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

Mechanisms of mucin production by rhinovirus infection in cultured human airway epithelial cells
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DOI:
10.1016/j.resp.2005.11.006
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发表时间:
2006-12-01
影响因子:
2.3
通讯作者:
Sasaki, Hidetada
Sasaki, Hidetada
中科院分区:
医学4区
文献类型:
--
作者:
Inoue, Daisuke;Yamaya, Mutsuo;Sasaki, Hidetada

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粘液分泌过多与鼻病毒(RV)感染引起的支气管哮喘和慢性阻塞性肺病(COPD)的恶化有关。我们研究了 RV 感染诱导人气管表面上皮细胞和粘膜下腺细胞产生粘蛋白的机制。 RV14上调MUC2、MUC3、MUC5AC、MUC5B和MUC6的mRNA表达,并增加表面细胞上清液和裂解物中MUC5AC和总粘蛋白浓度。核因子 kappa B 咖啡酸苯乙酯的抑制剂、选择性 p44/42 丝裂原激活蛋白激酶激酶 PD98059 和 U0126 的抑制剂以及选择性 Src 抑制剂 PP1 减弱了表面细胞中 MUC5AC mRNA 的表达以及 MUC5AC 和总粘蛋白糖蛋白的分泌和产生。在腺细胞中,RV14 还增加了 MUC2、MUC5AC、MUC5B 和 MUC7 的 mRNA 表达,并且抑制剂减弱了总粘蛋白糖蛋白的分泌。 Src 相关的 p44/42 丝裂原激活蛋白激酶途径可能与 RV 诱导的人类气道粘蛋白分泌过多有关。 (c) 2005 Elsevier B.V. 保留所有权利。
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 kappa B 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. (c) 2005 Elsevier B.V. All rights reserved.