[PPARgamma-gene therapy using an adenovirus vector for inflammatory bowel disease]

Peroxisome proliferator-activated receptor gamma (PPARgamma) is one of the nuclear receptors that plays a central role in adipocyte differentiation and insulin sensitivity. Recently, PPARgamma has also been recognized as a suppressive regulator of inflammation in the gastrointestinal tract. We summarize here the therapeutic benefits of PPARgamma-gene therapy using a replication-deficient adenovirus vector expressing PPARgamma (AdRGD-PPARgamma). We demonstrate that PPARgamma- protein levels are decreased in dextran sodium sulfate-induced colitis and restored in this model by intraperitoneal administration of the AdRGD-PPARgamma. Treatment with AdRGD-PPARgamma and PPARgamma-specific ligands resulted in a marked amelioration of tissue inflammation associated with the colitis, including reduction in intercellular adhesion molecule-1, cyclooxygenase-2, and tumor necrosis factor-alpha expression. Our results suggest that gene delivery of PPARgamma may open up a novel therapeutic approach for inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.