Oncostatin M regulates endothelin-1 production in human endothelial cells.
The effect of the macrophage- and T-lymphocyte-derived cytokine oncostatin M (OSM) on endothelin-1 (ET-1) production in cultured human umbilical cord vein endothelial cells (HUVEC) was studied. OSM (2.5-10 ng/ml) stimulated ET-1 production and the expression of preproendothelin-1 mRNA. The stimulatory effect of OSM was reversed by anti-interleukin (IL)-6 IgG (33 microg/ml). IL-6 (10 ng/ml) was shown to stimulate ET-1 production. The tyrosine kinase inhibitors herbimycin (250-500 ng/ml) and genistein (1-4 microg/ml) suppressed basal ET-1 production and reversed the stimulatory effect of OSM, whereas daidzein (1-8 microg/ml), a less active analog of genistein, had no effect on basal ET-1 production and only partly reversed the stimulatory effect of OSM. The phorbol ester phorbol 12-myristate 13-acetate (PMA) inhibited ET-1 production. Downregulation of protein kinase C (PKC) with PMA (1 microM) preincubation potentiated OSM-induced ET-1 production. In summary, OSM stimulated ET-1 production in cultured HUVEC. The stimulation was probably mediated by IL-6. Furthermore, the present data suggest that tyrosine kinase activation was involved in ET-1 stimulation and that PKC activation leads to suppression of basal and OSM-stimulated ET-1 production.
Minerva Institute for Medical Research, Helsinki University Central Hospital, SF-00250 Helsinki, Finland.
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O
Saijonmaa
T
T
Nyman
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P
Pacek
F
F
Fyhrquist
D016227:Benzoquinones; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D016232:Endothelins / Q000096:biosynthesis / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D017828:Rifabutin / Q000031:analogs & derivatives; D013482:Superoxide Dismutase / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014471:Umbilical Veins
D016227:Benzoquinones; D019332:Endothelin-1; D016232:Endothelins; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D007529:Isoflavones; D047029:Lactams, Macrocyclic; C508351:OSM protein, human; D010455:Peptides; D011498:Protein Precursors; D011809:Quinones; D012333:RNA, Messenger; D053683:Oncostatin M; D017828:Rifabutin; C004742:daidzein; C020754:herbimycin; D019833:Genistein; D013482:Superoxide Dismutase; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate