secondhand smoke exposure causes bronchial hyperreactivity via transcriptionally upregulated endothelin and 5-hydroxytryptamine 2a receptors二手烟暴露引起支气管代通过转录调节内皮素和5 -羟色胺2 a受体.pdfVIP

Secondhand Smoke Exposure Causes Bronchial Hyperreactivity via Transcriptionally Upregulated Endothelin and 5-hydroxytryptamine 2A Receptors 1 1 2 1 1 Lei Cao , Yaping Zhang , Yong-Xiao Cao , Lars Edvinsson , Cang-Bao Xu * 1 Division of Experimental Vascular Research, Institute of Clinical Science in Lund, Lund University, Lund, Sweden, 2 Department of Pharmacology, Xi’an Jiaotong University College of Medicine, Xi’an, Shaanxi, People’s Republic of China Abstract Background: Cigarette smoke exposure is strongly associated with airway hyperreactivity (AHR) which is the main characteristic seen in asthma. The intracellular MAPK signaling pathways are suggested to be associated with the airway damage to the AHR. In the present study, we hypothesize that secondhand cigarette smoke (SHS) exposure upregulates the bronchial contractile receptors via activation of the Raf/ERK/MAPK pathway. Methodology/Principal Findings: Rats were exposed to SHS for 3 h daily for up to 8 weeks. The receptor agonists-induced bronchial contractile reactivity was analyzed with a sensitive myograph system. The mRNA transcription and protein translation of the target receptors and the kinases in Raf/ERK/MAPK pathway were investigated by real-time PCR, Western blotting and immunofluorescence, respectively. Compared with exposure to fresh air, SHS induced enhanced bronchial contractile responses mediated by the 5-hydroxytryptamine 2A (5-HT ) receptors as well as the endothelin type B (ET ) and 2A B type A (ETA) receptors. The response curves were shifted toward t