Nitrated oleic acid up-regulates PPARγ and attenuates experimental inflammatory bowel disease

Nitric oxide and its metabolites undergo nitration reactions with unsaturated fatty acids during oxidative Inflammatory conditions, forming electrophilic nitro-fatty acid derivatives. These endogenous electrophilic mediators activate anti-inflammatory signaling reactions, serving as high-affinity ligands for peroxisome proliferator-activated receptor gamma (PPAR gamma). Here we examined the therapeutic effects of 9- or 10-nitrooctadecenoic oleic acid (OA-NO2) and native oleic acid (OA) in a mouse model of colitis OA-NO2 seduced the disease activity index and completely prevented dextran sulfate sodium-induced colon shortening and the increase in colonic p65 expression Increased PPAR gamma expression was observed in colon samples as well as in cells after OA-NO2 administration, whereas no effect was seen with OA This induction of hPAR gamma expression was completely abolished by the PPAR gamma antagonist CW9662 5-Aminosalicylic acid. an anti-inflammatory drug routinely used in the management of inflammatory bowel disease, also increased PPAR gamma expression but to a lesser extent Altogether. these findings demonstrate that administration of OA-NO2 attenuates colonic inflammation and improves clinical symptoms in experimental inflammatory bowel disease This protection involves activation of colonic PPAR gamma. (C) 2009 Elsevier Inc All lights reserved