PubAg

Main content area

Airborne fine particulate matter causes murine bronchial hyperreactivity via MAPK pathway‐mediated M3 muscarinic receptor upregulation

Author:
Wang, Rong, Xiao, Xue, Shen, Zhenxing, Cao, Lei, Cao, Yongxiao
Source:
Environmental toxicology 2017 v.32 no.2 pp. 371-381
ISSN:
1520-4081
Subject:
agonists, bronchi, carbachol, dimethyl sulfoxide, human health, immunohistochemistry, messenger RNA, mice, mitogen-activated protein kinase, muscarine receptors, particulates, protein synthesis, quantitative polymerase chain reaction, rats, risk factors
Abstract:
Regarding the human health effects, airborne fine particulate matter 2.5 (PM₂.₅) is an important environmental risk factor. However, the underlying molecular mechanisms are largely unknown. The present study examined the hypothesis that PM₂.₅ causes bronchial hyperreactivity by upregulated muscarinic receptors via the mitogen‐activated protein kinase (MAPK) pathway. The isolated rat bronchi segments were cultured with different concentration of PM₂.₅ for different time. The contractile response of the bronchi segments were recorded by a sensitive myograph. The mRNA and protein expression levels of M₃ muscarinic receptors were studied by quantitative real‐time PCR and immunohistochemistry, respectively. The muscarinic receptors agonist, carbachol induced a remarkable contractile response on fresh and DMSO cultured bronchial segments. Compared with the fresh or DMSO culture groups, 1.0 µg/mL of PM₂.₅ cultured for 24 h significantly enhanced muscarinic receptor‐mediated contractile responses in bronchi with a markedly increased maximal contraction. In addition, the expression levels of mRNA and protein for M₃ muscarinic receptors in bronchi of PM₂.₅ group were higher than that of fresh or DMSO culture groups. SB203580 (p38 inhibitor) and U0126 (MEK1/2 inhibitor) significantly inhibited the PM₂.₅‐induced enhanced contraction and increased mRNA and protein expression of muscarinic receptors. However, JNK inhibitor SP600125 had no effect on PM₂.₅‐induced muscarinic receptor upregulation and bronchial hyperreactivity. In conclusion, airborne PM₂.₅ upregulates muscarinic receptors, which causes subsequently bronchial hyperreactivity shown as enhanced contractility in bronchi. This process may be mediated by p38 and MEK1/2 MAPK pathways. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 371–381, 2017.
Agid:
5881260