Chemokine production by the BEAS-2B human bronchial epithelial cells:: Differential regulation of eotaxin, IL-8, and RANTES by TH2-and TH1-derived cytokines
Chemokine production by the BEAS-2B human bronchial epithelial cells:: Differential regulation of eotaxin, IL-8, and RANTES by TH2-and TH1-derived cytokines
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DOI：
10.1016/s0091-6749(00)90187-8
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发表时间：
2000-01-01
影响因子：
14.2
通讯作者：
Hirai, K
中科院分区：
文献类型：
--
作者：
Fujisawa, T;Kato, Y;Hirai, K
背景：支气管上皮细胞产生多种类型的趋化因子，并可能通过募集炎性细胞而导致肺部炎症。CC趋化因子嗜酸性粒细胞趋化因子是一种有效的嗜酸性粒细胞特异性化学引诱物，已在哮喘患者的支气管上皮中检测到。目的：本研究的目的是探讨支气管哮喘中炎性细胞因子，特别是T（H）2和T（H）1衍生的细胞因子对支气管上皮细胞趋化因子产生的调节机制。将BEAS-2B人支气管上皮细胞与TNF-α、IL-4、IL-13和IFN-γ单独或组合培养，之后测定上清液中的嗜酸性粒细胞趋化因子、IL-8、用ELISA法检测RANTES蛋白。结果：TNF-α以浓度依赖性方式诱导Eotaxin、IL-8和RANTES的产生，IL-4和IL-13协同增强TNF-α诱导的Eotaxin的产生，而TNF-α诱导的IL-8的产生被茶源性细胞因子显著下调。IFN-γ，一种T（H）1细胞因子，抵消了IL-4和IL-13对嗜酸性粒细胞趋化因子产生的增强作用。TNF-α产生的RANTES不受IL-4和IL-13的影响，但IFN-γ显著增强。结论：这些结果表明，T（H）2细胞因子参与嗜酸性粒细胞在支气管哮喘中的优先招募，通过增强嗜酸性粒细胞趋化因子和减少IL-8的产生，从支气管上皮细胞和T（H）1细胞因子抵消T（H）2细胞因子的影响，通过减少嗜酸性粒细胞趋化因子的生产。
Background: Bronchial epithelial cells produce many types of chemokines and may contribute to lung inflammation by recruiting inflammatory cells. The CC chemokine eotaxin is a potent, eosinophil-specific chemoattractant that has been detected in the bronchial epithelium of patients with asthma. Objectives: The aim of this study was to investigate the regulatory mechanisms of chemokine production from bronchial epithelium by inflammatory cytokines, especially T(H)2- and T(H)1-derived cytokines, in bronchial asthma.Methods: BEAS-2B human bronchial epithelial cells were cultured with TNF-alpha, IL-4, IL-13, and IFN-gamma alone or in combination, after which supernatants were assayed for eotaxin, IL-8, and RANTES proteins with ELISA. Reverse transcription-PCR was also performed.Results: TNF-alpha induced production of eotaxin, IL-8, and RANTES in a concentration-dependent manner Both IL-4 and IL-13 synergistically enhanced TNF-alpha-induced eotaxin production, whereas IL-8 plarluction induced by TNF-alpha was significantly down-regulated by the Tea-derived cytokines. IFN-gamma, a T(H)1 cytokine, counteracted the enhancing effects of IL-4 and IL-13 on eotaxin production. RANTES production by TNF-alpha was not affected by IL-4 and IL-13 but was markedly enhanced by IFN-gamma.Conclusions:These results suggest that T(H)2 cytokines are involved in preferential recruitment of eosinophils in bronchial asthma by enhancing eotaxin and reducing IL-8 production from bronchial epithelial cells and that T(H)1 cytokines counteract the effects of T(H)2 cytokines by reducing eotaxin production.