Background & aims: 

Previous studies have demonstrated that pretreatment of mice with the heme oxygeanse (HO)-1 end product CO markedly reduces the development of postoperative ileus (POI). Recently, it was reported that CO exerts its anti-inflammatory effects through the induction of PPARg. This led us to specifically investigate the role of PPARg in the pathogenesis of POI.

Methods: 

Intestinal tissue was analyzed for gene expression, transcriptional activity, inflammatory parameters/enzyme activity, leukocyte infiltration and oxidative stress levels. Intestinal contractility and transit were evaluated by video-fluorescence imaging.

Results: 

Surgical manipulation induced a rapid phosphorylation and subsequent degradation of PPARg within both intestinal layers of the colon. Accompanying these modifications, there was a decrease in PPARg DNA-binding activity which was significantly restored by the PPARg agonist rosiglitazone. The functional severity of POI was significantly ameliorated in mice pretreated with rosiglitazone; this was associated with a down-regulation of inflammatory parameters, iNOS/COX-2 enzyme activity as well as a decrease in leukocyte recruitment into the intestinal muscularis of both colon and jejunum. These anti-inflammatory effects were preceded by a PPARg-dependent inhibition of surgically-induced Egr-1 induction. Although recent studies reported that PPARg activation can lead to up-regulation of HO-1 expression, rosiglitazone treatment partially prevented the surgically-induced HO-1 induction in our study.

Conclusions: 

These data demonstrate that PPARg occupies a key role in the pathogenesis of POI and that rosiglitazone prevents POI by suppression of the muscularis inflammatory cascade through a PPARg-dependent down-regulation of Egr-1.