IL-27 enhances innate immunity of human pulmonary fibroblasts and epithelial cells through upregulation of TLR4 expression
IL-27 enhances innate immunity of human pulmonary fibroblasts and epithelial cells through upregulation of TLR4 expression
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IL-27 通过上调 TLR4 表达来增强人肺成纤维细胞和上皮细胞的先天免疫。
DOI：
10.1152/ajplung.00307.2015
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发表时间：
2016-01-15
影响因子：
4.9
通讯作者：
Cao, Ju
中科院分区：
文献类型：
--
作者：
Su, Yufeng;Yao, Hua;Cao, Ju
肺组织细胞通过释放多种细胞因子和趋化因子在肺部炎症性疾病的发病机制中发挥积极作用。然而，肺部感染期间肺组织细胞如何对微生物刺激做出反应仍不清楚。在这项研究中，我们发现社区获得性肺炎患者的支气管肺泡灌洗液和血清中IL-27水平升高。随后我们研究了 IL-27 激活原代人肺成纤维细胞和支气管上皮细胞的免疫病理学机制。我们证明，IL-27 启动通过上调 Toll 样受体 4 (TLR4) 的表达，增强了 LPS 诱导的肺成纤维细胞和支气管上皮细胞产生 IL-6 和 IL-8。 IL-27通过激活Janus激活激酶（JAK）和Jun NH2末端激酶（JNK）信号通路上调肺成纤维细胞中TLR4的表达，抑制JAK通路可以部分降低IL-27诱导的TLR4表达，而抑制JNK通路可以完全抑制IL-27诱导的TLR4表达。我们的数据表明，IL-27 在肺部感染期间通过上调 TLR4 表达来调节肺组织细胞的先天免疫。
Lung tissue cells play an active role in the pathogenesis of pulmonary inflammatory diseases by releasing a variety of cytokines and chemokines. However, how lung tissue cells respond to microbial stimuli during pulmonary infections remains unclear. In this study, we found that patients with community-acquired pneumonia displayed increased IL-27 levels in bronchoalveolar lavage fluid and serum. We subsequently examined the immunopathological mechanisms for the activation of primary human lung fibroblasts and bronchial epithelial cells by IL-27. We demonstrated that IL-27 priming enhanced LPS-induced production of IL-6 and IL-8 from lung fibroblasts and bronchial epithelia cells via upregulating Toll-like receptor-4 (TLR4) expression. IL-27 upregulated TLR4 expression in lung fibroblasts through activation of Janus-activated kinase (JAK) and Jun NH2-terminal kinase (JNK) signaling pathways, and inhibition of the JAK pathway could partially decrease IL-27-induced TLR4 expression, while inhibition of JNK pathway could completely suppress IL-27-induced TLR4 expression. Our data suggest that IL-27 modulates innate immunity of lung tissue cells through upregulating TLR4 expression during pulmonary infections.