to date. In the current study, we investigated the protective action of gravinol against oxidative stress and inflammation using the experimental diabetic nephropathy cell model, high glucose-exposed renal tubular epithelial cells. To elucidate the underlying actions of gravinol, several oxidative and inflammatory markers were estimated. Included are measurements of lipid peroxidation, total reactive species (RS), superoxide (·O2), nitric oxide (NO·), and peroxynitrite (ONOO-), as well as nuclear factor-kappa B (NF-κB) nuclear translocation. Results indicate that gravinol had a potent inhibitory action against lipid peroxidation, total RS, ·O2, NO·, ONOO-, the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio and more importantly, against NF-κB nuclear translocation. We propose that gravinol's strong protective effect against high glucose-induced renal tubular epithelial cell damage attenuates diabetic nephropathy by suppressing oxidative stress and inflammation.

  7. B cells as a target of immune modulation

    Directory of Open Access Journals (Sweden)

    Hawker Kathleen

    2009-01-01

    Full Text Available B cells have recently been identified as an integral component of the immune system; they play a part in autoimmunity through antigen presentation, antibody secretion, and complement activation. Animal models of multiple sclerosis (MS suggest that myelin destruction is partly mediated through B cell activation (and plasmablasts. MS patients with evidence of B cell involvement, as compared to those without, tend to have a worse prognosis. Finally, the significant decrease in new gadolinium-enhancing lesions, new T2 lesions, and relapses in MS patients treated with rituximab (a monoclonal antibody against CD20 on B cells leads us to the conclusion that B cells play an important role in MS and that immune modulation of these cells may ameliorate the disease. This article will explore the role of B cells in MS and the rationale for the development of B cell-targeted therapeutics. MS is an immune-mediated disease that affects over 2 million people worldwide and is the number one cause of disability in young patients. Most therapeutic targets have focused on T cells; however, recently, the focus has shifted to the role of B cells in the pathogenesis of MS and the potential of B cells as a therapeutic target.

  8. Indole-3-carbinol and 3’, 3’-diindolylmethane modulate androgen effect up-regulation on C-C chemokine ligand 2 and monocyte attraction to prostate cancer cells

    Science.gov (United States)

    Inflammation has a role in prostate tumorigenesis. Recruitment of inflammatory monocytes to the tumor site is mediated by C-C chemokine ligand 2 (CCL2) through binding to its receptor CCR2. We hypothesized that androgen could modulate CCL2 expression in hormone-responsive prostate cancer cells, and ...

  9. Mast cells modulate transport of CD23/IgE/antigen complex across human intestinal epithelial barrier

    Directory of Open Access Journals (Sweden)

    Ping-Chang Yang

    2009-06-01

    Full Text Available Background: Food allergy and chronic intestinal inflammation are common in western countries. The complex of antigen/IgE is taken up into the body from the gut lumen with the aid of epithelial cell-derived CD23 (low affinity IgE receptor II that plays an important role in the pathogenesis of intestinal allergy. This study aimed to elucidate the role of mast cell on modulation of antigen/IgE complex transport across intestinal epithelial barrier. Methods: Human intestinal epithelial cell line HT29 cell monolayer was used as a study platform. Transepithelial electric resistance (TER and permeability to ovalbumin (OVA were used as the markers of intestinal epithelial barrier function that were recorded in response to the stimulation of mast cell-derived chemical mediators. Results: Conditioned media from naïve mast cell line HMC-1 cells or monocyte cell line THP-1 cells significantly upregulated the expression of CD23 and increased the antigen transport across the epithelium. Treatment with stem cell factor (SCF, nerve growth factor (NGF, retinoic acid (RA or dimethyl sulphoxide (DMSO enhanced CD23 expression in HT29 cells. Conditioned media from SCF, NGF or RA-treated HMC-1 cells, and SCF, NGF, DMSO or RA-treated THP-1 cells enhanced immune complex transport via enhancing the expression of the CD23 in HT29 cells and the release of inflammatory mediator TNF-α. Nuclear factor kappa B inhibitor, tryptase and TNF-α inhibited the increase in CD23 in HT29 cells and prevents the enhancement of epithelial barrier permeability. Conclusions: Mast cells play an important role in modulating the intestinal CD23 expression and the transport of antigen/IgE/CD23 complex across epithelial barrier.

  10. Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus

    Directory of Open Access Journals (Sweden)

    Jasmin Luc

    2010-12-01

    Full Text Available Abstract Background Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS. Indeed, glial cell activation has been reported in both the dorsal root ganglia and the spinal cord following injury or inflammation of the sciatic nerve, but no data are currently available in animal models of trigeminal sensitization. Therefore, in the present study, we evaluated glial cell activation in the trigeminal-spinal system following injection of the Complete Freund's Adjuvant (CFA into the temporomandibular joint, which generates inflammatory pain and trigeminal hypersensitivity. Results CFA-injected animals showed ipsilateral mechanical allodynia and temporomandibular joint edema, accompanied in the trigeminal ganglion by a strong increase in the number of GFAP-positive satellite glial cells encircling neurons and by the activation of resident macrophages. Seventy-two hours after CFA injection, activated microglial cells were observed in the ipsilateral trigeminal subnucleus caudalis and in the cervical dorsal horn, with a significant up-regulation of Iba1 immunoreactivity, but no signs of reactive astrogliosis were detected in the same areas. Since the purinergic system has been implicated in the activation of microglial cells during neuropathic pain, we have also evaluated the expression of the microglial-specific P2Y12 receptor subtype. No upregulation of this receptor was detected following induction of TMJ inflammation, suggesting that any possible role of P2Y12 in this paradigm of inflammatory pain does not involve changes in receptor expression. Conclusions Our data indicate that specific glial cell populations become activated in both the trigeminal ganglia and the CNS following induction of temporomandibular joint inflammation, and suggest that they might represent innovative targets for controlling pain during trigeminal nerve sensitization.

