The role of lipoxygenases in endotoxin-induced cytokine production.
The LPS induced synthesis of tumor necrosis factor in macrophage cultures, as determined in a fibroblast cytolysis assay was found to be effectively blocked by inhibitors of lipoxygenases. Likewise, the presence of tumor necrosis factor in serum of D-galactosamine sensitized mice after challenge with endotoxin was suppressed by the lipoxygenase inhibitors. From LPS-treated macrophages 13-hydroxylinoleic acid, a lipoxygenase product was isolated, which is significantly increased after LPS treatment of the cells, covalently bound to cellular constituents and was found to counterbalance the suppression of TNF-synthesis by a lipoxygenase inhibitor when added to macrophages exogenously.
Schade
U F
UF
Forschungsinstitut Borstel, FRG.
Engel
R
R
Jakobs
D
D
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004731:Endotoxins / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D012475:Salmonella; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D014409:Tumor Necrosis Factor-alpha