PM2.5 Induces the Expression of Inflammatory Cytokines Via the Wnt5a/Ror2 Pathway in Human Bronchial Epithelial Cells

Overview

Journal Int J Chron Obstruct Pulmon Dis

Publisher Dove Medical Press

Specialty Pulmonary Medicine

Date 2020 Oct 30

PMID 33122903

Citations 22

Authors

Weifeng Zou

Xiaoqian Wang

Wei Hong

Fang He

Jinxing Hu

Qing Sheng

Tao Zhu

Pixin Ran

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Recently, fine particulate matter (PM2.5) was identified as the main exposure risk for COPD, and inflammation is central to the development of COPD. In this study, we investigated whether PM2.5 can induce the secretion of interleukin-6 (IL-6), IL-8 and IL-1β in human bronchial epithelial cells (HBECs) in vitro via the wingless-related integration site 5A (Wnt5a)/receptor tyrosine kinase-like orphan receptor 2 (Ror2) signaling.

Methods: The expression of Wnt5a and Ror2 was assessed by immunohistochemistry in motor vehicle exhaust (MVE)-induced Sprague-Dawley rats. HBECs were transfected with small interfering RNA (siRNA) targeting Wnt5a or Ror2 and subsequently stimulated with PM2.5.The secretion of IL-6, IL-8 and IL-1β was assessed by ELISAs, and the expression of Wnt5a/Ror2 signaling were assessed by RT-PCR and Western blotting.

Results: Both Wnt5a and Ror2 protein were increased in the lung of MVE-induced rats. HBECs exposed to PM2.5 for 24 h significantly upregulated Wnt5a and Ror2 expression and subsequently promoted the nuclear translocation of NF-κB, which increased the production of IL-1β, IL-6 and IL-8. Wnt5a siRNA prevented these outcomes. Wnt5a antagonist (BOX5) also prevented inflammatory effects. Furthermore, Ror2 siRNA blocked the NF-κB activity and inhibited the release of IL-6, IL-8 and IL-1β from PM2.5-exposed HBECs.

Conclusion: PM2.5 induces the secretion of IL-6, IL-8 and IL-1β in HBECs via the Wnt5a/Ror2 signaling, demonstrating a novel mechanism for PM2.5-associated airway inflammation.

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