title: 2-Polyunsaturated acyl lysophosphatidylethanolamine attenuates inflammatory response in zymosan A-induced peritonitis in mice.
abstract: In the present study, the anti-inflammatory action of lysophosphatidylethanolamine (lysoPtdEtn), orally administered, in zymosan A-induced peritonitis was examined. Oral administration of 2-DHA-lysoPtdEtn (ED(50), ~111 μg/kg) or 2-ARA-lysoPtdEtn (ED(50), 221 μg/kg) was found to inhibit the plasma leakage in mice treated with zymosan A. In support of this, 2-polyunsaturated acyl-lysoPtdEtn diminished the formation of LTC(4), a lipid mediator responsible for vascular permeability. Next, 2-DHA-lysoPtdEtn (ED(50), 110 μg/kg) or 2-ARA-lysoPtdEtn (ED(50), 123 μg/kg) effectively inhibited the leukocyte extravasation into the peritoneum. Consistent with this, each polyunsaturated-lysoPtdEtn diminished the formation of LTB(4) and 12-HETE, potent chemotactic factors. Additionally, the level of pro-inflammatory mediator (IL-1 β, IL-6, TNF-α or NO) was lowered remarkably in contrast to the augmentation of anti-inflammatory interleukin IL-10. Furthermore, 2-(15-HETE)-lysoPtdEtn and 2-(17-HDHE)-lysoPtdEtn, 15-lipoxygenation product of 2-ARA-lysoPtdEtn and 2-DHA-lysoPtdEtn, respectively, were more potent than corresponding lysoPtdEtn, suggesting the action of 2-acyl-lysoPtdEtn might be expressed through 15-lipoxygenation. In support of this, the formation of 15-HETE and LXA(4) was upgraded in accordance with an increasing dose of 2-ARA-lysoPtdEtn. Separately, anti-inflammatory actions, 2-polyunsaturated acyl-lysoPtdEtns also drastically diminished leukocyte infiltration in a later phase of zymosan A-induced peritonitis, indicating that these lipids also possess pro-resolving activity. Taken together, it is suggested that polyunsaturated lysoPtdEtns and their lipoxygenation derivatives, could be classified as potent anti-inflammatory lipids.
authors: College of Pharmacy, Chungnam National University, Yuseoung-Gu, Daejeon, 305-764, Republic of Korea. hung_hanoi_vietnam@yahoo.com
authors: Nguyen Dang
authors: ND
authors: Hung
authors: Mee Ree
authors: MR
authors: Kim
authors: Dai-Eun
authors: DE
authors: Sok
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use*; D001093:Arachidonate 15-Lipoxygenase / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008246:Lysophospholipids / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use*; D051379:Mice; D008813:Mice, Inbred ICR; D010084:Oxidation-Reduction; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D015054:Zymosan
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016859:Lipoxygenase Inhibitors; D008246:Lysophospholipids; C008301:lysophosphatidylethanolamine; D015054:Zymosan; D001093:Arachidonate 15-Lipoxygenase