Yan Fugui, Wu Yinfang, Liu Huiwen, Wu Yanping, Shen Huahao, Li Wen
Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Institute of Respiratory Diseases, Hangzhou, Zhejiang 310009, China.
Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Institute of Respiratory Diseases, Hangzhou, Zhejiang 310009, China.
Toxicol Lett. 2018 May 1;287:113-121. doi: 10.1016/j.toxlet.2018.01.022. Epub 2018 Jan 31.
Airborne particulate matter (PM) has been reported to be associated with a wide range of respiratory disorders. However, the mechanisms underlying PM-induced airway inflammation remain largely unknown. Generally, ATF3 negatively regulates pro-inflammatory cytokines production in response to TLR4 signaling. Here we first showed ATF3 has promoting effects in PM-induced airway inflammation in vitro an in vivo. We demonstrated PM significantly upregulated ATF3 expression in HBE cells and in mouse lung tissues. ATF3 siRNA markedly inhibited, while ATF3-recombinant over-expression plasmid significantly increased PM-induced IL-6 expression in cultured HBE cells, and PM-induced IL-6, CXCL2 expression as well as neutrophil infiltration, mucus over-production in the lung of ATF3 mice were all notably reduced relative to the wild-type littermates. Furthermore, we showed ATF3 mediated PM-induced inflammatory cytokines expression partly through NF-κB and AP-1 pathways. Our data further elucidates the mechanisms underlying PM-induced airway inflammation, and indicates ATF3 may function as different role in response to different stimuli.
据报道，空气中的颗粒物（PM）与多种呼吸系统疾病有关。然而，PM诱导气道炎症的潜在机制在很大程度上仍不清楚。一般来说，ATF3会对TLR4信号作出反应，负向调节促炎细胞因子的产生。在此，我们首次表明ATF3在体外和体内对PM诱导的气道炎症具有促进作用。我们证明，PM可显著上调HBE细胞和小鼠肺组织中ATF3的表达。ATF3 siRNA可显著抑制培养的HBE细胞中PM诱导的IL-6表达，而ATF3重组过表达质粒则显著增加该表达；相对于野生型同窝小鼠，ATF3小鼠肺中PM诱导的IL-6、CXCL2表达以及中性粒细胞浸润、黏液过度产生均显著减少。此外，我们发现ATF3部分通过NF-κB和AP-1途径介导PM诱导的炎性细胞因子表达。我们的数据进一步阐明了PM诱导气道炎症的机制，并表明ATF3在应对不同刺激时可能发挥不同作用。
