Angiogenin reduces immune inflammation via inhibition of TANK-binding kinase 1 expression in human corneal fibroblast cells.
Angiogenin reduces immune inflammation via inhibition of TANK-binding kinase 1 expression in human corneal fibroblast cells.
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DOI：
10.1155/2014/861435
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发表时间：
2014
影响因子：
4.6
通讯作者：
Kim JC
中科院分区：
文献类型：
--
作者：
Lee SH;Kim KW;Min KM;Kim KW;Chang SI;Kim JC
血管生成素（Angiogenin，ANG）是一种多功能的蛋白质，在血管生成和自身免疫性疾病中发挥重要作用。这种蛋白质参与先天免疫系统，并与几种炎性疾病有关。虽然ANG可能参与抗炎反应，但没有证据表明它具有直接的抗炎作用。在这项研究中，我们试图确定ANG是否对暴露于含有肿瘤坏死因子-α（TNF-α）的培养基中的人角膜成纤维细胞（HCF）具有抗炎作用。我们发现ANG降低了白细胞介素-1 β（IL-1β）、-6、-8和TNF-α受体（TNFR）1和2的mRNA表达。与此相反，ANG增加了IL-4和IL-10的mRNA表达。ANG可降低TNF-α处理的HCF中TANK结合激酶1（TBK 1）的蛋白水平。此外，ANG降低了IL-6和IL-8以及单核细胞趋化蛋白-（MCP-）1的表达。ANG可下调核因子-κB（NF-κB）的蛋白表达。提示ANG通过抑制TBK 1介导的NF-κB核转位抑制TNF-α诱导的HCF炎症反应。这些新的结果可能在免疫介导的炎症治疗靶点的选择中发挥重要作用，并可能揭示免疫介导的炎症性疾病的发病机制。
Angiogenin (ANG) is reportedly multifunctional, with roles in angiogenesis and autoimmune diseases. This protein is involved in the innate immune system and has been implicated in several inflammatory diseases. Although ANG may be involved in the anti-inflammatory response, there is no evidence that it has direct anti-inflammatory effects. In this study we sought to determine whether ANG has an anti-inflammatory effect in human corneal fibroblasts (HCFs) exposed to media containing tumor necrosis factor-alpha (TNF-α). We found that ANG reduced the mRNA expression of interleukin-1 beta (IL-1β), -6, -8 and TNF-α receptors (TNFR) 1 and 2. In contrast, ANG increased the mRNA expression of IL-4 and -10. Protein levels of TANK-binding kinase 1 (TBK1) were reduced by ANG in HCFs treated with TNF-α. Moreover, ANG diminished the expression of IL-6 and -8 and monocyte chemotactic protein- (MCP-) 1. The protein expression of nuclear factor-κB (NF-κB) was downregulated by ANG treatment. These findings suggest that ANG suppressed the TNF-α-induced inflammatory response in HCFs through inhibition of TBK1-mediated NF-κB nuclear translocation. These novel results are likely to play a significant role in the selection of immune-mediated inflammatory therapeutic targets and may shed light on the pathogenesis of immune-mediated inflammatory diseases.
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