Gilchrist Mark, Henderson William R, Clark April E, Simmons Randi M, Ye Xin, Smith Kelly D, Aderem Alan
Institute for Systems Biology, Seattle, WA 98103, USA.
J Exp Med. 2008 Sep 29;205(10):2349-57. doi: 10.1084/jem.20072254. Epub 2008 Sep 15.
We recently demonstrated the pivotal role of the transcription factor (TF) activating TF 3 (ATF3) in dampening inflammation. We demonstrate that ATF3 also ameliorates allergen-induced airway inflammation and hyperresponsiveness in a mouse model of human asthma. ATF3 expression was increased in the lungs of mice challenged with ovalbumin allergen, and this was associated with its recruitment to the promoters of genes encoding Th2-associated cytokines. ATF3-deficient mice developed significantly increased airway hyperresponsiveness, pulmonary eosinophilia, and enhanced chemokine and Th2 cytokine responses in lung tissue and in lung-derived CD4(+) lymphocytes. Although several TFs have been associated with enhanced inflammatory responses in the lung, ATF3 attenuates the inflammatory responses associated with allergic airway disease.
我们最近证明了转录因子（TF）激活转录因子3（ATF3）在减轻炎症中起关键作用。我们证明，在人类哮喘小鼠模型中，ATF3还能改善变应原诱导的气道炎症和高反应性。用卵清蛋白变应原攻击的小鼠肺中，ATF3表达增加，这与其募集到编码Th2相关细胞因子的基因启动子有关。ATF3缺陷小鼠的气道高反应性、肺嗜酸性粒细胞增多以及肺组织和肺源性CD4(+)淋巴细胞中的趋化因子和Th2细胞因子反应显著增强。尽管有几种转录因子与肺部炎症反应增强有关，但ATF3可减轻与过敏性气道疾病相关的炎症反应。