  11. Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals

    Directory of Open Access Journals (Sweden)

    Catarina Marques

    2014-01-01

    Full Text Available This study aimed to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV inhibitor, in preventing the deleterious effects of diabetes on the kidney in an animal model of type 2 diabetes mellitus; the Zucker diabetic fatty (ZDF rat: 20-week-old rats were treated with sitagliptin (10 mg/kg bw/day during 6 weeks. Glycaemia and blood HbA1c levels were monitored, as well as kidney function and lesions. Kidney mRNA and/or protein content/distribution of DPP-IV, GLP-1, GLP-1R, TNF-α, IL-1β, BAX, Bcl-2, and Bid were evaluated by RT-PCR and/or western blotting/immunohistochemistry. Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia and HbA1c (by about 22.5% and 1.2%, resp. and ameliorated tubulointerstitial and glomerular lesions. Sitagliptin prevented the diabetes-induced increase in DPP-IV levels and the decrease in GLP-1 levels in kidney. Sitagliptin increased colocalization of GLP-1 and GLP-1R in the diabetic kidney. Sitagliptin also decreased IL-1β and TNF-α levels, as well as, prevented the increase of BAX/Bcl-2 ratio, Bid protein levels, and TUNEL-positive cells which indicates protective effects against inflammation and proapoptotic state in the kidney of diabetic rats, respectively. In conclusion, sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and antiapoptotic properties.

  12. Radio-frequency-modulated Rydberg states in a vapor cell

    CERN Document Server

    Miller, Stephanie A; Raithel, Georg

    2016-01-01

    We measure strong radio-frequency (RF) electric fields using rubidium Rydberg atoms prepared in a room-temperature vapor cell as field sensors. Electromagnetically induced transparency is employed as an optical readout. We RF-modulate the 60$S_{1/2}$ and 58$D_{5/2}$ Rydberg states with 50~MHz and 100~MHz fields, respectively. For weak to moderate RF fields, the Rydberg levels become Stark-shifted, and sidebands appear at even multiples of the driving frequency. In high fields, the adjacent hydrogenic manifold begins to intersect the shifted levels, providing rich spectroscopic structure suitable for precision field measurements. A quantitative description of strong-field level modulation and mixing of $S$ and $D$ states with hydrogenic states is provided by Floquet theory. Additionally, we estimate the shielding of DC electric fields in the interior of the glass vapor cell.

  13. The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation.

    Science.gov (United States)

    Kabat, Agnieszka M; Harrison, Oliver J; Riffelmacher, Thomas; Moghaddam, Amin E; Pearson, Claire F; Laing, Adam; Abeler-Dörner, Lucie; Forman, Simon P; Grencis, Richard K; Sattentau, Quentin; Simon, Anna Katharina; Pott, Johanna; Maloy, Kevin J

    2016-01-01

    A polymorphism in the autophagy gene Atg16l1 is associated with susceptibility to inflammatory bowel disease (IBD); however, it remains unclear how autophagy contributes to intestinal immune homeostasis. Here, we demonstrate that autophagy is essential for maintenance of balanced CD4(+) T cell responses in the intestine. Selective deletion of Atg16l1 in T cells in mice resulted in spontaneous intestinal inflammation that was characterized by aberrant type 2 responses to dietary and microbiota antigens, and by a loss of Foxp3(+) Treg cells. Specific ablation of Atg16l1 in Foxp3(+) Treg cells in mice demonstrated that autophagy directly promotes their survival and metabolic adaptation in the intestine. Moreover, we also identify an unexpected role for autophagy in directly limiting mucosal TH2 cell expansion. These findings provide new insights into the reciprocal control of distinct intestinal TH cell responses by autophagy, with important implications for understanding and treatment of chronic inflammatory disorders. PMID:26910010

  14. Hsp90 modulates CAG repeat instability in human cells

    OpenAIRE

    Mittelman, David; Sykoudis, Kristen; Hersh, Megan; Lin, Yunfu; Wilson, John H.

    2010-01-01

    The Hsp90 molecular chaperone has been implicated as a contributor to evolution in several organisms by revealing cryptic variation that can yield dramatic phenotypes when the chaperone is diverted from its normal functions by environmental stress. In addition, as a cancer drug target, Hsp90 inhibition has been documented to sensitize cells to DNA-damaging agents, suggesting a function for Hsp90 in DNA repair. Here we explore the potential role of Hsp90 in modulating the stability of nucleoti...

