Abstract
Peroxisome proliferator-activated receptor gamma (PPARγ) is one of the nuclear receptors that plays a central role in adipocyte differentiation and insulin sensitivity. Recently, PPARγ has also been recognized as a suppressive regulator of inflammation in the gastrointestinal tract. We summarize here the therapeutic benefits of PPARγ-gene therapy using a replication-deficient adenovirus vector expressing PPARγ (AdRGD-PPARγ). We demonstrate that PPARγ- protein levels are decreased in dextran sodium sulfate-induced colitis and restored in this model by intraperitoneal administration of the AdRGD-PPARγ. Treatment with AdRGD-PPARγ and PPARγ-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 PPARγ may open up a novel therapeutic approach for inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.
