Endogenous PPARγ mediates anti-inflammatory activity in murine ischemia-reperfusion injury

Abstract

Background & Aims: Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor whose activation has been linked to several physiologic pathways including those related to the regulation of intestinal inflammation. We sought to determine whether PPARγ could function as an endogenous anti-inflammatory pathway in a murine model of intestinal ischemia-reperfusion (I/R) injury. Methods: PPARγ-deficient and wild-type mice were examined for their response to I/R procedure. Treatment with a PPARγ-specific ligand was also performed. Results: In a murine model of intestinal I/R injury, we observed more severe injury in PPARγ-deficient mice and protection against local and remote tissue injury in mice treated with a PPARγ-activating ligand, BRL-49653. Activation of PPARγ resulted in down-regulation of intercellular adhesion molecule 1 expression by intestinal endothelium and tissue tumor necrosis factor α messenger RNA levels most likely by inhibition of the NF-κB pathway. Conclusions: These data strongly suggest that an endogenous PPARγ pathway exists in tissues that may be amenable to therapeutic manipulation in I/R-related injuries.