1,721,191 research outputs found
Virginia Bioinformatics Institute researcher investigates impact of nutrition on human health
No full textThe Virginia Bioinformatics Institute at Virginia Tech recently welcomed its newest faculty member, Josep Bassaganya-Riera
Activation of PPARγ and δ by dietary punicic acid ameliorates intestinal inflammation in mice
No full textThe goal of the present study was to elucidate the mechanisms of immunoregulation by which dietary punicic acid (PUA) prevents or ameliorates experimental inflammatory bowel disease (IBD). The expression of PPARγ and δ, their responsive genes and pro-inflammatory cytokines was assayed in the colonic mucosa. Immune cell-specific PPARγ null, PPARδ knockout and wild-type mice were treated with PUA and challenged with 2·5 % dextran sodium sulphate (DSS). The prophylactic efficacy of PUA was examined in an IL-10− / − model of IBD. The effect of PUA on the regulatory T-cell (Treg) compartment was also examined in mice with experimental IBD. PUA ameliorated spontaneous pan-enteritis in IL-10− / − mice and DSS colitis, up-regulated Foxp3 expression in Treg and suppressed TNF-α, but the loss of functional PPARγ or δ impaired these anti-inflammatory effects. At the cellular level, the macrophage-specific deletion of PPARγ caused a complete abrogation of the protective effect of PUA, whereas the deletion of PPARδ or intestinal epithelial cell-specific PPARγ decreased its anti-inflammatory efficacy. We provide in vivo molecular evidence demonstrating that PUA ameliorates experimental IBD by regulating macrophage and T-cell function through PPARγ- and δ-dependent mechanisms.</jats:p
Punicic acid modulates mucosal immune responses and prevents gut inflammation through PPAR gamma and delta-dependent mechanisms
No full textImmunoregulatory Actions of Epithelial Cell PPAR γ at the Colonic Mucosa of Mice with Experimental Inflammatory Bowel Disease
No full textBACKGROUND: Peroxisome proliferator-activated receptors are nuclear receptors highly expressed in intestinal epithelial cells (IEC) and immune cells within the gut mucosa and are implicated in modulating inflammation and immune responses. The objective of this study was to investigate the effect of targeted deletion of PPAR gamma in IEC on progression of experimental inflammatory bowel disease (IBD). METHODOLOGY/PRINCIPAL FINDINGS: In the first phase, PPAR gamma flfl; Villin Cre- (VC-) and PPAR gamma flfl; Villin Cre+ (VC+) mice in a mixed FVB/C57BL/6 background were challenged with 2.5% dextran sodium sulfate (DSS) in drinking water for 0, 2, or 7 days. VC+ mice express a transgenic recombinase under the control of the Villin-Cre promoter that causes an IEC-specific deletion of PPAR gamma. In the second phase, we generated VC- and VC+ mice in a C57BL/6 background that were challenged with 2.5% DSS. Mice were scored on disease severity both clinically and histopathologically. Flow cytometry was used to phenotypically characterize lymphocyte and macrophage populations in blood, spleen and mesenteric lymph nodes. Global gene expression analysis was profiled using Affymetrix microarrays. The IEC-specific deficiency of PPAR gamma in mice with a mixed background worsened colonic inflammatory lesions, but had no effect on disease activity (DAI) or weight loss. In contrast, the IEC-specific PPAR gamma null mice in C57BL/6 background exhibited more severe inflammatory lesions, DAI and weight loss in comparison to their littermates expressing PPAR gamma in IEC. Global gene expression profiling revealed significantly down-regulated expression of lysosomal pathway genes and flow cytometry results demonstrated suppressed production of IL-10 by CD4+ T cells in mesenteric lymph nodes (MLN) of IEC-specific PPAR gamma null mice. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that adequate expression of PPAR gamma in IEC is required for the regulation of mucosal immune responses and prevention of experimental IBD, possibly by modulation of lysosomal and antigen presentation pathways
Differential requirements for proliferation of CD4+ and γδ+ T cells to spirochetal antigens
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Introduction to Accelerated Path to Cures and Precision Medicine in Inflammatory Bowel Disease
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