Browsing by Author "Ghosh, Subrata"

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    Dietary n-3 PUFA May Attenuate Experimental Colitis
    (2018-02-15) Charpentier, Cloé; Chan, Ronald; Salameh, Emmeline; Mbodji, Khaly; Ueno, Aito; Coëffier, Moïse; Guérin, Charlène; Ghosh, Subrata; Savoye, Guillaume; Marion-Letellier, Rachel
    Background. Inflammatory bowel diseases (IBD) occurred in genetically predisposed people exposed to environmental triggers. Diet has long been suspected to contribute to the development of IBD. Supplementation with n-3 polyunsaturated fatty acids (PUFA) protects against intestinal inflammation in rodent models while clinical trials showed no benefits. We hypothesized that intervention timing is crucial and dietary fatty acid pattern may influence intestinal environment to modify inflammation genesis. The aim of this study was to evaluate the dietary effect of PUFA composition on intestinal inflammation. Methods. Animals received diet varying in their PUFA composition for four weeks before TNBS-induced colitis. Colon inflammatory markers and gut barrier function parameters were assessed. Inflammatory pathway PCR arrays were determined. Results. n-3 diet significantly decreased colon iNOS, COX-2 expression, IL-6 production, and LTB4 production but tended to decrease colon TNFα production () compared to control diet. Tight junction protein (claudin-1, occludin) expressions and MUC2 and TFF3 mRNA levels were not different among groups. n-9 diet also decreased colon IL-6 production (). Conclusions. Dietary n-3 PUFA influence colitis development by attenuating inflammatory markers. Further research is required to better define dietary advice with a scientific rationale.
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    Exaggerated IL-15 and Altered Expression of foxp3+ Cell-Derived Cytokines Contribute to Enhanced Colitis in Nlrp3−/− Mice
    (2016-08-17) Hirota, Simon A.; Ueno, Aito; Tulk, Sarah E.; Becker, Helen M.; Schenck, L. Patrick; Potentier, Mireille S.; Li, Yan; Ghosh, Subrata; Muruve, Daniel A.; MacDonald, Justin A.; Beck, Paul L.
    The pathogenesis of Crohn’s disease (CD) involves defects in the innate immune system, impairing responses to microbes. Studies have revealed that mutations NLRP3 are associated with CD. We reported previously that Nlrp3−/− mice were more susceptible to colitis and exhibited reduced colonic IL-10 expression. In the current study, we sought to determine how the loss of NLRP3 might be altering the function of regulatory T cells, a major source of IL-10. Colitis was induced in wild-type (WT) and Nlrp3−/− mice by treatment with dextran sulphate sodium (DSS). Lamina propria (LP) cells were assessed by flow cytometry and cytokine expression was assessed. DSS-treated Nlrp3−/− mice exhibited increased numbers of colonic foxp3+ T cells that expressed significantly lower levels of IL-10 but increased IL-17. This was associated with increased expression of colonic IL-15 and increased surface expression of IL-15 on LP dendritic cells. Neutralizing IL-15 in Nlrp3−/− mice attenuated the severity of colitis, decreased the number of colonic foxp3+ cells, and reduced the colonic expression of IL-12p40 and IL-17. These data suggest that the NLRP3 inflammasome can regulate intestinal inflammation through noncanonical mechanisms, providing additional insight as to how NLRP3 variants may contribute to the pathogenesis of CD.
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    Gene Expression Study Of Mycobacterium avium subspecies paratuberculosis Infected Cows – “A road to identify transcripts that could serve as biomarkers for early diagnosis of Johne’s disease”
    (2014-02-05) David, Joel; De Buck, Jeroen; Barkema, Herman; Ghosh, Subrata; Guan, LeLuo
    Current diagnostic tools lack sensitivity to detect JD early after infection. Hence, this study aimed to find biomarkers for early diagnosis of JD. An infection trial was set up with a high dose (n=5) and low dose (n=5) oral challenge with Mycobacterium avium subsp. paratuberculosis at 2 weeks of age and 5 non-infected control animals. Whole blood was collected at a 3-month interval (3, 6, 9, 12 and 15 months) for gene expression analysis using Affymetrix® GeneChip® Bovine Genome Array on samples obtained at 3, 6 and 9 months after infection. Microarray findings were confirmed using qPCR and longitudinal assays profiling transcripts over 15-month period was carried out. This study found differential gene expression at each sampled time point and found transcripts for potential biomarker use. CD46 was upregulated and BOLA and BNBD9-like genes were downregulated over the entire 15-months. Overall immune response was inhibited in MAP-challenged animals.
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    Postoperative complications following colectomy for ulcerative colitis: A validation study
    (BioMed Central, 2012) Kaplan, Gilaad G.; Ma, Christopher; Crespin, Marcelo; Proulx, Marie-Claude; DeSilva, Shanika; Hubbard, James; Prusinkiewicz, Martin; Nguyen, Geoffrey C; Panaccione, Remo; Ghosh, Subrata; Myers, Robert P; Quan, Hude
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    Profiling immune responses in dairy calves experimentally infected with Mycobacterium avium subsp. paratuberculosis (Map)
    (2013-09-25) Khalil, Yasmeen; De Buck, Jeroen; Ghosh, Subrata
    Johne’s disease (JD) is a debilitating chronic enteritis in ruminants caused by Mycobacterium avium subsp. paratuberculosis (Map). JD causes substantial losses to the dairy industry due to reduced milk production, fertility rates and increased culling. The control of JD is complicated by the difficult diagnosis of the disease in its early stages and low sensitivity of the current diagnostics. As Map eventually survives in the host tissue despite of aggressive immune response, our aim was to profile early Map - induced immune responses in dairy calves infected with a high or low dose of Map for a 6-month period. The circulating T-lymphocytes were profiled by their phenotypic markers and signature cytokines. Regulatory T cell markers (Foxp3, IL-10 and TGF-β) were all upregulated during the first 2 months after infection, and a shift to Th1 response with robust IFN-γ production was observed, which lasted until the end of the study. Th2 response (IL-4) was very weak during the course of this study. Upregulation of CCR9 after 6 months of infection was also observed. In conclusion, regulatory T cell response that occurs early after Map exposure is vigorous and infective dose dependent but short lived; it is then replaced by a strong Th1 response and interferon-gamma production, characteristic of subclinical JD.
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    The Effects of Smoking on Autophagy in Transformed Cell Lines and Monocyte-derived Dendritic Cells of NOD2 Genotyped Inflammatory Bowel Disease Patients
    (2016) chenoo, Shem; Ghosh, Subrata; Beck, Paul; Kaplan, Gilaad; Hirota, Simon
    Genome-wide association studies have identified around 200 genes associated with inflammatory bowel disease (IBD) among which 3 susceptible genes including NOD2, ATG16L1 and IRGM are found to increase risk of Crohn’s Disease (CD) and altering the metabolic pathway known as autophagy. The aim of this study is to look at how smoking which is detrimental in CD but beneficial to ulcerative colitis (UC) affects autophagy in both cell lines as well as primary cells. HeLa cells and THP-1 like macrophages as well as monocyte-derived dendritic cells were treated with cigarette smoke extract (CSE) which is a surrogate of smoking at different concentrations for 24h. Cells were treated with rapamycin or muramyl dipeptide (MDP) and autophagy was assessed by microscopy and Western blotting. CSE significantly inhibits autophagy in HeLa cells and THP-1 like macrophages through both the mTOR and NOD2 mediated autophagic pathways.