[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.
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D003092:Colitis / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D015212:Inflammatory Bowel Diseases / Q000628:therapy*; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors