Innate Inflammatory Responses of Pediatric Cystic Fibrosis Airway Epithelial Cells Effects of Nonviral and Viral Stimulation
Innate Inflammatory Responses of Pediatric Cystic Fibrosis Airway Epithelial Cells Effects of Nonviral and Viral Stimulation
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DOI：
10.1165/rcmb.2010-0368oc
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发表时间：
2011-06-01
影响因子：
6.4
通讯作者：
Stick, Stephen M.
中科院分区：
文献类型：
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作者：
Sutanto, Erika N.;Kicic, Anthony;Stick, Stephen M.
囊性纤维化(CF)的气道上皮细胞(AECs)是否具有内在的促炎作用，目前尚有争议。本研究的目的是与健康对照组相比，研究儿童CF患者AECs的炎性特征。我们从健康儿童(12例)和CF儿童(27例)获取血管内皮细胞。用干扰素-γ、脂多糖(由干扰素-γ、IL-1β、肿瘤坏死因子-α和脂多糖组成的一种鸡尾酒)或用人鼻病毒(HRV)刺激细胞，以评估生化和功能特性。用酶联免疫吸附试验检测细胞因子的产生。通过产生单链DNA来检测对HRV感染的细胞凋亡反应。我们的结果表明，在单层培养中，CFs和健康细胞具有相似的形态。与健康细胞相比，CF细胞结构性地产生更多的IL-6、IL-1β和前列腺素E-2，而IL-8和可溶性细胞间黏附分子-1的水平相似，并通过反复传代保持这一特征。用脂多糖或细胞因子刺激后，CF细胞和非CF细胞产生的IL-8水平相近。相反，暴露在HRV1b环境中的CF细胞与非CF细胞相比，IL-8的产生显著增加。与非CF细胞相比，暴露于HRV1b后，CF细胞的细胞凋亡率减少，病毒复制增加。我们的结论是，对于促炎症刺激，CF和健康的AEC具有相似的基础和刺激的IL-8表达，但在HRV感染的反应中，IL-8的释放增加。IL-8的升高，加上CF细胞对HRV的抑制的凋亡反应，可能有助于在生命早期反复发生病毒感染的情况下加剧呼吸道炎症。
There is controversy regarding whether cystic fibrosis (CF) airway epithelial cells (AECs) are intrinsically proinflammatory. The objective of the current study was to characterize the inflammatory profiles of AECs from children with CF compared with cells from healthy control subjects. We obtained AECs from healthy children (12) and children with CF (27). Biochemical and functional characteristics were assessed by stimulating cells with IFN gamma, LPS, a cocktail referred to as cytomix, which consists of IFN gamma, IL-1 beta, TNF-alpha, and LPS, or with human rhinovirus (HRV). Cytokine production was assessed using ELISA. Apoptotic responses to HRV infection were measured via production of single-stranded DNA. Our results indicated that CF and healthy cells exhibited similar morphology in monolayer culture. CF cells constitutively produced greater amounts of IL-6, IL-1 beta, and prostaglandin E-2, but similar levels of IL-8 and soluble intracellular adhesion molecule-1 compared with healthy cells, and this profile was maintained through repeated passage. Stimulation with LPS or cytomix elicited similar levels of IL-8 in CF and non-CF cells. In contrast, exposure to HRV1b resulted in a marked increase in IL-8 production from CF compared with non-CF cells. CF cells also exhibited reduced apoptosis and increased viral replication compared with non-CF cells after exposure to HRV1b. We conclude that CF and healthy AECs have similar basal and stimulated expression of IL-8 in response to proinflammatory stimuli, but elevated IL-8 release in response to HRV infection. The elevated IL-8, together with dampened apoptotic responses by CF cells to HRV, could contribute to augmented airway inflammation in the setting of recurrent viral infections early in life.