Activation of Human Bronchial Epithelial Cells by Inflammatory Cytokines IL-27 and TNF-α: Implications for Immunopathophysiology of Airway Inflammation
Activation of Human Bronchial Epithelial Cells by Inflammatory Cytokines IL-27 and TNF-α: Implications for Immunopathophysiology of Airway Inflammation
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DOI：
10.1002/jcp.22094
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发表时间：
2010-06-01
影响因子：
5.6
通讯作者：
Lam, Christopher W. K.
中科院分区：
文献类型：
--
作者：
Cao, Ju;Wong, Chun K.;Lam, Christopher W. K.
白细胞介素（IL）-27是由抗原呈递细胞在免疫应答中产生的IL-6/IL-12家族细胞因子的成员。IL-27可以驱动初始T细胞定型为T辅助细胞I型（Thl）表型，并在感染的后期抑制炎症。已显示人支气管上皮细胞表达IL-27受体复合物。在这项研究中，我们研究了IL-27单独或与炎性细胞因子肿瘤坏死因子（TNF）-α联合对人原代支气管上皮细胞促炎活化的体外作用以及潜在的细胞内信号传导机制。发现IL-27增强人支气管上皮细胞表面细胞间粘附分子I（ICAM-1）的表达，并且在IL-27和TNF-α的联合处理中观察到对ICAM-1表达的协同作用。虽然IL-27没有改变支气管上皮细胞的基础IL-6分泌，但它可以显著增加TNF-α诱导的IL-6释放。这些对ICAM-1和IL-6上调的协同作用部分归因于IL-27诱导的TNF-α受体（p55 TNFR）表达的升高。进一步的研究表明，IL-27和TNF-α刺激的人支气管上皮细胞中ICAM-1和IL-6的升高受到磷脂酰肌醇3-OH激酶（PI 3 K）-Akt、p38丝裂原活化蛋白激酶和核因子-κ B通路的不同调节。因此，我们的研究结果提供了一个新的见解参与气道炎症的分子机制。J.细胞。223：788-797，2010。(C)2010 Wiley-Liss，Inc.
Interleukin (IL)-27 is a member of IL-6/IL-12 family cytokines produced by antigen-presenting cells in immune responses. IL-27 can drive the commitment of naive T cells to a T helper type I (Thl) phenotype and inhibit inflammation in later phases of infection. Human bronchial epithelial cells have been shown to express IL-27 receptor complex. In this study, we investigated the in vitro effects of IL-27, alone or in combination with inflammatory cytokine tumor necrosis factor (TNF)-alpha on the pro-inflammatory activation of human primary bronchial epithelial cells and the underlying intracellular signaling mechanisms. IL-27 was found to enhance intercellular adhesion molecule I (ICAM-I) expression on the surface of human bronchial epithelial cells, and a synergistic effect was observed in the combined treatment of IL-27 and TNF-alpha on the expression of ICAM-I. Although IL-27 did not alter the basal IL-6 secretion from bronchial epithelial cells, it could significantly augment TNF-alpha-induced IL-6 release. These synergistic effects on the up-regulation of ICAM-1 and IL-6 were partially due to the elevated expression of TNF-alpha receptor (p55TNFR) induced by IL-27. Further investigations showed that the elevation of ICAM-I and IL-6 in human bronchial epithelial cells stimulated by IL-27 and TNF-alpha was differentially regulated by phosphatidylinositol 3-OH kinase (PI3K)-Akt, p38 mitogen-activated protein kinase, and nuclear factor-kappa B pathways. Our results therefore provide a new insight into the molecular mechanisms involved in airway inflammation. J. Cell. Physiol. 223: 788-797, 2010. (C) 2010 Wiley-Liss, Inc.