  15. Protective effect of cannabidiol on hydrogen peroxide‑induced apoptosis, inflammation and oxidative stress in nucleus pulposus cells.

    Science.gov (United States)

    Chen, Jie; Hou, Chen; Chen, Xin; Wang, Dong; Yang, Pinglin; He, Xijing; Zhou, Jinsong; Li, Haopeng

    2016-09-01

    Cannabidiol, a major component of marijuana, protects nerves, and exerts antispasmodic, anti-inflammatory and anti‑anxiety effects. In the current study, the protective effect of cannabidiol was observed to prevent hydrogen peroxide (H2O2)‑induced apoptosis, inflammation and oxidative stress in nucleus pulposus cells. Nucleus pulposus cells were isolated from rats and cultured in vitro, and H2O2 was used to construct the nucleus pulposus cell model. Cell viability of the nucleus pulposus cells was assessed using a 3‑(4,5-dimethylthiazol-2-yl)-2,5‑diphenyltetrazolium bromide assay. The ratio of apoptotic cells, and caspase‑3 or cyclooxygenase‑2 (COX‑2) mRNA expression was analyzed by annexin V‑fluorescein isothiocyanate/propidium‑iodide staining and reverse transcription‑quantitative polymerase chain reaction, respectively. The quantities of interleukin (IL)‑1β and interleukin‑6 were measured using a series of assay kits. B-cell lymphoma 2 (Bcl‑2) and inducible nitric oxide synthase (iNOS) protein expression levels were analyzed using western blotting. The present study identified that cannabidiol enhanced cell viability and reduced apoptosis in H2O2‑treated nucleus pulposus cells in vitro using a lumbar disc herniation (LDH) model. In addition, cannabidiol reduced caspase‑3 gene expression and augmented the Bcl‑2 protein expression levels in the nucleus pulposus cells following H2O2 exposure. Pre‑treatment with cannabidiol suppressed the promotion of COX‑2, iNOS, IL‑1β and IL‑6 expression in the nucleus pulposus cells following H2O2 exposure. Taken together, these results suggest that cannabidiol potentially exerts its protective effect on LDH via the suppression of anti‑apoptosis, anti‑inflammation and anti‑oxidative activities in nucleus pulposus cells. PMID:27430346

  16. 77 FR 72884 - Crystalline Silicon Photovoltaic Cells and Modules From China

    Science.gov (United States)

    2012-12-06

    ... COMMISSION Crystalline Silicon Photovoltaic Cells and Modules From China Determinations On the basis of the... reason of imports of crystalline silicon photovoltaic cells and modules from China, provided for in... silicon photovoltaic cells and modules from China. Chairman Irving A. Williamson and Commissioner Dean...

  17. Characteristic of endocrine cells of rat small intestine after administration of cryopreserved placenta on the background of acute aseptic peritoneal inflammation

    Directory of Open Access Journals (Sweden)

    Shepitko K.V.

    2015-06-01

    Full Text Available Background. Modern conceptions about mechanisms of inflammation of the small intestine could not be formed without an understanding of intercellular relationships that are realized by biologically active signaling molecules produced by endocrine cells. Methods. The experimental study has been carried out on the small intestine extracted from 140 adult male rats. Electron and light microscopy methods were used. Acute aseptic inflammation was modeled by intraperitoneal carrageenan injection; influence of subcutaneously cryopreserved placenta injection was analyzed. Results. After modeling of the acute aseptic peritoneal inflammation the maximal increase of ECL-cells was noted on the 21st day. The slowest restoration of endocrine cells number occurred on all measured parameters and was observed on day 30th of the observation. In case of administration of cryopreserved placenta at the early stages (days 3rd – 7th the increase of average number of EC- and ECL-cells promoted the enhanced permeability of vessels in the lamina propria. The decrease in number of P-cells prevented the development of hyperacid gastritis. Reduction in the average number of D1- cells prevented the excessive vasodilatation and facilitated the excretion of excess fluid from the foci of inflammation. In simultaneous subcutaneous administration of cryopreserved placenta and modeling of acute aseptic peritoneal inflammation the number of ЕС- and ЕСL-cells increased, accelerating the vascular response to inflammation. Conclusion. Active appearance of low-differentiated cells including those with “shapes of mitosis” on the day 14th indicates restoration of structural components of the small intestine mucosa and processes of absorption and parietal digestion after placenta administration during acute aseptic inflammation. Citation: Shepitko KV. [Characteristic of endocrine cells of rat small intestine after administration of cryopreserved placenta on the background of

  18. Hypoxia modulates infection of epithelial cells by Pseudomonas aeruginosa.

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    Bettina Schaible

    Full Text Available Pseudomonas aeruginosa (P. aeruginosa is an opportunistic pathogen commonly associated with lung and wound infections. Hypoxia is a frequent feature of the microenvironment of infected tissues which induces the expression of genes associated with innate immunity and inflammation in host cells primarily through the activation of the hypoxia-inducible factor (HIF and Nuclear factor kappaB (NF-κB pathways which are regulated by oxygen-dependent prolyl-hydroxylases. Hypoxia also affects virulence and antibiotic resistance in bacterial pathogens. However, less is known about the impact of hypoxia on host-pathogen interactions such as bacterial adhesion and infection. In the current study, we demonstrate that hypoxia decreases the internalization of P. aeruginosa into cultured epithelial cells resulting in decreased host cell death. This response can also be elicited by the hydroxylase inhibitor Dimethyloxallyl Glycine (DMOG. Reducing HIF-2α expression or Rho kinase activity diminished the effects of hypoxia on P. aeruginosa infection. Furthermore, in an in vivo pneumonia infection model, application of DMOG 48 h before infection with P. aeruginosa significantly reduced mortality. Thus, hypoxia reduces P. aeruginosa internalization into epithelial cells and pharmacologic manipulation of the host pathways involved may represent new therapeutic targets in the treatment of P. aeruginosa infection.

