表皮生长因子受体在臭氧致呼吸道炎症过程中的作用及其机制

臭氧是目前我国一种主要空气污染物。短期吸入高浓度臭氧可引起呼吸道炎症。申请人最近发现臭氧短期刺激可激活人支气管上皮细胞表皮生长因子受体（EGFR）；EGFR抑制剂可明显降低臭氧所致炎性细胞趋化因子白介素8（IL8）的表达。因此推测EGFR可能在臭氧所致呼吸道炎症过程中发挥重要作用。本研究目的旨在阐明臭氧激活EGFR的机制和EGFR在臭氧诱发呼吸道炎症中的作用。体外研究将以人支气管上皮细胞气液分界培养系统为模型，揭示氧化应激和蛋白激酶Src在臭氧诱发EGFR活化过程中的作用与EGFR调节臭氧所致的体外细胞炎性反应；体内实验则重点检测吸入臭氧小鼠呼吸道上皮细胞EGFR的磷酸化及EGFR在臭氧所致呼吸道炎症中的作用。本研究将为阐明臭氧所致呼吸道炎症机制提供重要实验依据。

Ozone is currently a major air pollutant in China. Short-term inhalation of high levels of ozone could result in airway inflammation. We have recently observed that acute exposure to ozone could activate EGF receptor (EGFR) on human bronchial epithelial cells, and pharmacological inhibition of EGFR markedly suppressed ozone-induced over-expression of chemokine IL8. Therefore, we assumed that EGFR may play a critical role in ozone-induced airway inflammation. The aims of this study are to reveal the mechanisms underlying ozone-induced EGFR activation and the regulatory effect of EGFR on ozone-induced inflammatory responses of primary human bronchial epithelial cells and airway inflammation in mice. The in vitro studies will be performed to characterize the involvement of oxidative stress and cytosolic tyrosine kinase Src in ozone-induced EGFR activation, and the regulatory effect of EGFR on ozone-induced cellular inflammatory responses. The animal study will determine the phosphorylation of EGFR in airway epithelium of mice exposed to ozone and the role of EGFR in ozone-induced airway inflammation. This study is expected to provide essential evidence for elucidation of mechanisms of ozone-induced airway inflammation.