Bafilomycin A1 inhibits rhinovirus infection in human airway epithelium:: effects on endosome and ICAM-1

Bafilomycin A1 inhibits rhinovirus infection in human airway epithelium:: effects on endosome and ICAM-1
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DOI:
10.1152/ajplung.2001.280.6.l1115
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发表时间:
2001-06-01
影响因子:
4.9
通讯作者:
Sasaki, H
Sasaki, H
中科院分区:
医学2区
文献类型:
--
作者:
Suzuki, T;Yamaya, M;Sasaki, H

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为了研究空泡H+- atp酶阻滞剂巴菲霉素A(1)对呼吸道上皮内鼻病毒(RV)感染的影响,我们将人气管上皮细胞原代培养物感染RV14。病毒感染证实,感染细胞中的病毒RNA和感染细胞上清液中的病毒滴度随时间增加而增加。RV14感染上调上皮细胞细胞因子和细胞间粘附分子(ICAM)-1 mRNA的表达。巴菲霉素A(1)降低RV14的病毒滴度,抑制RV14感染前后细胞因子和ICAM-1的产生。巴菲霉素A(1)降低了上皮细胞对RV14感染的易感性。RV14增加了细胞中活化的核因子- kappab,而巴菲霉素A(1)降低了活化的核因子- kappab。巴菲霉素A(1)减少上皮细胞酸性内体的数量。这些结果表明,巴菲霉素A(1)可能不仅通过阻断RV RNA进入内体,而且通过降低上皮细胞中ICAM-1的表达来抑制RV14感染。因此,巴菲霉素A(1)可能调节RV感染后的气道炎症。
To examine the effects of bafilomycin A(1), a blocker of vacuolar H+-ATPase, on rhinovirus (RV) infection in the airway epithelium, primary cultures of human tracheal epithelial cells were infected with RV14. Viral infection was confirmed by showing that viral RNA in the infected cells and the viral titers in the supernatants of infected cells increased with time. RV14 infection upregulated the production of cytokines and mRNA of intercellular adhesion molecule (ICAM)-1 in epithelial cells. Bafilomycin A(1) reduced the viral titers of RV14 and inhibited the production of cytokines and ICAM-1 before and after RV14 infection. Bafilomycin A(1) reduced susceptibility of epithelial cells to RV14 infection. RV14 increased activated nuclear factor-kappaB in the cells, and bafilomycin A(1) reduced the activated nuclear factor-kappaB. Bafilomycin A(1) decreased the number of acidic endosomes in the epithelial cells. These results suggest that bafilomycin A(1) may inhibit infection by RV14 by not only blocking RV RNA entry into the endosomes but also reducing ICAM-1 expression in the epithelial cells. Bafilomycin A(1) may therefore modulate airway inflammation after RV infection.