Abstract
SCOPE: Colitis, an inflammatory bowel disease, is associated with aberrant regulation of the colonic mucosal immune system. Resveratrol, a natural plant product, has been found to exert anti-inflammatory properties and attenuate the development of murine colitis. In the current study, the role of microRNA (miR) in the ability of resveratrol to suppress colonic inflammation is examined. METHODS AND RESULTS: BALB/C mice with 2,4,6-Trinitrobenzenesulfonic acid solution (TNBS)-induced colitis, when treated with resveratrol, show improved clinical outcomes and reduce induction of inflammatory T cells (Th17 and Th1) while increasing CD4+Foxp3+ regulatory T cells (Tregs) and IL-10-producing CD4+ T cells. miR microarray analysis and polymerase chain reaction (PCR) validation from CD4+ T cells show treatment with resveratrol decreases the expression of several miRs (miR-31, Let7a, miR-132) that targets cytokines and transcription factors involved in anti-inflammatory T cell responses (Foxp3 and TGF-β). Transfection studies with miR-31 confirm that this miR directly regulates the expression of Foxp3. Lastly, analysis of public data from human patients with ulcerative colitis reveals that miR-31 expression is significantly increased when compared to controls. CONCLUSION: Together, the current study demonstrates that resveratrol-mediated attenuation of colitis may be regulated by miR-31 through induction of Tregs and miR-31 may serve as a therapeutic target for human colitis.