Acetylation: a critical factor in maintaining intestinal inflammation?
In 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.
- Theses