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

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-alpha, 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.

• Authors: Makoto Arita, Masaru Yoshida, Song Hong, Eric Tjonahen, Jonathan N Glickman, Nicos A Petasis, Richard S Blumberg, Charles N Serhan
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 102 Issue 21 Pg. 7671-6 (May 24 2005) ISSN: 0027-8424 [Print] United States
• PMID: 15890784 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA Primers
• Immunoglobulin G
• Interleukin-12 Subunit p40
• Protein Subunits
• Tumor Necrosis Factor-alpha
• Interleukin-12
• Trinitrobenzenesulfonic Acid
• Eicosapentaenoic Acid
• Peroxidase
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid
• Aspirin

Topics

• Animals
• Aspirin (metabolism, therapeutic use)
• Colitis, Ulcerative (chemically induced, prevention & control)
• DNA Primers
• Eicosapentaenoic Acid (analogs & derivatives, metabolism, pharmacology, therapeutic use)
• Enzyme-Linked Immunosorbent Assay
• Female
• Gene Expression Regulation (drug effects)
• Immunoglobulin G (blood)
• Interleukin-12 (metabolism)
• Interleukin-12 Subunit p40
• Leukocytes (drug effects)
• Mice
• Mice, Inbred BALB C
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type II
• Peroxidase (metabolism)
• Protein Subunits (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Trinitrobenzenesulfonic Acid (toxicity)
• Tumor Necrosis Factor-alpha (metabolism)