GW0742, a high-affinity PPAR -beta/delta agonist, inhibits acute lung injury in mice

Several lines of evidence suggest a biological role for peroxisome proliferator-activated receptor (PPAR) beta/delta in the pathogenesis of a number of diseases. The aim of this study was to investigate the effects of a high-affinity PPAR-beta/delta agonist, GW0742, in a mouse model of carrageenan (CAR)-induced pleurisy. Injection of CAR into the pleural cavity of mice elicited an acute inflammatory response characterized by accumulation of fluid containing a large number of neutrophils (polymorphonuclear leukocytes) in the pleural cavity, infiltration of polymorphonuclear leukocytes in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate, TNF-alpha and IL-1 beta. Furthermore, CAR induced lung apoptosis (Bax and Bcl-2 expression), and nitrotyrosine formation was determined by immunohistochemical analysis of lung tissues. Administration of GW0742 (0.3 mg/kg, i.p. bolus) 30 min before and 30 min after a challenge with CAR caused a reduction in all the parameters of inflammation measured. Thus, based on these findings, we propose that a PPAR-beta/delta agonist such as GW0742 may be useful in the treatment of various inflammatory diseases.