N-acetyl-L-cysteine enhances interleukin-1beta-induced nitric oxide synthase expression.
N-acetyl-L-cysteine enhances interleukin-1beta-induced nitric oxide synthase expression.
复制标题
DOI：
10.1161/01.hyp.34.4.574
复制
发表时间：
1999-10
期刊：
影响因子：
8.3
通讯作者：
B. Jiang;M. Haverty;P. Brecher
中科院分区：
文献类型：
--
作者：
B. Jiang;M. Haverty;P. Brecher
在大鼠血管平滑肌细胞中研究了N-乙酰-L-半胱氨酸对白细胞介素-1 β诱导的一氧化氮合酶表达的影响，以确定还原/氧化状态是否会调节精氨酸诱导的变化。白细胞介素-1 β以时间和剂量依赖性方式诱导亚硝酸盐的产生，亚硝酸盐是一氧化氮的稳定代谢产物。加入N-乙酰-L-半胱氨酸以剂量依赖性方式增强细胞因子诱导的亚硝酸盐产生，加入1 mmol/L N-乙酰-L-半胱氨酸产生>50%的增加。当细胞单独用N-乙酰-L-半胱氨酸处理时，对亚硝酸盐的产生没有影响。北方和Western印迹分析显示，N-乙酰-L-半胱氨酸上调白细胞介素-1 β诱导的一氧化氮产生是由于诱导型一氧化氮合酶表达增强所致。干扰素-γ或肿瘤坏死因子-α单独使用时，在存在或不存在N-乙酰-L-半胱氨酸的情况下对亚硝酸盐的产生没有影响。与单独使用白细胞介素-1 β治疗的细胞相比，白细胞介素-1 β联合干扰素-γ或肿瘤坏死因子-α治疗的细胞亚硝酸盐积累更高。N-乙酰-L-半胱氨酸上调亚硝酸盐的产生和诱导型一氧化氮合酶的表达与白细胞介素-1 β和干扰素-γ或肿瘤坏死因子-α联合治疗诱导。然而，N-乙酰-L-半胱氨酸没有显着的影响，精氨酸诱导的核因子-κ B或信号转导和激活因子的transciption-1的激活，电泳迁移率变动分析评估。这些结果表明，N-乙酰基-L-半胱氨酸可能作为含巯基的还原剂，通过一种不依赖于核因子-kappaB或信号转导和激活剂的机制，促进细胞因子诱导大鼠血管平滑肌细胞诱导型一氧化氮合酶的表达。转录-1。
The effect of N-acetyl-L-cysteine on interleukin-1beta-induced nitric oxide synthase expression was studied in rat vascular smooth muscle cells to determine if the reduction/oxidation state would modulate cytokine-induced changes. Interleukin-1beta induced the production of nitrite, a stable metabolite of nitric oxide in a time- and dose-dependent manner. Cytokine-induced nitrite production was enhanced by the addition of N-acetyl-L-cysteine in a dose-dependent manner, with a >50% increase produced by the addition of 1 mmol/L N-acetyl-L-cysteine. There was no influence on nitrite production when the cells were treated with N-acetyl-L-cysteine alone. Northern and Western blot analyses revealed that the upregulation of interleukin-1beta-induced nitric oxide production by N-acetyl-L-cysteine resulted from an enhanced expression of inducible nitric oxide synthase. Interferon-gamma or tumor necrosis factor-alpha when used alone had no influence on nitrite production in the absence or presence of N-acetyl-L-cysteine. Nitrite accumulation was higher by the cells treated with interleukin-1beta combined with either interferon-gamma or tumor necrosis factor-alpha compared with those treated with interleukin-1beta alone. N-Acetyl-L-cysteine upregulated nitrite production and inducible nitric oxide synthase expression induced by combination treatment with interleukin-1beta and either interferon-gamma or tumor necrosis factor-alpha. However, N-acetyl-L-cysteine had no significant influence in cytokine-induced activation of nuclear factor-kappaB or signal transducer and activator of transciption-1, as assessed by electrophoretic mobility shift assays. These results demonstrate that N-acetyl-L-cysteine possibly acted as a thiol-containing reducing agent and facilitated the expression of inducible nitric oxide synthase in rat vascular smooth muscle cells by cytokines through a mechanism that is independent of nuclear factor-kappaB or signal transducer and activator of transciption-1.