title: Airborne fine particulate matter induces an upregulation of endothelin receptors on rat bronchi.
abstract: Airborne fine particulate matter (PM2.5) is a risk factor for respiratory diseases. However, little is known about the effects of PM2.5 on bronchi. The present study investigated the effect of airborne PM2.5 on rat bronchi and the underlying mechanisms. Isolated rat bronchial segments were cultured for 24 h. Endothelin (ET) receptor-mediated contractile responses were recorded using a wire myograph. The mRNA and protein expression levels of ET receptors were studied using quantitative real-time PCR, Western blotting, and immunohistochemistry. The results demonstrated that ETA and ETB receptor agonists induced remarkable contractile responses on fresh and cultured bronchial segments. PM2.5 (1.0 or 3.0 μg/ml) significantly enhanced ETA and ETB receptor-mediated contractile responses in bronchi with a markedly increased maximal contraction compared to the DMSO or fresh groups. PM2.5 increased the mRNA and protein expression levels of ETA and ETB receptors. U0126 (a MEK1/2 inhibitor) and SB203580 (a p38 inhibitor) significantly suppressed PM2.5-induced increases in ETB receptor-mediated contractile responses, mRNA and protein levels. SP600125 (a JNK inhibitor) and SB203580 significantly abrogated the PM2.5-induced enhancement of ETA receptor-mediated contraction and receptor expression. In conclusion, PM2.5 upregulates ET receptors in bronchi. ETB receptor upregulation is associated with MEK1/2 and p38 pathways, and the upregulation of ETA receptor is involved in JNK and p38 pathways.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China. Electronic address: leicao@mail.xjtu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Environmental Science and Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Zhen-xing
authors.initials: ZX
authors.lastname: Shen
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China. Electronic address: yxy@xjtu.edu.cn.
authors.forename: Yong-xiao
authors.initials: YX
authors.lastname: Cao
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D052638:Particulate Matter / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000235:genetics* / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000235:genetics* / Q000378:metabolism; D012140:Respiratory Tract Diseases / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D052638:Particulate Matter; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B
keywords: Airborne fine particulate matter; Bronchial hyperreactivity; Endothelin receptor; MAPK pathway