1. Diminished stimulator of interferon genes production with cigarette smoke-exposure contributes to weakened anti-adenovirus vectors response and destruction of lung in chronic obstructive pulmonary disease model.
- Author
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Qin H, Huang G, Gao F, Huang B, Wang D, Hu X, Wang Y, Peng L, Luo D, Mo B, Hu C, Li Y, and Wang C
- Subjects
- A549 Cells, Adenoviridae drug effects, Adenoviridae Infections drug therapy, Animals, Cell Line, Cell Line, Tumor, Genetic Vectors drug effects, Humans, Immunity, Innate drug effects, Immunity, Innate genetics, Inflammation drug therapy, Inflammation genetics, Lung drug effects, Lung virology, Mice, Mice, Inbred C57BL, Pulmonary Disease, Chronic Obstructive virology, Pulmonary Emphysema drug therapy, Pulmonary Emphysema genetics, Pulmonary Emphysema virology, Signal Transduction drug effects, Signal Transduction genetics, Smoking adverse effects, Adenoviridae Infections genetics, Genetic Vectors genetics, Interferon-beta genetics, Pulmonary Disease, Chronic Obstructive genetics, Smoke adverse effects, Tobacco Products adverse effects
- Abstract
Cigarette smoke (CS) is the primary risk factor for chronic obstructive pulmonary disease (COPD) and dampens antiviral response, which increases viral infections and leads to COPD acute exacerbation (AECOPD). Adenovirus, a nonenveloped DNA virus, is linked with AECOPD, whose DNAs trigger innate immune response via interacting with pattern recognition receptors (PRRs). Stimulator of interferon genes (STING), as a cytosolic DNA sensor, participates in adenovirus-induced interferon β (IFNβ)-dependent antiviral response. STING is involved in various pulmonary diseases, but role of STING in pathogenesis of AECOPD is not well documented. In the present study, we explored relationship between STING and AECOPD induced by recombinant adenovirus vectors (rAdVs) and CS in wild type (WT) and STING-/- mice; and also characterized the inhibition of STING- IFNβ pathway in pulmonary epithelium exposed to cigarette smoke extract (CSE). We found that CS or CSE exposure alone dramatically inhibited STING expression, but not significantly effected IFNβ production. Moreover, CS or CSE-exposed significantly suppressed activation of STING-IFNβ pathway induced by rAdVs and suppressed clearance of rAdVs DNA. Inflammation, fibrosis and emphysema of lung tissues were exaggerated when treated with CS plus rAdVs, which further deteriorate in absences of STING. In A549 cells with knockdown of STING, we also observed enhancing apoptosis related to emphysema, especially CSE and adenovirus vectors in combination. Therefore, STING may play a protective role in preventing the progress of COPD., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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