1. PM 10 exposure induces bronchial hyperresponsiveness by upreguating acetylcholine muscarinic 3 receptor.
- Author
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Xiao X, Lei Y, Yao T, Huang T, Yan P, Cao L, and Cao Y
- Subjects
- Animals, Male, Rats, Up-Regulation drug effects, Bronchi drug effects, Bronchi metabolism, Bronchi pathology, Rats, Sprague-Dawley, MAP Kinase Signaling System drug effects, Muscle, Smooth drug effects, Muscle, Smooth metabolism, Bronchoconstriction drug effects, Cytokines metabolism, Cytokines genetics, Butadienes, Nitriles, Bronchial Hyperreactivity chemically induced, Bronchial Hyperreactivity physiopathology, Bronchial Hyperreactivity metabolism, Particulate Matter toxicity, Receptor, Muscarinic M3 metabolism, Receptor, Muscarinic M3 genetics
- Abstract
Exposure to particulate matter (PM
10 ) can induce respiratory diseases that are closely related to bronchial hyperresponsiveness. However, the involved mechanism remains to be fully elucidated. This study aimed to demonstrate the effects of PM10 on the acetylcholine muscarinic 3 receptor (CHRM3) expression and the role of the ERK1/2 pathway in rat bronchial smooth muscle. A whole-body PM10 exposure system was used to stimulate bronchial hyperresponsiveness in rats for 2 and 4 months, accompanied by MEK1/2 inhibitor U0126 injection. The whole-body plethysmography system and myography were used to detect the pulmonary and bronchoconstrictor function, respectively. The mRNA and protein levels were determined by Western blotting, qPCR, and immunofluorescence. Enzyme-linked immunosorbent assay was used to detect the inflammatory cytokines. Compared with the filtered air group, 4 months of PM10 exposure significantly increased CHRM3-mediated pulmonary function and bronchial constriction, elevated CHRM3 mRNA and protein expression levels on bronchial smooth muscle, then induced bronchial hyperreactivity. Additionally, 4 months of PM10 exposure caused an increase in ERK1/2 phosphorylation and increased the secretion of inflammatory factors in bronchoalveolar lavage fluid. Treatment with the MEK1/2 inhibitor, U0126 inhibited the PM10 exposure-induced phosphorylation of the ERK1/2 pathway, thereby reducing the PM10 exposure-induced upregulation of CHRM3 in bronchial smooth muscle and CHRM3-mediated bronchoconstriction. U0126 could rescue PM10 exposure-induced pathological changes in the bronchus. In conclusion, PM10 exposure can induce bronchial hyperresponsiveness in rats by upregulating CHRM3, and the ERK1/2 pathway may be involved in this process. These findings could reveal a potential therapeutic target for air pollution induced respiratory diseases., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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