The Role of PPARγ on Restoration of Colonic Homeostasis After Experimental Stress-Induced Inflammation and Dysfunction

Background & Aims: Psychological stress has been implicated in the clinical course of several gastrointestinal diseases, but the mechanisms implicated and the effects of stress on the normal colon are not yet fully understood. Methods: Male Wistar rats were exposed to various immobilization periods as a stress paradigm. Colon was processed to assess myeloperoxidase activity, nitric oxide synthase 2, cyclooxygenase 2, and peroxisome proliferator-activated receptor gamma (PPARγ) expression and production of prostaglandins. Colonic permeability, bacterial translocation, tight junctions ultrastructure, and immunoglobulin (Ig) A levels were also evaluated. Results: Exposure to acute (6 hours) immobilization stress produced an increase in myeloperoxidase activity and nitric oxide synthase 2 and cyclooxygenase 2 expression. All these parameters remained increased after 5 days of repeated stress exposure, showing a trend to normalize after 10 days. Levels of the anti-inflammatory eicosanoid 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and expression of PPARγ run parallel with these changes. Colonic epithelial barrier was altered after stress exposure, and a significant decrease in colonic IgA levels after acute stress exposure was observed. Pretreatment with PPARγ agonists 15d-PGJ2 and rosiglitazone prevented colonic inflammation and barrier dysfunction as well as the decrease of IgA production induced after acute stress; PPARγ specific antagonist T0070907 reverted these effects. Conclusions: Activation of PPARγ in rat colon in vivo seems to counteract colonic inflammation and dysfunction induced by stress. On the other hand, PPARγ ligands may be therapeutically useful in conditions in which inflammation and barrier dysfunction takes place in colon after exposure to stress.