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https://hdl.handle.net/2440/7466
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Type: | Journal article |
Title: | Altered responses of human macrophages to lipopolysaccharide by hydroperoxy eicosatetraenoic acid, hydroxy eicosatetraenoic acid, and arachidonic acid. Inhibition of tumor necrosis factor production |
Author: | Ferrante, J. Huang, Z. Nandoskar, M. Hii, C. Robinson, B. Rathjen, D. Poulos, A. Morris, C. Ferrante, A. |
Citation: | Journal of Clinical Investigation, 1997; 99(6):1445-1452 |
Publisher: | ROCKEFELLER UNIV PRESS |
Issue Date: | 1997 |
ISSN: | 0021-9738 1558-8238 |
Statement of Responsibility: | J V Ferrante, Z H Huang, M Nandoskar, C S Hii, B S Robinson, D A Rathjen, A Poulos, C P Morris and A Ferrante |
Abstract: | The regulation of allergic and autoimmune inflammatory reactions by polyunsaturated fatty acids and their metabolic products (eicosanoids) continues to be of major interest. Our data demonstrate that arachidonic acid 5,8,11,14-eicosatetraenoic acid (20:4n-6) and its hydroxylated derivatives 15(s)-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) and 15(s)-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) regulate agonist-induced tumor necrosis factor alpha (TNF) production, a cytokine that plays a role in inflammatory diseases. Although 20:4n-6 and 15-HETE caused a reduction in production of TNF in mononuclear leukocytes stimulated with phytohaemagglutinin, pokeweed mitogen, concanavalin A, and Staphylococcus aureus, 15-HPETE was far more active. 15-HPETE was also found to dramatically depress the ability of bacterial lipopolysaccharide to induce TNF production in monocytes and the monocytic cell line Mono Mac 6. These fatty acids depressed the expression of TNF mRNA in Mono Mac 6 cells stimulated with LPS; 15-HPETE was fivefold more active than 20:4n-6 and 15-HETE. While 15-HPETE treatment neither affected LPS binding to Mono Mac 6 cells nor caused a decrease in CD14 expression, the fatty acid significantly reduced the LPS-induced translocation of PKC (translocation of alpha, betaI, betaII, and epsilon isozymes), suggesting that 15-HPETE acts by abrogating the early signal transduction events. The findings identify another molecule that could form the basis for development of antiinflammatory pharmaceuticals. |
Keywords: | Cells, Cultured Macrophages Humans Lipid Peroxides Protein Kinase C Lipopolysaccharides Fatty Acids Arachidonic Acid Hydroxyeicosatetraenoic Acids Leukotrienes Tumor Necrosis Factor-alpha Flow Cytometry Nucleic Acid Hybridization |
DOI: | 10.1172/JCI119303 |
Published version: | http://dx.doi.org/10.1172/jci119303 |
Appears in Collections: | Aurora harvest 5 Paediatrics publications |
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