Saijonmaa O, Nyman T, Pacek P, Fyhrquist F
Minerva Institute for Medical Research, Helsinki University Central Hospital, SF-00250 Helsinki, Finland.
Am J Physiol. 1998 Aug;275(2):H662-7. doi: 10.1152/ajpheart.1998.275.2.H662.
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.
研究了巨噬细胞和T淋巴细胞衍生的细胞因子制瘤素M（OSM）对培养的人脐静脉内皮细胞（HUVEC）中内皮素-1（ET-1）产生的影响。OSM（2.5 - 10 ng/ml）刺激ET-1的产生以及前内皮素-1 mRNA的表达。OSM的刺激作用可被抗白细胞介素（IL）-6 IgG（33 μg/ml）逆转。IL-6（10 ng/ml）被证明可刺激ET-1的产生。酪氨酸激酶抑制剂除莠霉素（250 - 500 ng/ml）和染料木黄酮（1 - 4 μg/ml）可抑制基础ET-1的产生并逆转OSM的刺激作用，而染料木黄酮活性较低的类似物大豆苷元（1 - 8 μg/ml）对基础ET-1的产生没有影响，仅部分逆转OSM的刺激作用。佛波酯佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）抑制ET-1的产生。用PMA（1 μM）预孵育下调蛋白激酶C（PKC）可增强OSM诱导的ET-1产生。总之，OSM刺激培养的HUVEC中ET-1的产生。这种刺激可能由IL-6介导。此外，目前的数据表明酪氨酸激酶激活参与了ET-1的刺激，并且PKC激活导致基础和OSM刺激的ET-1产生受到抑制。
