Particulate matter exposure promotes Pseudomonas aeruginosa invasion into airway epithelia by upregulating PAFR via the
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RESEARCH ARTICLE
Particulate matter exposure promotes Pseudomonas aeruginosa invasion into airway epithelia by upregulating PAFR via the ROS‑mediated PI3K pathway Jinguo Liu1 · Xiaoyan Chen1 · Jian Zhou1 · Ling Ye1 · Dong Yang1 · Yuanlin Song1,2,3 Received: 8 August 2019 / Accepted: 14 May 2020 © Japan Human Cell Society 2020
Abstract Over exposure to particulate matter (PM) could irritate respiratory tract infection; while, Pseudomonas aeruginosa (P. aeruginosa) is one of the main common pathogens. Our study aims are to define whether PM exposure enhances the invasion of P. aeruginosa into the airway epithelia and to characterize the underlying mechanisms. Human bronchial epithelial cells (BEAS-2B) or BEAS-2B transfected by PAFR siRNA were challenged with PM and pretreated with N-acetylcysteine (NAC), LY294002 (PI3K inhibitor), BAY 11-7082 (NF-κB inhibitor), or CV-3988 (PAFR antagonist). P. aeruginosa invasion was evaluated using colony-forming units assay and confocal microscopy. Real-time RT-PCR, immunofluorescence, flow cytometry and western blotting were used to detect the genes or proteins expression. PM exposure promoted P. aeruginosa invasion into BEAS-2B cells through ROS-mediated PI3K pathway which enhanced the expression of PAFR, which could be alleviated by treatment with NAC, LY294002, and BAY 11-7082. Furthermore, NAC and PAFR siRNA attenuated PM-stimulated activation of PI3K pathway. Treatment with PAFR antagonist and siRNA also alleviated PM exposure-induced P. aeruginosa invasion into BEAS-2B cells. Our results demonstrated that PM exposure increased the PAFR expression and activated the PI3K pathway in a ROS-dependent manner. Upregulated PAFR and activated PI3K pathway formed a positive regulatory loop and promoted the invasion of P. aeruginosa into airway epithelia. These mechanisms may provide a novel approach against P.aeruginosa invasion. Keywords Particulate matter · Oxidative stress · Pseudomonas aeruginosa · Platelet-activating factor receptor
Introduction
Jinguo Liu and Xiaoyan Chen contributed equally to this paper. * Dong Yang yang.dong@zs‑hospital.sh.cn * Yuanlin Song [email protected] 1
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University and Shanghai Respiratory Research Institute, 180 Fenglin Road, Shanghai 200032, People’s Republic of China
2
Department of Respiratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China
3
Department of Pulmonary Medicine, Zhongshan Hospital, Qingpu Branch, Shanghai, People’s Republic of China
Air pollution is a rapidly increasing serious problem in developing countries. Exposure to air particulate matter (PM) was one of the main global risk factors for almost 7 million deaths in 2012 [1]. Such exposure has been associated with an increasing risk of infections as pneumonia [2, 3]. Accumulating data demonstrated that PM exposure might weaken the function of airway epithelia and alveolar macrophages and result in higher risks of infection [4, 5] and Pseudomonas aer
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