EGR-1 regulates Ho-1 expression induced by cigarette smoke.
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-1 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.
Chen
Huaqun
H
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210029, China. chenhuaqun@njnu.edu.cn
Wang
Lijuan
L
Gong
Tao
T
Yu
Yang
Y
Zhu
Chunhua
C
Li
Fen
F
Wang
Li
L
Li
Chaojun
C
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002467:Cell Nucleus / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012906:Smoke; D012907:Smoking / Q000378:metabolism* / Q000473:pathology; D014026:Nicotiana
D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D012906:Smoke; D051547:Heme Oxygenase-1