Makoto Arita1, Masaru Yoshida1, Song Hong1, Eric Tjonahen1, Jonathan N. Glickman1, Nicos A. Petasis1, Richard S. Blumberg1, Charles N. Serhan1
1Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Gastroenterology Division, Department of Medicine, and Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; and Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, CA 90089-1661
Tóm tắt
Resolvin E1 (RvE1; 5
S
,12
R
,18
R
-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 18
R
-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.