  19. Nitric oxide-induced oxidative stress impairs pacemaker function of murine interstitial cells of Cajal during inflammation.

    Science.gov (United States)

    Kaji, Noriyuki; Horiguchi, Kazuhide; Iino, Satoshi; Nakayama, Shinsuke; Ohwada, Tomohiko; Otani, Yuko; Firman; Murata, Takahisa; Sanders, Kenton M; Ozaki, Hiroshi; Hori, Masatoshi

    2016-09-01

    The pacemaker function of interstitial cells of Cajal (ICC) is impaired during intestinal inflammation. The aim of this study is to clarify the pathophysiological mechanisms of ICC dysfunction during inflammatory condition by using intestinal cell clusters. Cell clusters were prepared from smooth muscle layer of murine jejunum and treated with interferon-gamma and lipopolysaccharide (IFN-γ+LPS) for 24h to induce inflammation. Pacemaker function of ICC was monitored by measuring cytosolic Ca(2+) oscillation in the presence of nifedipine. Treatment with IFN-γ+LPS impaired the pacemaker activity of ICC with increasing mRNA level of interleukin-1 beta, tumor necrosis factor-alpha and interleukin-6 in cell clusters; however, treatment with these cytokines individually had little effect on pacemaker activity of ICC. Treatment with IFN-γ+LPS also induced the expression of inducible nitric oxide synthase (iNOS) in smooth muscle cells and resident macrophages, but not in ICC. Pretreatment with NOS inhibitor, L-NAME or iNOS inhibitor, 1400W ameliorated IFN-γ+LPS-induced pacemaker dysfunction of ICC. Pretreatment with guanylate cyclase inhibitor, ODQ did not, but antioxidant, apocynin, to suppress NO-induced oxidative stress, significantly suppressed the impairment of ICC function induced by IFN-γ+LPS. Treatment with IFN-γ+LPS also decreased c-Kit-positive ICC, which was prevented by pretreatment with L-NAME. However, apoptotic ICC were not detected in IFN-γ+LPS-treated clusters, suggesting IFN-γ+LPS stimulation just changed the phenotype of ICC but not induced cell death. Moreover, ultrastructure of ICC was not disturbed by IFN-γ+LPS. In conclusion, ICC dysfunction during inflammation is induced by NO-induced oxidative stress rather than NO/cGMP signaling. NO-induced oxidative stress might be the main factor to induce phenotypic changes of ICC.

  20. Effects of Tamarindus indica fruit pulp extract on abundance of HepG2 cell lysate proteins and their possible consequential impact on metabolism and inflammation.

    Science.gov (United States)

    Chong, Ursula R W; Abdul-Rahman, Puteri S; Abdul-Aziz, Azlina; Hashim, Onn H; Mat-Junit, Sarni

    2013-01-01

    The fruit pulp extract of Tamarindus indica has been reported for its antioxidant and hypolipidemic properties. In this study, the methanol extract of T. indica fruit pulp was investigated for its effects on the abundance of HepG2 cell lysate proteins. Cell lysate was extracted from HepG2 cells grown in the absence and presence of the methanol extract of T. indica fruit pulp. Approximately 2500 spots were resolved using two-dimensional gel electrophoresis and the abundance of 20 cellular proteins was found to be significantly reduced. Among the proteins of reduced abundance, fourteen, including six proteins involved in metabolism (including ethanolamine phosphate cytidylyltransferase), four mitochondrial proteins (including prohibitin and respiratory chain proteins), and four proteins involved in translation and splicing, were positively identified by mass spectrometry and database search. The identified HepG2 altered abundance proteins, when taken together and analyzed by Ingenuity Pathways Analysis (IPA) software, are suggestive of the effects of T. indica fruit pulp extract on metabolism and inflammation, which are modulated by LXR/RXR. In conclusion, the methanol fruit pulp extract of T. indica was shown to cause reduced abundance of HepG2 mitochondrial, metabolic, and regulatory proteins involved in oxidative phosphorylation, protein synthesis, and cellular metabolism.

