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dc.contributor.authorEpstein, Jenny
dc.description.abstractIn inflammatory bowel disease (IBD), both chronic pro-inflammatory pathways and failure of anti-inflammatory (healing) mechanisms sustain disease. The two major anti-inflammatory gut cytokines are transforming growth factor (TGF)-β and interleukin (IL)-10. Acetylation of regulatory proteins may play a role in the activation of both pathways. In IBD there is excess production of pro-inflammatory cytokines such as IL-1β and under-expression of IL-10. Fibroblasts also over-produce matrix metalloproteinases (MMP), mediating tissue destruction. Curcumin, a component of the spice turmeric and a known inhibitor of acetylation, shows clinical benefit in IBD in early trials. Objectives: To assess the anti-inflammatory effects of curcumin in the gut of children and adults with IBD. Methods: Intestinal mucosal tissue biopsies, mononuclear cells and colonic myofibroblasts from children and adults with active IBD were cultured ex vivo with curcumin. p38 MAPK, NF-κB and MMP-3 were measured by immunoblotting. IL-1β, interferon (IFN)-γ and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). Results: We have shown favourable modulation of the cytokine profile by curcumin, with enhanced IL-10 expression and decreased IL-1β, and we have demonstrated reduced p38 MAPK activation in intestinal mucosal tissue. We have also shown dose-dependent suppression of MMP-3 expression in colonic myofibroblasts (CMF) with curcumin, by a mechanism which appears to be acetylation-dependent. Conclusion: Curcumin, a naturally occurring food substance with no known human toxicity, holds promise as a novel therapy in IBD.en_US
dc.titleAcetylation: a critical factor in maintaining intestinal inflammation?en_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author

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