细胞因子诱导支气管上皮细胞表达嗜酸粒细胞趋化因子

Eotaxin和新近发现的Eotaxin-2在支气管上皮细胞中的表达以及Th2型细胞因子的调节作用。以支气管上皮细胞株BEAS-2B细胞为研究对象,通过RT-PCR的方法测定Th2型细胞因子IL-4、IL-13以及促炎症因子TNF-α单独和协同刺激下BEAS-2B细胞Eotaxin和Eotaxin-2的基因表达,通过ELISA方法测定细胞培养上清液中Eotaxin蛋白的表达。EotaxinmRNA在TNF-α刺激12h后表达最高,Th2型细胞因子IL-4和IL-13与TNF-α协同刺激后表达进一步增强,Eotaxin蛋白的表达在协同刺激下也呈剂量和时间依赖性增高(P<0.01)。Eotaxin-2mRNA在TNF-α的刺激下于8h表达最高,IL-4或IL-13与TNF-α的协同刺激也使表达进一步增强,Eotaxin和Eotaxin-2两者基因表达具有相关性(P<0.05)。Th2型细胞因子可与促炎症因子TNF-α协同刺激支气管上皮细胞增强表达嗜酸粒细胞趋化因子Eotaxin和Eotaxin-2,从而吸引嗜酸粒细胞浸润至气道参与哮喘炎症过程。

Eotaxin and Eotaxin-2 expression in human bronchial epithelial cells

Eotaxin and newly identified eotaxin,2 are chemokines that play important role in the pathogenesis of allergic disease like asthma. Their expression in bronchial epithelial cell have some relationship with the Th2 cytokine regulation which are important in airway allergic inflammation. We studied the regulation role of eotaxin and eotaxin,2 expression by Th2 cytokine and analyzed their relationship in normal human bronchial epithelial cell line,BEAS,2B. Levels of eotaxin mRNA and protein expression in the bronchial epithelial cell line BEAS,2B were determined with RT,PCR and ELISA. RT,PCR was used to evaluate the eotaxin,2 expression under the regulation of Th2 cytokine,IL,4 and IL,13 as well as proinflammatory agent,TNF,α. It was found that eotaxin mRNA expression was the highest at the time point of 12 hours under the stimulation of TNF,α. While Th2 cytokine IL,4 and IL,13 have the amplification effect on the expression. Eotaxin protein was also elevated with the combination stimulation of proinflammatory agent TNF,α and IL,4 in dose and time dependent manner(P<0.01). These results were also observed when the cells were stimulated by TNF,α and IL,13. Eotaxin,2 mRNA expression was the highest at the time point of 8 hours. Its expression evaluated by semi,quantitative RT,PCR also elevated under the co,stimulation of TNF,α and IL,4 or TNF,α and IL,13, having significant correlation with eotaxin(P<0.05). This study demonstrate that Th2 cytokine like IL,4 and IL,13 enhance eotaxin and eotaxin,2 expression when co,stimulated with proinflammatory agent TNF,α. Th2 cytokines existence is the strong evidence for bronchial epithelial cells taking part in the allergic inflammation, especially in eosinophils recruitment.