  1. Effects of Tamarindus indica Fruit Pulp Extract on Abundance of HepG2 Cell Lysate Proteins and Their Possible Consequential Impact on Metabolism and Inflammation

    Directory of Open Access Journals (Sweden)

    Ursula R. W. Chong

    2013-01-01

    Full Text Available The fruit pulp extract of Tamarindus indica has been reported for its antioxidant and hypolipidemic properties. In this study, the methanol extract of T. indica fruit pulp was investigated for its effects on the abundance of HepG2 cell lysate proteins. Cell lysate was extracted from HepG2 cells grown in the absence and presence of the methanol extract of T. indica fruit pulp. Approximately 2500 spots were resolved using two-dimensional gel electrophoresis and the abundance of 20 cellular proteins was found to be significantly reduced. Among the proteins of reduced abundance, fourteen, including six proteins involved in metabolism (including ethanolamine phosphate cytidylyltransferase, four mitochondrial proteins (including prohibitin and respiratory chain proteins, and four proteins involved in translation and splicing, were positively identified by mass spectrometry and database search. The identified HepG2 altered abundance proteins, when taken together and analyzed by Ingenuity Pathways Analysis (IPA software, are suggestive of the effects of T. indica fruit pulp extract on metabolism and inflammation, which are modulated by LXR/RXR. In conclusion, the methanol fruit pulp extract of T. indica was shown to cause reduced abundance of HepG2 mitochondrial, metabolic, and regulatory proteins involved in oxidative phosphorylation, protein synthesis, and cellular metabolism.

  2. Human mesenchymal stem cells resolve airway inflammation, hyperreactivity, and histopathology in a mouse model of occupational asthma.

    Science.gov (United States)

    Martínez-González, Itziar; Cruz, Maria-Jesús; Moreno, Rafael; Morell, Ferran; Muñoz, Xavier; Aran, Josep M

    2014-10-01

    Occupational asthma (OA) is characterized by allergic airway inflammation and hyperresponsiveness, leading to progressive airway remodeling and a concomitant decline in lung function. The management of OA remains suboptimal in clinical practice. Thus, establishing effective therapies might overcome the natural history of the disease. We evaluated the ability of human adipose-tissue-derived mesenchymal stem cells (hASCs), either unmodified or engineered to secrete the IL-33 decoy receptor sST2, to attenuate the inflammatory and respiratory symptoms in a previously validated mouse model of OA to ammonium persulfate (AP). Twenty-four hours after a dermal AP sensitization and intranasal challenge regimen, the animals received intravenously 1 × 10(6) cells (either hASCs or hASCs overexpressing sST2) or saline and were analyzed at 1, 3, and 6 days after treatment. The infused hASCs induced an anti-inflammatory and restorative program upon reaching the AP-injured, asthmatic lungs, leading to early reduction of neutrophilic inflammation and total IgE production, preserved alveolar architecture with nearly absent lymphoplasmacytic infiltrates, negligible smooth muscle hyperplasia/hypertrophy in the peribronchiolar areas, and baseline airway hyperreactivity (AHR) to methacholine. Local sST2 overexpression barely increased the substantial efficacy displayed by unmodified hASCs. Thus, hASCs may represent a viable multiaction therapeutic capable to adequately respond to the AP-injured lung environment by resolving inflammation, tissue remodeling, and bronchial hyperresponsiveness typical of OA. PMID:24798370

  3. Intradialytic aerobic cycling exercise alleviates inflammation and improves endothelial progenitor cell count and bone density in hemodialysis patients.

    Science.gov (United States)

    Liao, Min-Tser; Liu, Wen-Chih; Lin, Fu-Huang; Huang, Ching-Feng; Chen, Shao-Yuan; Liu, Chuan-Chieh; Lin, Shih-Hua; Lu, Kuo-Cheng; Wu, Chia-Chao

    2016-07-01

    Inflammation, endothelial dysfunction, and mineral bone disease are critical factors contributing to morbidity and mortality in hemodialysis (HD) patients. Physical exercise alleviates inflammation and increases bone density. Here, we investigated the effects of intradialytic aerobic cycling exercise on HD patients. Forty end-stage renal disease patients undergoing HD were randomly assigned to either an exercise or control group. The patients in the exercise group performed a cycling program consisting of a 5-minute warm-up, 20 minutes of cycling at the desired workload, and a 5-minute cool down during 3 HD sessions per week for 3 months. Biochemical markers, inflammatory cytokines, nutritional status, the serum endothelial progenitor cell (EPC) count, bone mineral density, and functional capacity were analyzed. After 3 months of exercise, the patients in the exercise group showed significant improvements in serum albumin levels, the body mass index, inflammatory cytokine levels, and the number of cells positive for CD133, CD34, and kinase insert domain-conjugating receptor. Compared with the exercise group, the patients in the control group showed a loss of bone density at the femoral neck and no increases in EPCs. The patients in the exercise group also had a significantly greater 6-minute walk distance after completing the exercise program. Furthermore, the number of EPCs significantly correlated with the 6-minute walk distance both before and after the 3-month program. Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition, bone mineral density, and exercise tolerance in HD patients. PMID:27399127

  4. Novel immune modulators used in hematology: impact on NK cells.

    Science.gov (United States)

