自分泌信号
内皮素1
肿瘤坏死因子α
旁分泌信号
生物
内分泌学
内科学
内皮素受体
血管平滑肌
内皮干细胞
内皮素
细胞因子
内皮
分子生物学
免疫学
体外
受体
医学
生物化学
平滑肌
作者
Philip A. Marsden,B. M. Brenner
出处
期刊:American Journal of Physiology-cell Physiology
[American Physiological Society]
日期:1992-04-01
卷期号:262 (4): C854-C861
被引量:267
标识
DOI:10.1152/ajpcell.1992.262.4.c854
摘要
Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), induce profound alterations in endothelial cell phenotype and are implicated in the organ dysfunction that characterizes septic shock. We explored whether TNF-alpha modulates cellular expression of endothelin-1 (ET-1). ET-1 is a potent vasoconstrictor peptide released by endothelial, vascular smooth muscle, and mesangial cells that could function as a paracrine/autocrine regulator of vascular tone and proliferation. We found that TNF-alpha induced release of ET-1 from bovine aortic endothelial cells (BAEC) in a time- and concentration-dependent manner. Rates of ET-1 release were maximal over 1-8 h and declined to, or below, baseline values after 16 h. When measured at 8 h, TNF-alpha augmented ET-1 release over the range 0.1-250 ng/ml (threshold, 0.1 ng/ml; 50% effective dose, 1.6 +/- 1.2 ng/ml; maximal effect, 100 ng/ml). The increase in secretion was accompanied by a corresponding increase in the transcriptional rate of the ET-1 gene resulting in augmented preproendothelin-1 mRNA transcript levels. TNF-alpha-stimulated increases in ET-1 gene transcription were not dependent on new protein synthesis. Actinomycin D chase experiments suggested that enhanced stability of preproendothelin-1 mRNA could not account for the increase in ET-1 transcript levels. TNF-alpha increased ET-1 release and preproendothelin-1 mRNA content in bovine renal artery and bovine glomerular capillary endothelial cells, demonstrating that the TNF-alpha effect was evident in endothelial cells derived from a variety of sources. Furthermore, augmented ET-1 expression in response to TNF-alpha was evident in bovine glomerular mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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