Diesel exhaust particulate-induced activation of Stat3 requires activities of EGFR and Src in airway epithelial cells
Diesel exhaust particulate-induced activation of Stat3 requires activities of EGFR and Src in airway epithelial cells
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DOI：
10.1152/ajplung.00204.2006
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发表时间：
2007-02-01
影响因子：
4.9
通讯作者：
Samet, James M.
中科院分区：
文献类型：
--
作者：
Cao, Dongsun;Tal, Tamara L.;Samet, James M.
在体内，柴油机尾气颗粒物(DEP)可引起肺部的急性炎症反应，其特征是炎症细胞大量涌入和细胞因子、趋化因子等介质的表达增加。信号转导和转录激活因子(STAT)蛋白是一个细胞质转录因子家族，是响应细胞因子和生长因子刺激的关键信号转导因子。STAT家族中的一个成员，STAT3，被认为是炎症的调节因子，但还没有关于DEP暴露的研究。本研究结果表明，DEP在刺激后1h即可诱导STAT3的磷酸化，并且磷酸化的STAT3转位到细胞核内。用抑制剂PD-153035和PP2分别抑制表皮生长因子受体和Src的活性，可阻断DEP对STAT3的激活，提示DEP激活STAT3需要表皮生长因子受体和Src激酶的激活。本研究表明，DEP诱导的氧化应激可能在激活EGFR信号通路中起关键作用，抗氧化剂的预处理阻止了EGFR和STAT3的激活。这些结果表明，吸入DEP在体外可以激活促炎症信号转导通路STAT3。
In vivo exposure to diesel exhaust particles (DEP) elicits acute inflammatory responses in the lung characterized by inflammatory cell influx and elevated expression of mediators such as cytokines and chemokines. Signal transducers and activators of transcription (STAT) proteins are a family of cytoplasmic transcription factors that are key transducers of signaling in response to cytokine and growth factor stimulation. One member of the STAT family, Stat3, has been implicated as a regulator of inflammation but has not been studied in regard to DEP exposure. The results of this study show that DEP induces Stat3 phosphorylation as early as 1 h following stimulation and that phosphorylated Stat3 translocates into the nucleus. Inhibition of epidermal growth factor receptor (EGFR) and Src activities by the inhibitors PD-153035 and PP2, respectively, abolished the activation of Stat3 by DEP, suggesting that Stat3 activation by DEP requires EGFR and Src kinase activation. The present study suggests that oxidative stress induced by DEP may play a critical role in activating EGFR signaling, as evidenced by the fact that pretreatment with antioxidant prevented the activation of EGFR and Stat3. These findings demonstrate that DEP inhalation can activate proinflammatory Stat3 signaling in vitro.