The T cell-specific CXC chemokines IP-10, Mig, and I-TAC are expressed by activated human bronchial epithelial cells.
The T cell-specific CXC chemokines IP-10, Mig, and I-TAC are expressed by activated human bronchial epithelial cells.
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DOI：
10.4049/jimmunol.162.6.3549
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发表时间：
1999-03
影响因子：
4.4
通讯作者：
Alain Sauty;Michelle Dziejman;R. Taha;Albert S. Iarossi;K. Neote;Eduardo A. Garcia-Zepeda;Qutayba A. Hamid;Andrew D. Luster
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文献类型：
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作者：
Alain Sauty;Michelle Dziejman;R. Taha;Albert S. Iarossi;K. Neote;Eduardo A. Garcia-Zepeda;Qutayba A. Hamid;Andrew D. Luster
激活的T细胞募集到粘膜表面，如气道上皮，在宿主防御和这些部位炎性疾病的发展中是重要的。因此，我们询问CXC趋化因子IFN诱导的10 kDa蛋白（IP-10）、IFN-γ诱导的单核因子（Mig）和IFN诱导的T细胞α-化学引诱物（I-TAC）（通过趋化因子受体CXCR 3的信号传导特异性化学吸引活化的T细胞）是否在呼吸道上皮细胞中可诱导。在正常人支气管上皮细胞（NHBEC）和两种人呼吸道上皮细胞系A549和BEAS-2B中研究了促炎细胞因子（包括IFN-γ（Th 1型细胞因子）、Th 2型细胞因子（IL-4、IL-10和IL-13）和地塞米松）的作用。我们发现，IFN-γ，而不是TNF-α或IL-1 β，强烈诱导IP-10，Mig和I-TAC mRNA的积累，主要在NHBEC和TNF-α和IL-1 β协同IFN-γ诱导在所有三种细胞类型。在IFN-γ/TNF-α刺激的NHBEC的上清液中检测到高水平的IP-10蛋白（> 800 ng/ml）。地塞米松和Th 2细胞因子均不调节IP-10、Mig或I-TAC表达。由于IFN-γ在结核病（TB）中上调，我们使用原位杂交研究了IP-10在TB患者气道中的表达，发现IP-10 mRNA在支气管上皮中表达。此外，与正常对照组相比，肺结核患者支气管肺泡灌洗获得的IP-10阳性细胞显著增加。这些结果表明，活化的支气管上皮是IP-10、Mig和I-TAC的重要来源，其在肺疾病如TB（其中IFN-γ高度表达）中在活化的T细胞的募集中发挥重要作用。
Recruitment of activated T cells to mucosal surfaces, such as the airway epithelium, is important in host defense and for the development of inflammatory diseases at these sites. We therefore asked whether the CXC chemokines IFN-induced protein of 10 kDa (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T-cell alpha-chemoattractant (I-TAC), which specifically chemoattract activated T cells by signaling through the chemokine receptor CXCR3, were inducible in respiratory epithelial cells. The effects of proinflammatory cytokines, including IFN-gamma (Th1-type cytokine), Th2-type cytokines (IL-4, IL-10, and IL-13), and dexamethasone were studied in normal human bronchial epithelial cells (NHBEC) and in two human respiratory epithelial cell lines, A549 and BEAS-2B. We found that IFN-gamma, but not TNF-alpha or IL-1 beta, strongly induced IP-10, Mig, and I-TAC mRNA accumulation mainly in NHBEC and that TNF-alpha and IL-1 beta synergized with IFN-gamma induction in all three cell types. High levels of IP-10 protein (> 800 ng/ml) were detected in supernatants of IFN-gamma/TNF-alpha-stimulated NHBEC. Neither dexamethasone nor Th2 cytokines modulated IP-10, Mig, or I-TAC expression. Since IFN-gamma is up-regulated in tuberculosis (TB), using in situ hybridization we studied the expression of IP-10 in the airways of TB patients and found that IP-10 mRNA was expressed in the bronchial epithelium. In addition, IP-10-positive cells obtained by bronchoalveolar lavage were significantly increased in TB patients compared with normal controls. These results show that activated bronchial epithelium is an important source of IP-10, Mig, and I-TAC, which may, in pulmonary diseases such as TB (in which IFN-gamma is highly expressed) play an important role in the recruitment of activated T cells.