A novel therapy for colitis utilizing PPARgamma ligands to inhibit the epithelial inflammatory response

摘要

Delicately balanced mechanisms maintain the intestinal mucosa in a quiescent state of inflammation. In humans, loss of this balance leads to inflammatory bowel disease (IBD). The intestinal inflammatory phenotype observed in many immune receptor and cytokine knockout mice models lends support to the notion that cytokines help to regulate and maintain this quiescent state. More recently it has become apparent that the intestinal epithelium, which is the interface between the highly antigenic luminal environment and the mucosal immune system, itself plays an active role in the immune responsiveness of the intestinal mucosa. Intestinal epithelial cells not only express various immune receptors traditionally believed to be expressed primarily by myeloid cell lineages, but can also produce a wide array of immune modulatory substances such as cytokines and complement factors. Indeed, specific perturbation of the intestinal epithelium can lead to intestinal inflammation.