title: 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.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Song
authors.initials: S
authors.lastname: Hong
authors.forename: Eric
authors.initials: E
authors.lastname: Tjonahen
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Glickman
authors.forename: Nicos A
authors.initials: NA
authors.lastname: Petasis
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
mesh_terms: D000818:Animals; D001241:Aspirin / Q000378:metabolism* / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000139:chemically induced* / Q000517:prevention & control*; D017931:DNA Primers; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007074:Immunoglobulin G / Q000097:blood; D018664:Interleukin-12 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017931:DNA Primers; D007074:Immunoglobulin G; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D014302:Trinitrobenzenesulfonic Acid; D015118:Eicosapentaenoic Acid; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid; D001241:Aspirin