title: Blocking of thromboxane A₂ receptor attenuates airway mucus hyperproduction induced by cigarette smoke.
abstract: Cigarette smoking is one of the risk factors for chronic obstructive pulmonary disease (COPD). In this study, we investigated the effects of thromboxane A2 (TxA2) receptor antagonists on airway mucus production induced by cigarette smoke. Rats were exposed to cigarette smoke 1h/day, 6 days/week for 4 weeks. Seratrodast (2, 5, 10mg/kg day) was administered intragastrically prior to smoke exposure. Thromboxane B2 (TxB2) in the bronchoalveolar lavage fluid and lung tissues was determined by enzyme immunoassay. Airway mucus production was determined by alcin-blue/periodic acid sthiff (AB-PAS) staining, Muc5ac immunohistochemical staining, and RT-PCR. The phosphorylation of ERK and p38 was evaluated by Western blotting. Seratrodast reduced the overproduction of TxB2 in both bronchoalveolar lavage fluid and lung tissues. Cigarette smoke exposure markedly increased AB/PAS-stained goblet cells and rat Muc5ac expression in the airway, which was significantly attenuated by seratrodast administration. The induced phosphorylation of ERK and p38 was also attenuated by seratrodast. TxA2 receptor antagonist could reduce Muc5ac production induced by cigarette smoke in vivo, possibly through the mitogen-activated protein kinases (MAPK) signaling pathway.
authors: Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors: Jing
authors: J
authors: An
authors: Ji-Qiong
authors: JQ
authors: Li
authors: Tao
authors: T
authors: Wang
authors: Xiao-Ou
authors: XO
authors: Li
authors: Ling-Li
authors: LL
authors: Guo
authors: Chun
authors: C
authors: Wan
authors: Zeng-Lin
authors: ZL
authors: Liao
authors: Jia-Jia
authors: JJ
authors: Dong
authors: Dan
authors: D
authors: Xu
authors: Fu-Qiang
authors: FQ
authors: Wen
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006538:Heptanoic Acids / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D055271:Mucin 5AC / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors*; D012906:Smoke / Q000009:adverse effects*; D013929:Thromboxane B2 / Q000378:metabolism; D014026:Nicotiana
chemical_list: D018927:Anti-Asthmatic Agents; D016227:Benzoquinones; D006538:Heptanoic Acids; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D012906:Smoke; C060230:seratrodast; D013929:Thromboxane B2; D020928:Mitogen-Activated Protein Kinases