PPARα contributes to colonic protection in mice with DSS-induced colitis

Inflammatory bowel disease (IBD) is characterized by repeated chronic inflammation of the gastrointestinal tract. We have used the complementary model of colonic inflammation to examine the roles of peroxisome proliferator-activated receptor alpha (PPAR alpha) in colonic inflammation and thus its possible role in IBD. We characterized an innate immune-mediated model of colitis induced by dextran sulfate sodium (DSS). Mice with DSS-induced colitis were injected with Wy-14643 (2 mg/kg) as a PPAR alpha agonist every day from day 0 to day 5. We show that mice given Wy-14643 were less susceptible to experimental acute colitis induced by DSS, and this decreased susceptibility was correlated with decreased production of IFN gamma, IL-1 beta, IL-6, and TNF-alpha. Our findings suggest that PPAR alpha has a role in controlling colonic inflammation and mucosal tissue homeostasis. (c) 2010 Elsevier B.V. All rights reserved.