Resolvin E1-induced intestinal alkaline phosphatase promotes resolution of inflammation through LPS detoxification

Eric L. Campbell, Christopher F. MacManus, Douglas J. Kominsky, Simon Keely, Louise E. Glover, Brittelle E. Bowers, Melanie Scully, Walter J. Bruyninckx, Sean P. Colgan

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Resolvin-E1 (RvE1) has been demonstrated to promote inflammatory resolution in numerous disease models. Given the importance of epithelial cells to coordination of mucosal inflammation, we hypothesized that RvE1 elicits an epithelial resolution signature. Initial studies revealed that the RvE1-receptor (ChemR23) is expressed on intestinal epithelial cells (IECs) and that microarray profiling of cells exposed to RvE1 revealed regulation of inflammatory response gene expression. Notably, RvE1 induced intestinal alkaline phosphatase (ALPI) expression and significantly enhanced epithelial ALPI enzyme activity. One role recently attributed to ALPI is the detoxification of bacterial LPS. In our studies, RvE1-exposed epithelia detoxified LPS (assessed by attenuation of NF-κB signaling). Furthermore, in epithelial-bacterial interaction assays, we determined that ALPI retarded the growth of Escherichia coli. To define these features in vivo, we used a murine dextran sulfate sodium (DSS) model of colitis. Compared with vehicle controls, administration of RvE1 resulted in significant improvement of disease activity indices (e.g., body weight, colon length) concomitant with increased ALPI expression in the intestinal epithelium. Moreover, inhibition of ALPI activity resulted in increased severity of colitis in DSS-treated animals and partially abrogated the protective influence of RvE1. Together, these data implicate a previously unappreciated role for ALPI in RvE1-mediated inflammatory resolution.

Original languageEnglish
Pages (from-to)14298-14303
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number32
DOIs
Publication statusPublished - 10 Aug 2010
Externally publishedYes

Keywords

  • Colitis
  • Endotoxin
  • Epithelia
  • Lipid mediator
  • Mucosal

ASJC Scopus subject areas

  • General

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