Author:
Zhang Wei,Zhang Yibin,Zhu Qi
Abstract
Abstract
Background
Long-term inhalation of cigarette smoke is considered to be one of the main causes of bronchial epithelioid cell damage, but its underlying mechanism has to be further clarified.
Methods
Gene expression at mRNA level and protein levels were detected by qRT-PCR and western blot analysis respectively. CCK-8, TUNEL assays, ELISA, western blot analysis and commercial kits were utilized to test cell viability, apoptosis inflammatory response and oxidative stress. The correlation between fatty acid binding protein 4 (FABP4) and the p38 mitogen-activated protein kinase (MAPK)/MAPK activated kinase 2 (MK2) signaling pathway was verified by western blot analysis and rescue assays.
Results
Cigarette smoke extract (CSE) exposure decreased viability, induced apoptosis and inflammatory response in 16HBE cells. Moreover, the expression of FABP4 in CSE-treated 16HBE cells was up-regulated in a time and dose-dependent manner. Ablation of FABP4 in 16HBE cells significantly protected against CSE-mediated cell viability decline and apoptosis. Further, FABP4 knockdown suppressed inflammatory response by down-regulating the elevated levels of cellular inflammatory factors including TNF-α, IL-1β, IL-6, Cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) in CSE-treated 16HBE cells. The oxidative stress induced by CSE in 16HBE cells was also inhibited by FABP4 silence as evidence by reduced ROS and MDA level but increased SOD activity caused by FABP4 silence. Finally, all the above effects of FABP4 silence on CSE-treated 16HBE cells were reversed by asiatic acid, an agonist of p38 mitogen-activated protein kinase (MAPK).
Conclusions
The up-regulation of FABP4 expression mediated by CSE exerted pro-inflammatory, pro-oxidative stress and pro-apoptotic effects on bronchial epithelial cells by activating the p38 MAPK/MK2 signaling pathway. Our findings help to further understand the underlying mechanism of cigarette smoke-induced bronchial inflammation.
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Clinical Biochemistry
Reference37 articles.
1. D’Angelo D, Ahluwalia IB, Pun E, Yin S, Palipudi K, Mbulo L. Current Cigarette Smoking, Access, and Purchases from Retail Outlets Among Students Aged 13–15 Years - Global Youth Tobacco Survey, 45 Countries, 2013 and 2014. MMWR Morb Mortal Wkly Rep. 2016;65:898–901.
2. Pinto E, Cruz M, Ramos P, Santos A, Almeida A. Metals transfer from tobacco to cigarette smoke: Evidences in smokers’ lung tissue. J Hazard Mater. 2017;325:31–5.
3. Paumgartten FJR, Gomes-Carneiro MR, Oliveira A. The impact of tobacco additives on cigarette smoke toxicity: a critical appraisal of tobacco industry studies. Cadernos de saude publica. 2017;33Suppl 3:e00132415.
4. Li E, Xu Z, Liu F, et al. Continual exposure to cigarette smoke extracts induces tumor-like transformation of human nontumor bronchial epithelial cells in a microfluidic chip. J Thorac Oncol. 2014;9:1091–100.
5. Heijink IH, de Bruin HG, Dennebos R, et al. Cigarette smoke-induced epithelial expression of WNT-5B: implications for COPD. Eur Respir J. 2016;48:504–15.
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献