Progressive changes in inflammatory and matrix adherence of bronchial epithelial cells with persistent respiratory syncytial virus (RSV) infection (progressive changes in RSV infection).

Progressive changes in inflammatory and matrix adherence of bronchial epithelial cells with persistent respiratory syncytial virus (RSV) infection (progressive changes in RSV infection).
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DOI:
10.3390/ijms140918024
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发表时间:
2013-09-03
影响因子:
5.6
通讯作者:
Qu X
Qu X
中科院分区:
生物学2区
文献类型:
--
作者:
Liu X;Qin X;Xiang Y;Liu H;Gao G;Qin L;Liu C;Qu X

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除了呼吸道合胞病毒(RSV)的急性表现外,持续感染可能与慢性呼吸道疾病的长期并发症有关。为了了解RSV诱导的长期后果的机制,我们建立了体外RSV(A2株)感染模型,使用持续四代以上的人支气管上皮(16HBE)细胞,并分析了细胞炎症和基质黏附。感染呼吸道合胞病毒(MOI)0.0067的细胞在第二代(G2)或G3经历了溶细胞性或流产感染,但大多数存活到G4。G1期和G2期细胞形态、白细胞和基质黏附无明显变化,但随后部分由细胞间黏附分子-1(ICAM-1)介导的白细胞黏附和细胞因子/趋化因子分泌急剧增加,部分由E-钙粘附素介导的基质黏附减少,直至细胞死亡。细胞间黏附分子-1抗体可抑制感染-16HBE细胞分泌肿瘤坏死因子-α,提示肿瘤坏死因子-α分泌与细胞间黏附分子-1表达之间的正反馈可能在炎症加重过程中起重要作用。这些数据表明16HBE细胞对RSV的敏感性以及它们产生长期进行性RSV感染的能力,这可能有助于炎症动员和上皮脱落。
In addition to the acute manifestations of respiratory syncytial virus (RSV), persistent infection may be associated with long-term complications in the development of chronic respiratory diseases. To understand the mechanisms underlying RSV-induced long-term consequences, we established an in vitro RSV (strain A2) infection model using human bronchial epithelial (16HBE) cells that persists over four generations and analyzed cell inflammation and matrix adherence. Cells infected with RSV at multiplicity of infection (MOI) 0.0067 experienced cytolytic or abortive infections in the second generation (G2) or G3 but mostly survived up to G4. Cell morphology, leukocyte and matrix adherence of the cells did not change in G1 or G2, but subsequently, leukocyte adherence and cytokine/chemokine secretion, partially mediated by intercellular adhesion molecule-1 (ICAM-1), increased drastically, and matrix adherence, partially mediated by E-cadherin, decreased until the cells died. Tumor necrosis factor-α (TNF-α) secretion was inhibited by ICAM-1 antibody in infected-16HBE cells, suggesting that positive feedback between TNF-α secretion and ICAM-1 expression may be significant in exacerbated inflammation. These data demonstrate the susceptibility of 16HBE cells to RSV and their capacity to produce long-term progressive RSV infection, which may contribute to inflammation mobilization and epithelial shedding.
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