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Fine-particulate matter aggravates cigarette smoke extract–induced airway inflammation via Wnt5a–ERK pathway in COPD

Authors Wang Z, Zhao J, Wang T, Du X, Xie J

Received 23 November 2018

Accepted for publication 11 February 2019

Published 9 May 2019 Volume 2019:14 Pages 979—994


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Chunxue Bai

Zhihua Wang, Junling Zhao, Ting Wang, Xiaohui Du, Jungang Xie

Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China

Background: Exposure to environmental particulate matter (PM) ≤2.5 µm in diameter (PM2.5) and smoking are common contributors to COPD, and pertinent research implicates both factors in pulmonary inflammation. Using in vivo mouse and in vitro human cellular models, we investigated the joint impact of PM2.5 pollution, and cigarette smoke (CS) in mice or cigarette-smoke extract (CSE) in cells on COPD inflammation, and explored potential mechanisms.
Methods: Tissue changes in lungs of C57BL/6 mice exposed to PM2.5 and CS were studied by light microscopy, H&E, immunochemistry, and immunofluorescence-stained sections. Levels of inflammatory factors induced by PM2.5/CS in mice and PM2.5/CSE in 16HBE cells were also monitored by quantitative reverse-transcription (qRT)-PCR and ELISA. Expression of genes related to the Wnt5a-signaling pathway was assessed at transcriptional and protein levels using immunofluorescence, qRT-PCR, and Western blotting.
Results: Inflammatory response to combined exposure of PM2.5 and CS or CSE in mouse and 16HBE cells surpassed responses incited separately. Although separate PM2.5 and CS/CSE exposure upregulated the expression of Wnt5a (a member of the Wnt-secreted glycoprotein family), combined PM2.5 and CS/CSE exposure produced a steeper rise in Wnt5a levels. Use of a Wnt5a antagonist (BOX5) successfully blocked related inflammatory effects. ERK phosphorylation appeared to mediate the effects of Wnt5a in the COPD model, promoting PM2.5 aggravation of CS/CSE-induced airway inflammation.
Conclusion: Our findings suggest that combined PM2.5 and CS/CSE exposure induce airway inflammation and Wnt5a expression in vivo in mice and in vitro in 16HBE cells. Furthermore, PM2.5 seems to aggravate CS/CSE-induced inflammation via the Wnt5a–ERK pathway in the context of COPD.

Keywords: COPD, airway inflammation, PM2.5, Wnt5a

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