Characterization of Toll-like receptors in primary lung epithelial cells: strong impact of the TLR3 ligand poly(I:C) on the regulation of Toll-like receptors, adaptor proteins and inflammatory response.
Characterization of Toll-like receptors in primary lung epithelial cells: strong impact of the TLR3 ligand poly(I:C) on the regulation of Toll-like receptors, adaptor proteins and inflammatory response.
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DOI：
10.1186/1476-9255-2-16
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发表时间：
2005-11-29
期刊：
影响因子：
--
通讯作者：
Seither P
中科院分区：
文献类型：
--
作者：
Ritter M;Mennerich D;Weith A;Seither P
细菌和病毒性急性加重在包括COPD或哮喘在内的多种肺部疾病中起着至关重要的作用。由于肺上皮细胞是影响免疫反应的各种炎症介质的主要来源，我们分析了原代肺上皮细胞对Toll样受体（TLR）识别的不同微生物分子的炎症反应。详细分析TLR配体对原代小气道上皮细胞分泌细胞因子、趋化因子和基质金属蛋白酶的影响。此外，研究了小气道上皮细胞中TLR及其衔接蛋白表达的调控。我们的数据表明，病毒dsRNA的合成类似物poly（I：C）在测试的配体中介导最强的促炎作用，包括增加IL-6、IL-8、TNF-α、GM-CSF、GRO-α、TARC、MCP-1、MIP-3α、RANTES、IFN-β、IP-10和ITAC的分泌以及增加MMP-1、MMP-8、MMP-9、MMP-10和MMP-13的释放。此外，我们的数据显示，poly（I：C）以及1型和2型细胞因子对小气道上皮细胞中TLR和TLR信号传导相关分子的表达具有显著影响。Poly（I：C）诱导TLR 1、TLR 2和TLR 3的表达升高，并增加通用TLR衔接子MyD 88和IRAK-2的基因表达。同时，poly（I：C）降低TLR 5、TLR 6和TOLLIP的表达。Poly（I：C）是病毒dsRNA和TLR 3配体的类似物，在小气道上皮细胞中引发强烈的炎症反应，这可能导致哮喘或COPD等肺部疾病的病毒加重。假设poly（I：C）对Toll样受体和TLR信号传导中涉及的分子的表达的显著作用影响肺上皮对病毒和细菌感染的免疫应答。同样，考虑到外源性和内源性TLR配体分别对Th 1或Th 2驱动的肺部炎症如COPD或哮喘的影响，1型和2型细胞因子对TLR表达的调节是重要的。
Bacterial and viral exacerbations play a crucial role in a variety of lung diseases including COPD or asthma. Since the lung epithelium is a major source of various inflammatory mediators that affect the immune response, we analyzed the inflammatory reaction of primary lung epithelial cells to different microbial molecules that are recognized by Toll-like receptors (TLR). The effects of TLR ligands on primary small airway epithelial cells were analyzed in detail with respect to cytokine, chemokine and matrix metalloproteinase secretion. In addition, the regulation of the expression of TLRs and their adaptor proteins in small airway epithelial cells was investigated. Our data demonstrate that poly(I:C), a synthetic analog of viral dsRNA, mediated the strongest proinflammatory effects among the tested ligands, including an increased secretion of IL-6, IL-8, TNF-α, GM-CSF, GRO-α, TARC, MCP-1, MIP-3α, RANTES, IFN-β, IP-10 and ITAC as well as an increased release of MMP-1, MMP-8, MMP-9, MMP-10 and MMP-13. Furthermore, our data show that poly(I:C) as well as type-1 and type-2 cytokines have a pronounced effect on the expression of TLRs and molecules involved in TLR signaling in small airway epithelial cells. Poly(I:C) induced an elevated expression of TLR1, TLR2 and TLR3 and increased the gene expression of the general TLR adaptor MyD88 and IRAK-2. Simultaneously, poly(I:C) decreased the expression of TLR5, TLR6 and TOLLIP. Poly(I:C), an analog of viral dsRNA and a TLR3 ligand, triggers a strong inflammatory response in small airway epithelial cells that is likely to contribute to viral exacerbations of pulmonary diseases like asthma or COPD. The pronounced effects of poly(I:C) on the expression of Toll-like receptors and molecules involved in TLR signaling is assumed to influence the immune response of the lung epithelium to viral and bacterial infections. Likewise, the regulation of TLR expression by type-1 and type-2 cytokines is important considering the impact of exogenous and endogenous TLR ligands on Th1 or Th2 driven pulmonary inflammations like COPD or asthma, respectively.