Resolvin E1‐induced Intestinal Alkaline Phosphatase contributes to inflammation resolution via LPS detoxification

Abstract

Inflammatory bowel diseases are disorders of unknown etiology characterized by inappropriate inflammation. There is recent intense interest in understanding mechanisms of inflammatory resolution. Resolvin‐E1 (RvE1) has been demonstrated to promote resolution in numerous disease models. Given the importance of epithelial cells in coordinating mucosal inflammation, we hypothesized that RvE1 elicits an epithelial inflammatory resolution signature.Microarray profiling of epithelial cells exposed to RvE1, revealed transcriptional induction of numerous inflammatory response genes. Notably, RvE1 induced intestinal alkaline phosphatase (ALPI) expression and enhanced epithelial ALPI enzymatic activity. ALPI was recently demonstrated to detoxify bacterial LPS. In our studies, both purified ALPI and "conditioned" LPS‐containing media derived from RvE1‐exposed epithelia were demonstrated to detoxify LPS. To define these features in vivo, we employed a murine DSS model of colitis. Compared to vehicle controls, administration of RvE1 resulted in significant improvement of disease activity indices. RvE1 treatment resulted in significantly increased ALPI expression in murine intestinal epithelial cells. Moreover, disease severity inversely correlated with ALPI expression. Taken together, these data implicate a previously unappreciated role for ALPI in RvE1 mediated inflammatory resolution.