title: Cigarette smoke extract induces placental growth factor release from human bronchial epithelial cells via ROS/MAPK (ERK-1/2)/Egr-1 axis.
abstract: Etiological evidence demonstrates that there is a significant association between cigarette smoking and chronic airway inflammatory disease. Abnormal expression of placental growth factor (PlGF) has been reported in COPD, and its downstream signaling molecules have been reported to contribute to the pathogenesis of airway epithelial cell apoptosis and emphysema. However, the signaling mechanisms underlying cigarette smoke extract (CSE)-induced PlGF expression in airway microenvironment remain unclear. Herein, we investigated the effects of reactive oxygen species (ROS)-dependent activation of the mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase1/2 [ERK-1/2])/early growth response-1 (Egr-1) pathway on CSE-induced PlGF upregulation in human bronchial epithelium (HBE). The data obtained with quantitative reverse transcription polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining analyses showed that CSE-induced Egr-1 activation was mainly mediated through production of ROS and activation of the MAPK (ERK-1/2) cascade. The binding of Egr-1 to the PlGF promoter was corroborated by an ELISA-based DNA binding activity assay. These results demonstrate that ROS activation of the MAPK (ERK-1/2)/Egr-1 pathway is a main player in the regulatory mechanism for CSE-induced PlGF production and that the use of an antioxidant could partly abolish these effects. Understanding the mechanisms of PlGF upregulation by CSE in the airway microenvironment may provide rational therapeutic interventions for cigarette smoking-related airway inflammatory diseases.
authors.affiliation: Department of Respiratory, Institute of Respiratory Diseases.
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Respiratory, Institute of Respiratory Diseases.
authors.forename: Yalian
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Zhixiu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Respiratory, Institute of Respiratory Diseases.
authors.forename: Tianwen
authors.initials: T
authors.lastname: Lai
authors.affiliation: Department of Respiratory, Institute of Respiratory Diseases.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Respiratory, Institute of Respiratory Diseases.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Respiratory, Institute of Respiratory Diseases.
authors.forename: Quanchao
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Respiratory, Institute of Respiratory Diseases.
authors.forename: Binfan
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Respiratory, Institute of Respiratory Diseases.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Respiratory, Institute of Respiratory Diseases.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001665:Binding Sites; D001980:Bronchi / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D000072483:Placenta Growth Factor / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D014162:Transfection
chemical_list: D000975:Antioxidants; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C000608036:PGF protein, human; D017382:Reactive Oxygen Species; D012906:Smoke; D000072483:Placenta Growth Factor; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: airway epithelium; cigarette smoke; early growth response-1; extracellular signal-regulated kinase1/2; placental growth factor; reactive oxygen species