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Mechanisms for anti‐inflammatory effects of 1‐[15(S)‐hydroxyeicosapentaenoyl] lysophosphatidylcholine, administered intraperitoneally, in zymosan A‐induced peritonitis
Author(s) -
Hung Nguyen Dang,
Kim Mee Ree,
Sok DaiEun
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.01117.x
Subject(s) - zymosan , inflammation , chemistry , monooxygenase , pharmacology , eicosanoid , lysophosphatidylcholine , downregulation and upregulation , biochemistry , immunology , arachidonic acid , metabolism , enzyme , biology , in vitro , cytochrome p450 , phosphatidylcholine , phospholipid , membrane , gene
BACKGROUND AND PURPOSE Lysophosphatidylcholines (lysoPCs) with polyunsaturated acyl chains are known to exert anti‐inflammatory actions. 15‐Lipoxygeanation is crucial for anti‐inflammatory action of polyunsaturated acylated lysoPCs. Here, the anti‐inflammatory actions of 1‐(15‐hydroxyeicosapentaenoyl)‐lysoPC (15‐HEPE‐lysoPC) and its derivatives were examined in a mechanistic analysis. EXPERIMENTAL APPROACH Anti‐inflammatory actions of 15‐HEPE‐lysoPC in zymosan A‐induced peritonitis of mice were examined by measuring plasma leakage and leucocyte infiltration, and determining levels of lipid mediators or cytokines. KEY RESULTS When each lysoPC, administered i.v., was assessed for its ability to suppress zymosan A‐induced plasma leakage, 15‐HEPE‐lysoPC was found to be more potent than 1‐(15‐hydroperoxyeicosapentaenoyl)‐lysoPC or 1‐eicosapentaenoyl‐lysoPC. Separately, i.p. administration of 15‐HEPE‐lysoPC markedly inhibited plasma leakage, in contrast to 15‐HEPE, which had only a small effect. 15‐HEPE‐lysoPC also decreased leucocyte infiltration. Moreover, it reduced the formation of LTC 4 and LTB 4 , 5‐lipoxygenation products, as well as the levels of pro‐inflammatory cytokines. The time‐course study indicated that 15‐HEPE‐lysoPC might participate in both the early inflammatory phase and resolution phase. Additionally, 15‐HEPE‐lysoPC administration caused a partial suppression of LTC 4 ‐induced plasma leakage and LTB 4 ‐induced leucocyte infiltration. In the metabolism study, peritoneal exudate was shown to contain lysoPC‐hydrolysing activity, crucial for anti‐inflammatory activity, and a system capable of generating lipoxin A from 15‐hydroxy eicosanoid precursor. CONCLUSIONS AND IMPLICATIONS 15‐HEPE‐lysoPC, a precursor for 15‐HEPE in target cells, induced anti‐inflammatory actions by inhibiting the formation of pro‐inflammatory leukotrienes and cytokines, and by enhancing the formation of lipoxin A. 15‐HEPE‐lysoPC might be one of many potent anti‐inflammatory lipids in vivo .