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Particulate matter exposure promotes Pseudomonas aeruginosa invasion into airway epithelia by upregulating PAFR via the ROS-mediated PI3K pathway

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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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (30772019, 81570028, 81100048), the Scientific Research Foundation for the Returned Overseas Chinese Scholars by State Education Ministry of China, Natural Science Foundation of Shanghai (16ZR1405700), the State Key Development Program of Basic Research of China (973 project) (Grant No: 2015CB553404), Shanghai Municipal Commission of Health and Family Planning (201540078).

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  1. Jinguo Liu and Xiaoyan Chen contributed equally to this paper.

Authors and Affiliations

  1. Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University and Shanghai Respiratory Research Institute, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China

    Jinguo Liu, Xiaoyan Chen, Jian Zhou, Ling Ye, Dong Yang & Yuanlin Song

  2. Department of Respiratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China

    Yuanlin Song

  3. Department of Pulmonary Medicine, Zhongshan Hospital, Qingpu Branch, Shanghai, People’s Republic of China

    Yuanlin Song

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  1. Jinguo Liu
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Correspondence to Dong Yang or Yuanlin Song.

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Liu, J., Chen, X., Zhou, J. et al. Particulate matter exposure promotes Pseudomonas aeruginosa invasion into airway epithelia by upregulating PAFR via the ROS-mediated PI3K pathway. Human Cell 33, 963–973 (2020). https://doi.org/10.1007/s13577-020-00378-y

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