    Krieg, Stephanie; Ullrich, Evelyn

    2012-01-01

    There is a wide range of important pharmaceuticals used in treatment of cancer. Besides their known effects on tumor cells, there is growing evidence for modulation of the immune system. Immunomodulatory drugs (IMiDs(®)) play an important role in the treatment of patients with multiple myeloma or myelodysplastic syndrome and have already demonstrated antitumor, anti-angiogenic, and immunostimulating effects, in particular on natural killer (NK) cells. Tyrosine kinase inhibitors are directly targeting different kinases and are known to regulate effector NK cells and expression of NKG2D ligands (NKG2DLs) on tumor cells. Demethylating agents, histone deacetylases, and proteasome inhibitors interfere with the epigenetic regulation and protein degradation of malignant cells. There are first hints that these drugs also sensitize tumor cells to chemotherapy, radiation, and NK cell-mediated cytotoxicity by enhanced expression of TRAIL and NKG2DLs. However, these pharmaceuticals may also impair NK cell function in a dose- and time-dependent manner. In summary, this review provides an update on the effects of different novel molecules on the immune system focusing NK cells. PMID:23316191

  5. HLA‐G modulates the radiosensitivity of human neoplastic cells

    International Nuclear Information System (INIS)

    Tumor cells show a very broad range of radiosensitivities. The differential radiosensitivity may depend on many factors, being the efficiency to recognize and/or repair the DNA lesion, and the cell cycle control mechanisms, the most important (Jeggo and Lavin, 2009; Kumala et al., 2003). Human leukocyte antigen‐G (HLA‐G) is a non‐classical HLA class I molecule involved in fetus protection form the maternal immune system, transplant tolerance, and viral and tumoral immune escape (Carosella et al., 2008). It has been determined that gamma radiation modulates HLA‐G expression at the plasma membrane of human melanoma cells. However, its role in tumoral radiosensitivity has not been demonstrated yet. The objective of this work was to determine if the radiosensitivity of human neoplastic cell lines cultured in vitro was mediated by HLA‐G expression. (authors)

  6. Retroperitoneal inflammation

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001255.htm Retroperitoneal inflammation To use the sharing features on this page, please enable JavaScript. Retroperitoneal inflammation is swelling that occurs in the retroperitoneal space. ...

  7. Effect of Chicoric Acid on Mast Cell-Mediated Allergic Inflammation in Vitro and in Vivo.

    Science.gov (United States)

    Lee, Na Young; Chung, Kyung-Sook; Jin, Jong Sik; Bang, Keuk Soo; Eom, Ye-Jin; Hong, Chul-Hee; Nugroho, Agung; Park, Hee-Jun; An, Hyo-Jin

    2015-12-24

    Chicoric acid (dicaffeoyl-tartaric acid), is a natural phenolic compound found in a number of plants, such as chicory (Cichorium intybus) and Echinacea (Echinacea purpurea), which possesses antioxidant, anti-inflammatory, antiviral, and analgesic activities. Although these biological effects of chicoric acid have been investigated, there are no reports of its antiallergic-related anti-inflammatory effects in human mast cells (HMC)-1 or anaphylactic activity in a mouse model. Therefore, we investigated the antiallergic-related anti-inflammatory effect of chicoric acid and its underlying mechanisms of action using phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated HMC-1 cells. Chicoric acid decreased the mRNA expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. We studied the inhibitory effects of chicoric acid on the nuclear translocation of nuclear factor kappa B (NF-κB) and activation of caspase-1. However, mitogen-activated protein kinase (MAPK) activation was not sufficient to abrogate the stimulus. In addition, we investigated the ability of chicoric acid to inhibit compound 48/80-induced systemic anaphylaxis in vivo. Oral administration of chicoric acid at 20 mg/kg inhibited histamine release and protected mice against compound 48/80-induced anaphylactic mortality. These results suggest that chicoric acid has an antiallergic-related anti-inflammatory effect that involves modulating mast cell-mediated allergic responses. Therefore, chicoric acid could be an efficacious agent for allergy-related inflammatory disorders. PMID:26593037

  8. Autocrine regulation of pulmonary inflammation by effector T-cell derived IL-10 during infection with respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Jie Sun

    2011-08-01

    Full Text Available Respiratory syncytial virus (RSV infection is the leading viral cause of severe lower respiratory tract illness in young infants. Clinical studies have documented that certain polymorphisms in the gene encoding the regulatory cytokine IL-10 are associated with the development of severe bronchiolitis in RSV infected infants. Here, we examined the role of IL-10 in a murine model of primary RSV infection and found that high levels of IL-10 are produced in the respiratory tract by anti-viral effector T cells at the onset of the adaptive immune response. We demonstrated that the function of the effector T cell -derived IL-10 in vivo is to limit the excess pulmonary inflammation and thereby to maintain critical lung function. We further identify a novel mechanism by which effector T cell-derived IL-10 controls excess inflammation by feedback inhibition through engagement of the IL-10 receptor on the antiviral effector T cells. Our findings suggest a potentially critical role of effector T cell-derived IL-10 in controlling disease severity in clinical RSV infection.

