Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis

Makoto Arita, Masaru Yoshida, Song Hong, Eric Tjonahen, Jonathan N. Glickman, Nicos A. Petasis, Richard S. Blumberg, Charles N. Serhan

Research output: Contribution to journalArticle

450 Citations (Scopus)

Abstract

Resolvin E1 (RvE1; 5S, 12R, 18R-trihydroxyeicosapentaenoic acid) is an antiinflammatory lipid mediator derived from omega-3 fatty acid eicosapentaenoic acid (EPA). At the local site of inflammation, aspirin treatment enhances EPA conversion to 18R-oxygenated products, including RvE1, which carry potent antiinflammatory signals. Here, we obtained evidence for reduced leukocyte infiltration in a mouse peritonitis model, where the administration of EPA and aspirin initiated the generation of RvE1 in the exudates. Similar results were obtained with the administration of synthetic RvE1, which blocked leukocyte infiltration. RvE1 also protected against the development of 2,4,6-trinitrobenzene sulfonic acid-induced colitis. The beneficial effect was reflected by increased survival rates, sustained body weight, improvement of histologic scores, reduced serum anti-2,4,6-trinitrobenzene sulfonic acid IgG, decreased leukocyte infiltration, and proinflammatory gene expression, including IL-12 p40, TNF-α, and inducible nitric oxide synthase. Thus, the endogenous lipid mediator RvE1 counter-regulates leukocyte-mediated tissue injury and proinflammatory gene expression. These findings show an endogenous mechanism that may underlie the beneficial actions of omega-3 EPA and provide targeted approaches for the treatment of intestinal inflammation.

Original languageEnglish
Pages (from-to)7671-7676
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number21
DOIs
Publication statusPublished - 2005 May 24
Externally publishedYes

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Keywords

  • Antiinflammation
  • Aspirin-triggered lipid mediators
  • Omega-3 pufa
  • Resolvins

ASJC Scopus subject areas

  • General

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