Expression of eotaxin by human lung epithelial cells - Induction by cytokines and inhibition by glucocorticoids
Expression of eotaxin by human lung epithelial cells - Induction by cytokines and inhibition by glucocorticoids
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DOI：
10.1172/jci119341
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发表时间：
1997-04-01
影响因子：
15.9
通讯作者：
Luster, AD
中科院分区：
文献类型：
--
作者：
Lilly, CM;Nakamura, H;Luster, AD
Eotaxin是一种有效的特异性嗜酸性粒细胞化学引诱剂，在过敏刺激后在呼吸道上皮中被动员。已知致敏动物在接触过敏原后肺中eotaxin mRNA水平升高。在本研究中，我们发现TNF α和IL-1 β诱导肺上皮细胞系A549和BEAS 2B中eotaxin mRNA的积累呈剂量依赖性，细胞因子诱导的A549细胞mRNA积累在4 h时最大，当细胞与IFN γ共刺激时显著增强。TNF α -和IL-1 β诱导的eotaxin mRNA的增加在糖皮质激素地塞米松的作用下呈剂量依赖性减弱，而在蛋白质合成抑制剂环己亚胺的作用下增强。细胞因子诱导的eotaxin mRNA表达增加与eotaxin蛋白产生和分泌增加相关，地塞米松抑制细胞因子诱导的eotaxin mRNA增加与eotaxin蛋白分泌减少相关。这些发现，连同已知的哮喘气道中TNF α和IL-1 β动员的动力学以及eotaxin的强效嗜酸性粒细胞趋化作用，确定了炎症细胞因子动员与嗜酸性粒细胞募集的联系机制，这可能与哮喘的发病机制有关。
Eotaxin is a potent and specific eosinophil chemoattractant that is mobilized in the respiratory epithelium after allergic stimulation. Pulmonary levels of eotaxin mRNA are known to increase after allergen exposure in sensitized animals. Pn this study we demonstrate that TNF alpha and IL-1 beta induce the accumulation of eotaxin mRNA in the pulmonary epithelial cell lines A549 and BEAS 2B in a dose-dependent manner, Cytokine-induced A549 cell mRNA accumulation was maximal at 4 h and was significantly enhanced when the cells were costimulated with IFN gamma. TNF alpha- and IL-1 beta-induced increases in eotaxin mRNA were diminished in a dose-dependent manner by the glucocorticoid dexamethasone and were augmented by the protein synthesis inhibitor cycloheximide. Cytokine-induced increases in eotaxin mRNA expression correlated with increased eotaxin protein production and secretion, and dexamethasone inhibition of cytokine-induced eotaxin mRNA augmentation was associated with diminished eotaxin protein secretion. These findings, together with the known kinetics of TNF alpha and IL-1 beta mobilization in asthmatic airways and the potent eosinophil chemotactic effects of eotaxin, define a mechanism linking inflammatory cytokine mobilization to eosinophil recruitment that may be relevant to the pathogenesis of asthma.