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人呼吸道上皮细胞培养物中鼻病毒感染导致黏蛋白产生的机制

Mechanisms of mucin production by rhinovirus infection in cultured human airway epithelial cells.

作者信息

Inoue Daisuke, Yamaya Mutsuo, Kubo Hiroshi, Sasaki Takahiko, Hosoda Masayoshi, Numasaki Muneo, Tomioka Yoshihisa, Yasuda Hiroyasu, Sekizawa Kiyohisa, Nishimura Hidekazu, Sasaki Hidetada

机构信息

Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.

出版信息

Respir Physiol Neurobiol. 2006 Dec;154(3):484-99. doi: 10.1016/j.resp.2005.11.006. Epub 2005 Dec 27.

Abstract

Mucus hypersecretion relates to exacerbations of bronchial asthma and chronic obstructive pulmonary disease (COPD) caused by rhinovirus (RV) infection. We examined the mechanisms of RV infection-induced mucin production in human tracheal surface epithelial cells and submucosal gland cells. RV14 up-regulated the mRNA expression of MUC2, MUC3, MUC5AC, MUC5B and MUC6, and increased MUC5AC and total mucin concentration in supernatants and lysates of the surface cells. An inhibitor of the nuclear factor kappaB caffeic acid phenylethyl ester, inhibitors of selective p44/42 mitogen-activated protein kinase-kinase PD98059 and U0126, and a selective Src inhibitor PP1 attenuated MUC5AC mRNA expression, and secretion and production of MUC5AC and total mucin glycoprotein in the surface cells. In the gland cells, RV14 also increased mRNA expression of MUC2, MUC5AC, MUC5B and MUC7, and the inhibitors attenuated the secretion of total mucin glycoprotein. Src-related p44/42 mitogen-activated protein kinase pathway may be associated with RV-induced mucin hypersecretion in human airways.

摘要

黏液高分泌与鼻病毒(RV)感染引起的支气管哮喘和慢性阻塞性肺疾病(COPD)急性加重有关。我们研究了RV感染诱导人气管表面上皮细胞和黏膜下腺细胞黏蛋白产生的机制。RV14上调了MUC2、MUC3、MUC5AC、MUC5B和MUC6的mRNA表达,并增加了表面细胞上清液和裂解物中MUC5AC和总黏蛋白浓度。核因子κB抑制剂咖啡酸苯乙酯、选择性p44/42丝裂原活化蛋白激酶激酶抑制剂PD98059和U0126以及选择性Src抑制剂PP1可减弱表面细胞中MUC5AC mRNA表达以及MUC5AC和总黏蛋白糖蛋白的分泌与产生。在腺细胞中,RV14也增加了MUC2、MUC�AC、MUC5B和MUC7的mRNA表达,且这些抑制剂减弱了总黏蛋白糖蛋白的分泌。Src相关的p44/42丝裂原活化蛋白激酶途径可能与人气道中RV诱导的黏蛋白高分泌有关。

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