PM2.5 activated NLRP3 inflammasome and IL-1β release in MH-S cells by facilitating autophagy via activating Wnt5a

Author:

Yuan Guanli1,Liu Yinfeng2,Wang Zheng1,Wang Xiaotong1,Han Zhuoxiao2,Yan Xixin1,Meng Aihong1ORCID

Affiliation:

1. Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China

2. Department of Breast Surgery, The First Hospital of Qinhuangdao, Qinhuangdao, China

Abstract

Particulate matter 2.5 (PM2.5)-induced pulmonary inflammation is an important issue worldwide. NLRP3 inflammasome activation has been found to be involved in pulmonary inflammation development. However, whether PM2.5 induces pulmonary inflammation by activating the NLRP3 inflammasome has not yet been fully elucidated. This study researched whether PM2.5 induces the NLRP3 inflammasomes activation to trigger pulmonary inflammation. Mice and MH-S cells were exposed to PM2.5, BOX5, and Rapamycin. Hematoxylin and eosin staining was performed on the lung tissues of mice. M1 macrophage marker CD80 expression in the lung tissues of mice and LC3B expression in MH-S cells was detected by immunofluorescence. IL-1β level in the lavage fluid and MH-S cells were detected by enzyme-linked immunosorbent assay. Protein expression was detected by Western blot. Autophagy assay in MH-S cells was performed by LC3B-GFP punctae experiment.PM2.5 exposure induced the lung injury of mice and increased NLRP3, P62, Wnt5a, LC3BII/I, and CD80 expression and IL-1β release in the lung tissues. PM2.5 treatment increased NLRP3, pro-caspase-1, cleaved caspase-1, Pro-IL-1β, Pro-IL-18, P62, LC3BII/I, and Wnt5a expression, IL-1β release, and LC3B-GFP punctae in MH-S cells. However, BOX5 treatment counteracted this effect of PM2.5 on lung tissues of mice and MH-S cells. Rapamycin reversed the effect of BOX5 on PM2.5-induced lung tissues of mice and MH-S cells.PM2.5 activated the NLRP3 inflammasome and IL-1β release in MH-S cells by facilitating the autophagy via activating Wnt5a. The findings of this study provided a new clue for the treatment of pulmonary inflammation caused by PM2.5.

Funder

Projects Funded by Hebei Provincial Finance Department in 2020

S&T Program of Hebei

Natural Science Foundation of Hebei Province

Publisher

SAGE Publications

Subject

Pharmacology,Immunology,Immunology and Allergy,Pharmacology,Immunology,Immunology and Allergy

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