endothelin-1 and daidzein

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.

Topics: Benzoquinones; Cell Division; Cell Survival; Cells, Cultured; Drug Interactions; Endothelin-1; Endothelins; Endothelium, Vascular; Enzyme Inhibitors; Gene Expression Regulation; Genistein; Growth Inhibitors; Humans; Isoflavones; Lactams, Macrocyclic; Oncostatin M; Peptides; Protein Precursors; Protein-Tyrosine Kinases; Quinones; Rifabutin; RNA, Messenger; Superoxide Dismutase; Tetradecanoylphorbol Acetate; Transcription, Genetic; Umbilical Veins