title: Airborne fine particulate matter causes murine bronchial hyperreactivity via MAPK pathway-mediated M3muscarinic receptor upregulation.
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 PM2.5causes 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 PM2.5for different time. The contractile response of the bronchi segments were recorded by a sensitive myograph. The mRNA and protein expression levels of M3muscarinic 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 PM2.5cultured 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 M3muscarinic receptors in bronchi of PM2.5group 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 PM2.5upregulates 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.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.|Department of Pharmacy, the Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Environmental Science and Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
authors.forename: Yongxiao
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009924:Organ Culture Techniques; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043587:Receptor, Muscarinic M3 / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D043587:Receptor, Muscarinic M3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: MAPK pathway; airborne fine particulate matter; bronchial hyperreactivity; muscarinic receptor