Negative Effects of SIGIRR on TRAF6 Ubiquitination in Acute Lung Injury In Vitro.

Negative Effects of SIGIRR on TRAF6 Ubiquitination in Acute Lung Injury In Vitro.
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SIGIRR 对急性肺损伤体外 TRAF6 泛素化的负面影响

DOI:
10.1155/2020/5097920
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发表时间:
2020
影响因子:
4.1
通讯作者:
Jiang T
Jiang T
中科院分区:
医学3区
文献类型:
--
作者:
Tian F;Lu Q;Lei J;Ni Y;Xie N;Zhong D;Yang G;Si S;Jiang T

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在这项研究中,单个免疫球蛋白IL-1受体相关蛋白(SIGIRR)对肿瘤坏死因子(TNF-)受体相关因子6(TRAF 6)泛素化在急性肺损伤(ALI)在肺泡上皮细胞和肺泡巨噬细胞在体外的影响进行了评估。我们的研究结果发现,SIGIRR负调控TRAF 6泛素化,并且这种SIGIRR抑制可以增强肺泡上皮细胞(AECs)和肺泡巨噬细胞(AMCs)中的TRAF 6表达。SIGIRR敲低可能通过TRAF 6调节经典而非经典NF-κB信号通路增加NF-κ B B活性。TRAF 6和SIGIRR之间的这种调节可影响细胞因子分泌并加剧免疫应答; IL-8、NFKB 1和NFKBIA mRNA水平在SIGIRR过表达后降低。本研究揭示了SIGIRR对LPS/TLR-4信号通路相关的先天免疫应答负调控作用的分子机制,为临床治疗炎症性疾病提供了依据。
In this study, the effects of single immunoglobin IL-1 receptor-related protein (SIGIRR) on tumor necrosis factor- (TNF-) receptor-associated factor 6 (TRAF6) ubiquitination in acute lung injury (ALI) were evaluated in both alveolar epithelial cells and alveolar macrophage cells in vitro. Our results found that SIGIRR negatively regulated TRAF6 ubiquitination and such SIGIRR inhibition could enhance the TRAF6 expression in both alveolar epithelial cells (AECs) and alveolar macrophage cells (AMCs). SIGIRR knockdown may increase NF-κB activity via TRAF6 regulation by the classical but not the nonclassical NF-κB signaling pathway. Such modulation between TRAF6 and SIGIRR could affect cytokine secretion and exacerbate the immune response; the IL-8, NFKB1, and NFKBIA mRNA levels were reduced after SIGIRR overexpression. The current study reveals the molecular mechanisms of the negative regulatory roles of SIGIRR on the innate immune response related to the LPS/TLR-4 signaling pathway and provides evidence for strategies to clinically treat inflammatory diseases.
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