Salicylate inhibition of extracellular signal-regulated kinases and inducible nitric oxide synthase.
Salicylate inhibition of extracellular signal-regulated kinases and inducible nitric oxide synthase.
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水杨酸盐抑制细胞外信号调节激酶和诱导型一氧化氮合酶。
DOI：
10.1161/01.hyp.34.6.1259
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Brecher,P
中科院分区：
文献类型：
--
作者：
Wang,Z;Brecher,P
诱导型一氧化氮合酶（iNOS）的表达是炎症的特征性反应，可以用水杨酸钠抑制。我们使用的模型系统中，有丝分裂原活化蛋白激酶（MAPKs）的影响，可能解释水杨酸发挥其抗炎作用的机制，在心脏成纤维细胞中的精氨酸诱导的诱导型一氧化氮合酶诱导。肿瘤坏死因子-α（TNF-α）单独可快速和短暂地诱导细胞外信号调节激酶（ERK）、p38 MAPK和c-Jun N-末端激酶活性，而干扰素-γ（IFN-γ）仅可诱导ERK。选择性抑制剂抑制ERK通路或p38 MAPK活性可阻断精氨酸诱导的iNOS蛋白和亚硝酸盐的产生。水杨酸处理抑制TNF-α和IFN-γ诱导的iNOS表达，并减弱TNF-α和IFN-γ单独或联合诱导的ERK磷酸化。水杨酸对p38 MAPK和c-Jun N-末端激酶的激活无明显影响。结果表明，水杨酸能剂量依赖性地抑制细胞因子诱导的ERK磷酸化和iNOS的表达，提示水杨酸的抗炎作用部分是通过抑制ERK通路和iNOS的诱导而发挥的。
—The expression of inducible nitric oxide synthase (iNOS) is a characteristic response to inflammation and can be inhibited with sodium salicylate. We used the cytokine-induced iNOS induction in cardiac fibroblasts as a model system in which to test the hypothesis that effects on mitogen-activated protein kinases (MAPKs) may explain the mechanism by which salicylate exerts its anti-inflammatory effects. Tumor necrosis factor-α (TNF-α) alone can induce extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase activity in a rapid and transient manner, whereas interferon-γ (IFN-γ) can induce only ERK. The inhibition of either the ERK pathway or p38 MAPK activity with selective inhibitors blocked cytokine-induced iNOS protein and nitrite production. Salicylate treatment inhibited iNOS expression induced by TNF-α and IFN-γ and attenuated the phosphorylation of ERK by TNF-α and IFN-γ either alone or in combination. Salicylate had no obvious effect on the activation of p38 MAPK or c-Jun N-terminal kinase. The results showed that salicylate inhibited the phosphorylation of ERK and iNOS expression induced by cytokines in a dose-dependent manner and suggested that salicylate exerts its anti-inflammatory action in part through inhibition of the ERK pathway and iNOS induction.