TNF-α enhances cardiac myocyte NO production through MAP kinase-mediated NF-κB activation
TNF-α enhances cardiac myocyte NO production through MAP kinase-mediated NF-κB activation
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DOI：
10.1152/ajpheart.1999.277.4.h1641
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发表时间：
1999-10-01
影响因子：
4.8
通讯作者：
Finkel, MS
中科院分区：
文献类型：
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作者：
Kan, H;Xie, ZR;Finkel, MS
我们以前报道过，白细胞介素-1 β (IL-1 β)单独诱导新生大鼠心肌细胞（CM）产生一氧化氮（NO）。肿瘤坏死因子- α (tnf - α)对诱导型NO合成酶（iNOS）的影响尚未表征。与IL-1 β不同，tnf - α单独不能增强CM中NO的产生。然而，在IL-1 β中加入tnf - α可显著增强iNOS mRNA表达、iNOS蛋白合成和NO生成（NO2-）。PD-98059阻断了tnf - α增强IL-1 β诱导的NO2-生成，PD-98059是一种选择性丝裂原活化蛋白（MAP）激酶抑制剂，但不阻断calphostin C (Cal C)，一种蛋白激酶C抑制剂。tnf - α增强的MAP激酶活性与IL-1 β刺激的nf - κ B活性增加有关。PD-98059抑制tnf - α增强的MAP激酶和nf - κ B活性，而Cal - C不抑制。因此，tnf - α增强IL-1 β诱导的NO生成与MAP激酶介导的nf - κ B激活有关。
We have previously reported that interleukin-1 beta (IL-1 beta) alone induced nitric oxide (NO) production by neonatal rat cardiac myocytes (CM). The effects of tumor necrosis factor-alpha (TNF-alpha) on inducible NO synthase (iNOS) were not characterized. Unlike IL-1 beta, TNF-alpha alone failed to enhance NO production in CM. However, the addition of TNF-alpha to IL-1 beta significantly enhanced iNOS mRNA expression, iNOS protein synthesis, and NO production (NO2-). TNF-alpha enhancement of IL-1 beta-induced NO2- production was blocked by PD-98059, a selective mitogen-activated protein (MAP) kinase kinase inhibitor, but not calphostin C (Cal C), a protein kinase C inhibitor. TNF-alpha-enhanced MAP kinase activity was associated with an increase in IL-1 beta-stimulated NF-kappa B activity. PD-98059, but not Cal C, inhibited both TNF-alpha-enhanced MAP kinase and NF-kappa B activities. Thus TNF-alpha enhancement of IL-1 beta-induced NO production is associated with MAP kinase-mediated activation of NF-kappa B.