477. ANGPTL4 Limits the Extent of Colonic Inflammation

Gastrointestinal disorders such as inflammatory bowel disease, colitis and enteritis share signatures of an aggravated and protracted inflammatory response. As the first line of defense, epithelial cells play an important role in secreting chemoattractants and cytokines to launch or attenuate the immune response. However, little is known about the regulation of immune responses in the gastrointestinal tract. To understand the role of colonic epithelial cells during inflammation in C57BL/6J mice, we examine the effects of dietary C18 saturated (stearic acid), unsaturated (oleic acid) fat and dextran sulfate salt (DSS) in acute colonic inflammation. Microarray analysis was conducted comparing changes in global gene expression signatures between colon samples of three treatment groups. Preliminary studies suggest that the saturated diet resulted in a colonic gene expression profile that is more closely associated to that of DSS-treated. In addition, gene ontology analyses suggest that genes that overlap between all three treatment groups are mostly involved in immunological and metabolic diseases, as well as endocrine system disorders. Further interrogation revealed that an adipokine, angiopoietin-like 4 (ANGPTL4), modulates the degree and extent of colonic inflammation. We observed an elevated inflammation status, associated with massive immune cell infiltration, in ANGPTL4−/− mice compared to its ANGPTL4+/+ littermates during DSS-induced colonic inflammation. Our preliminary studies highlights the importance of regulating the colonic expression of ANGPTL4 as an avenue to attenuate gastrointestinal inflammation.