  9. Effect of bone marrow derived mesenchymal stem cells on lung pathology and inflammation in ovalbumin-induced asthma in mouse

    Directory of Open Access Journals (Sweden)

    Maryam Mohammadian

    2016-01-01

    Full Text Available Objective(s:Bone marrow-derived mesenchymal stem cells (BMSCs have attracted significant interest to treat asthma and its complication. In this study, the effects of BMSCs on lung pathology and inflammation in an ovalbumin-induced asthma model in mouse were examined. Materials and Methods:BALB/c mice were divided into three groups: control group (animals were not sensitized, asthma group (animals were sensitized by ovalbumin, asthma+BMSC group (animals were sensitized by ovalbumin and treated with BMSCs. BMSCs were isolated and characterized and then labeled with Bromodeoxyuridine (BrdU. After that the cells transferred into asthmatic mice. Histopathological changes of the airways, BMSCs migration and total and differential white blood cell (WBC count in bronchoalveolar lavage (BAL fluid were evaluated. Results:A large number of BrdU-BMSCs were found in the lungs of mice treated with BMSCs. The histopathological changes, BAL total WBC counts and the percentage of neutrophils and eosinophils were increased in asthma group compared to the control group. Treatment with BMSCs significantly decreased airway pathological indices, inflammatory cell infiltration, and also goblet cell hyperplasia. Conclusion:The results of this study revealed that BMSCs therapy significantly suppressed the lung pathology and inflammation in the ovalbumin induced asthma model in mouse.

  10. The POZ-ZF transcription factor Kaiso (ZBTB33 induces inflammation and progenitor cell differentiation in the murine intestine.

    Directory of Open Access Journals (Sweden)

    Roopali Chaudhary

    Full Text Available Since its discovery, several studies have implicated the POZ-ZF protein Kaiso in both developmental and tumorigenic processes. However, most of the information regarding Kaiso's function to date has been gleaned from studies in Xenopus laevis embryos and mammalian cultured cells. To examine Kaiso's role in a relevant, mammalian organ-specific context, we generated and characterized a Kaiso transgenic mouse expressing a murine Kaiso transgene under the control of the intestine-specific villin promoter. Kaiso transgenic mice were viable and fertile but pathological examination of the small intestine revealed distinct morphological changes. Kaiso transgenics (Kaiso(Tg/+ exhibited a crypt expansion phenotype that was accompanied by increased differentiation of epithelial progenitor cells into secretory cell lineages; this was evidenced by increased cell populations expressing Goblet, Paneth and enteroendocrine markers. Paradoxically however, enhanced differentiation in Kaiso(Tg/+ was accompanied by reduced proliferation, a phenotype reminiscent of Notch inhibition. Indeed, expression of the Notch signalling target HES-1 was decreased in Kaiso(Tg/+ animals. Finally, our Kaiso transgenics exhibited several hallmarks of inflammation, including increased neutrophil infiltration and activation, villi fusion and crypt hyperplasia. Interestingly, the Kaiso binding partner and emerging anti-inflammatory mediator p120(ctn is recruited to the nucleus in Kaiso(Tg/+ mice intestinal cells suggesting that Kaiso may elicit inflammation by antagonizing p120(ctn function.

  11. Uric acid: a modulator of prostate cells and activin sensitivity.

    Science.gov (United States)

    Sangkop, Febbie; Singh, Geeta; Rodrigues, Ely; Gold, Elspeth; Bahn, Andrew

    2016-03-01

    Elevated serum uric acid (SUA) or urate is associated with inflammation and gout. Recent evidence has linked urate to cancers, but little is known about urate effects in prostate cancer. Activins are inflammatory cytokines and negative growth regulators in the prostate. A hallmark of prostate cancer progression is activin insensitivity; however, mechanisms underlying this are unclear. We propose that elevated SUA is associated with prostate cancer counteracting the growth inhibitory effects of activins. The expression of activins A and B, urate transporter GLUT9 and tissue urate levels were examined in human prostate disease. Intracellular and secreted urate and GLUT9 expression were assessed in human prostate cancer cell lines. Furthermore, the effects of urate and probenecid, a known urate transport inhibitor, were determined in combination with activin A. Activin A expression was increased in low-grade prostate cancer, whereas activin B expression was reduced in high-grade prostate cancer. Intracellular urate levels decreased in all prostate pathologies, while GLUT9 expression decreased in benign prostatic hyperplasia, prostatitis and high-grade prostate cancer. Activin responsive LNCaP cells had higher intracellular and lower secreted urate levels than activin-insensitive PC3 cells. GLUT9 expression in prostate cancer cells was progressively lower than in prostate epithelial cells. Elevated extracellular urate was growth promoting in vitro, which was abolished by the gout medication probenecid, and it antagonized the growth inhibitory effects of activins. This study shows for the first time that a change in plasma or intracellular urate levels, possibly involving GLUT9 and a urate efflux transporter, has an impact on prostate cancer cell growth, and that lowering SUA levels in prostate cancer is likely to be therapeutically beneficial. PMID:26910779

  12. Yeast modulation of human dendritic cell cytokine secretion: an in vitro study.

    Directory of Open Access Journals (Sweden)

