STAT3 activation inhibits human bronchial epithelial cell apoptosis in response to cigarette smoke exposure.
We have previously reported that cigarette smoke can induce DNA damage in human lung cells without leading to apoptosis or necrosis. In this study, we report that STAT3 is required for the survival of human bronchial epithelial cells (HBECs) following cigarette smoke-induced DNA damage. Cigarette smoke extract (CSE) exposure increases STAT3 phosphorylation (Tyr 705) and DNA binding activity in HBECs. CSE also stimulates IL-6 release and mRNA expression. Anti-IL-6 neutralizing antibody partially blocks STAT3 activation and renders the cells sensitive to CSE-induced DNA damage. Suppression of STAT3 by siRNA results in severe DNA damage and cell death in response to CSE exposure. These findings suggest that STAT3 mediates HBEC survival in response to CSE-induced DNA damage, at least in part, through the IL-6/STAT3 signaling pathway.
Liu
Xiangde
X
Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5885, USA. xdliu@unmc.edu
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013638:Tars / Q000494:pharmacology*; D014028:Tobacco Smoke Pollution
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013638:Tars; D014028:Tobacco Smoke Pollution; C024746:tobacco tar