EGR-1 regulates Ho-1 expression induced by cigarette smoke

被引:25
作者
Chen, Huaqun [1 ]
Wang, Lijuan [1 ]
Gong, Tao [1 ]
Yu, Yang [1 ]
Zhu, Chunhua [1 ]
Li, Fen [1 ]
Wang, Li [1 ]
Li, Chaojun [1 ,2 ,3 ]
机构
[1] Nanjing Normal Univ, Jiangsu Key Lab Mol & Med Biotechnol, Coll Life Sci, Nanjing 210029, Peoples R China
[2] Nanjing Univ, Model Anim Res Ctr, Nanjing 210095, Peoples R China
[3] Nanjing Univ, Sch Med, Nanjing 210095, Peoples R China
关键词
HO-1; EGR-1; Cigarette smoke; HEME OXYGENASE-1 GENE; OBSTRUCTIVE PULMONARY-DISEASE; HUMAN LUNG FIBROBLASTS; ACTIVATION; CELLS; LIPOPOLYSACCHARIDE; TRANSCRIPTION; PATHOGENESIS; INDUCTION; EXPOSURE;
D O I
10.1016/j.bbrc.2010.04.102
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
As an anti-oxidant molecule, heme oxygenase-1 (HO-1) has been implicated in the protection of lung injury by cigarette smoke (CS). The mechanisms regulating its expression have not been defined. In this report, the role of early growth response 1 (EGR-1) in the regulation of HO-1 expression was investigated. In C57BL/6 mice with CS exposure, HO-I was greatly increased in bronchial epithelial cells and alveolar inflammatory cells. In primary cultured mouse lung fibroblasts and RAW264.7 cells exposed to cigarette smoke water extract (CSE), an increase in HO-1 protein level was detected. In addition, CSE induced HO-1 expression was decreased in Egr-1 deficient mouse embryo fibroblasts (Egr-1(-/-) MEFs). Nuclear localization of EGR-1 was examined in mouse lung fibroblasts after exposure to CSE. Luciferase reporter activity assays showed that the enhancer region of the Ho-1 gene containing a proposed EGR-1 binding site was responsible for the induction of HO-1. A higher increase of alveolar mean linear intercept (Lm) was observed in lung tissues, and a larger increase in the number of total cells and monocytes/macrophages from bronchial alveolar lavage fluid was found in CS-exposed mice by loss of function of EGR-1 treatment. In summary, the present data demonstrate that EGR-1 plays a critical role in HO-1 production induced by CS. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:388 / 393
页数:6
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