    Ida M Smith

    Full Text Available Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The concept of individual microorganisms influencing the makeup of T cell subsets via interactions with intestinal dendritic cells (DCs appears to constitute the foundation for immunoregulatory effects of probiotics, and several studies have reported probiotic strains resulting in reduction of intestinal inflammation through modulation of DC function. Consequent to a focus on Saccharomyces boulardii as the fundamental probiotic yeast, very little is known about hundreds of non-Saccharomyces yeasts in terms of their interaction with the human gastrointestinal immune system. The aim of the present study was to evaluate 170 yeast strains representing 75 diverse species for modulation of inflammatory cytokine secretion by human DCs in vitro, as compared to cytokine responses induced by a S. boulardii reference strain with probiotic properties documented in clinical trials. Furthermore, we investigated whether cytokine inducing interactions between yeasts and human DCs are dependent upon yeast viability or rather a product of membrane interactions regardless of yeast metabolic function. We demonstrate high diversity in yeast induced cytokine profiles and employ multivariate data analysis to reveal distinct clustering of yeasts inducing similar cytokine profiles in DCs, highlighting clear species distinction within specific yeast genera. The observed differences in induced DC cytokine profiles add to the currently very limited knowledge of the cross-talk between yeasts and human immune cells and provide a foundation for selecting yeast strains for further characterization and development toward potentially novel yeast probiotics. Additionally, we present data to support a hypothesis that the interaction between yeasts and human DCs does not solely depend on yeast viability, a concept which may suggest a need for further classifications

  13. Research on polycrystalline thin-film materials, cells, and modules

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, R.L.; Zweibel, K.; Ullal, H.S.

    1990-11-01

    The US Department of Energy (DOE) supports research activities in polycrystalline thin films through the Polycrystalline Thin-Film Program at the Solar Energy Research Institute (SERI). This program includes research and development (R D) in both copper indium diselenide and cadmium telluride thin films for photovoltaic applications. The objective of this program is to support R D of photovoltaic cells and modules that meet the DOE long-term goals of high efficiency (15%--20%), low cost ($50/m{sup 2}), and reliability (30-year life time). Research carried out in this area is receiving increased recognition due to important advances in polycrystalline thin-film CuInSe{sub 2} and CdTe solar cells and modules. These have become the leading thin-film materials for photovoltaics in terms of efficiency and stability. DOE has recognized this potential through a competitive initiative for the development of CuInSe{sub 2} and CdTe modules. This paper focuses on the recent progress and future directions of the Polycrystalline Thin-Film Program and the status of the subcontracted research on these promising photovoltaic materials. 26 refs., 12 figs, 1 tab.

  14. Research on polycrystalline thin-film materials, cells, and modules

    Science.gov (United States)

    Mitchell, R. L.; Zweibel, K.; Ullal, H. S.

    1990-11-01

    DOE supports research activities in polycrystalline thin films through the Polycrystalline Thin Film Program. This program includes includes R and D in both copper indium diselenide and cadmium telluride thin films for photovoltaic applications. The objective is to support R and D of photovoltaic cells and modules that meet the DOE long term goals of high efficiency (15 to 20 percent), low cost ($50/sq cm), and reliability (30-year life time). Research carried out in this area is receiving increased recognition due to important advances in polycrystalline thin film CuInSe2 and CdTe solar cells and modules. These have become the leading thin film materials for photovoltaics in terms of efficiency and stability. DOE has recognized this potential through a competitive initiative for the development of CuInSe(sub 2) and CdTe modules. The recent progress and future directions are studied of the Polycrystalline Thin Film Program and the status of the subcontracted research on these promising photovoltaic materials.

  15. Plasmacytoid dendritic cell-derived IFNα modulates Th17 differentiation during early Bordetella pertussis infection in mice.

    Science.gov (United States)

    Wu, V; Smith, A A; You, H; Nguyen, T A; Ferguson, R; Taylor, M; Park, J E; Llontop, P; Youngman, K R; Abramson, T

    2016-05-01

    Whooping cough is a highly contagious respiratory disease caused by Bordetella pertussis (B. pertussis). T helper 17 (Th17) cells have a central role in the resolution of the infection. Emerging studies document that type I interferons (IFNs) suppress Th17 differentiation and interleukin (IL)-17 responses in models of infection and chronic inflammation. As plasmacytoid dendritic cells (pDCs) are a major source of type I IFNs, we hypothesize that during B. pertussis infection in mice, pDC-derived IFNα inhibits a rapid increase in Th17 cells. We found that IFNα-secreting pDCs appear in the lungs during the early stages of infection, while a robust rise of Th17 cells in the lungs is detected at 15 days post-infection or later. The presence of IFNα led to reduced Th17 differentiation and proliferation in vitro. Furthermore, in vivo blocking of IFNα produced by pDCs during infection with B. pertussis infection resulted in early increase of Th17 frequency, inflammation, and reduced bacterial loads in the airways of infected mice. Taken together, the experiments reported here describe an inhibitory role for pDCs and pDC-derived IFNα in modulating Th17 responses during the early stages of B. pertussis infection, which may explain the prolonged nature of whooping cough.

  16. PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid-Derived Suppressor Cells during Pneumococcal Pneumonia.

    Science.gov (United States)

    Walker, Melissa M; Novak, Lea; Widener, Rebecca; Grubbs, James Aaron; King, Janice; Hale, Joanetha Y; Ochs, Martina M; Myers, Lisa E; Briles, David E; Deshane, Jessy

    2016-03-01

    We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, bronchoalveolar lavage, and spleens of mice at 24 h postinfection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12 h) in the focal pneumonia model, which lacks bacteremia or sepsis. Histologica