Regulation of 15-lipoxygenase expression by cytokines.
The arachidonate 15-lipoxygenase is induced in peripheral human monocytes by culturing the cells for 3 days in the presence of interleukin 4 (IL-4) in concentrations as low as 40 pM. Linoleic acid is oxygenated by IL-4 treated monocytes to 13(S)-hydroxy-9Z, 11E-octadecadienoic acid [13(S)-HODE] with a specific activity of about 2 nmoles 13(S)-HODE/10(6) cells min. A screening of various permanent cell lines expressing the IL-4 receptor indicated that all monocyte/macrophage lines tested did not exhibit the effect of LOX induction. However, IL-4 treatment of the lung carcinoma cell line CCC 185 and of the colon carcinoma cell line HTB 38 induces the 15-LOX as shown by activity assay and immunohistochemistry. The IL-4 mutant Y124D which has been characterized as specific IL-4 receptor antagonist in human T-cells does not induce the 15-LOX but appears to act as competitive inhibitor for the induction. Subcellular fractionation of IL-4 treated monocytes indicated a cytosolic and a membrane bound enzyme pool. The intracellular action of the LOX leads to a specific oxygenation of the membrane phospholipids which is drastically increased after damage to the cells. The possible biological role of the 15-LOX for monocyte metabolism is discussed.
Brinckmann
R
R
Institute of Biochemistry, Medical Faculty (Charité), Humboldt University, Berlin, FRG.
Kühn
H
H
D001093:Arachidonate 15-Lipoxygenase / Q000096:biosynthesis* / Q000378:metabolism; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000201:enzymology; D016207:Cytokines / Q000494:pharmacology*; D004790:Enzyme Induction; D018922:HL-60 Cells / Q000201:enzymology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008041:Linoleic Acids / Q000032:analysis; D008175:Lung Neoplasms / Q000201:enzymology; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D017354:Point Mutation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
D016207:Cytokines; D008041:Linoleic Acids; D015847:Interleukin-4; C024348:13-hydroxy-9,11-octadecadienoic acid; D001093:Arachidonate 15-Lipoxygenase