Cao Dongsun, Tal Tamara L, Graves Lee M, Gilmour Ian, Linak William, Reed William, Bromberg Philip A, Samet James M
Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
Am J Physiol Lung Cell Mol Physiol. 2007 Feb;292(2):L422-9. doi: 10.1152/ajplung.00204.2006. Epub 2006 Oct 6.
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.
体内暴露于柴油尾气颗粒（DEP）会引发肺部急性炎症反应，其特征为炎症细胞流入以及细胞因子和趋化因子等介质的表达升高。信号转导和转录激活因子（STAT）蛋白是一类细胞质转录因子，是响应细胞因子和生长因子刺激的信号传导关键转导因子。STAT家族的一个成员Stat3被认为是炎症调节因子，但尚未针对DEP暴露进行研究。本研究结果表明，DEP在刺激后1小时内即可诱导Stat3磷酸化，且磷酸化的Stat3会转位至细胞核。分别用抑制剂PD - 153035和PP2抑制表皮生长因子受体（EGFR）和Src活性，可消除DEP对Stat3的激活作用，这表明DEP激活Stat3需要EGFR和Src激酶激活。本研究表明，DEP诱导的氧化应激可能在激活EGFR信号传导中起关键作用，抗氧化剂预处理可防止EGFR和Stat3激活这一事实证明了这一点。这些发现表明，吸入DEP可在体外激活促炎性Stat3信号传导。
