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.

中文翻译：

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SIGIRR对TRAF6泛素化在急性肺损伤中的负面影响。

在这项研究中，评估了两种肺泡上皮细胞中单个免疫球蛋白IL-1受体相关蛋白（SIGIRR）对急性肺损伤（ALI）中肿瘤坏死因子-（TNF-）受体相关因子6（TRAF6）泛素化的影响。细胞和肺泡巨噬细胞体外。我们的研究结果发现SIGIRR负调节TRAF6泛素化，并且这种SIGIRR抑制作用可以增强TRAF6在肺泡上皮细胞（AEC）和肺泡巨噬细胞（AMC）中的表达。SIGIRR敲低可能增加NF- κ通过经典但不是非经典的NF-经由TRAF6调节B活性κB信号通路。TRAF6和SIGIRR之间的这种调节可能会影响细胞因子的分泌并加剧免疫反应。SIGIRR过表达后，IL-8，NFKB1和NFKBIA mRNA水平降低。当前的研究揭示了SIGIRR在与LPS / TLR-4信号通路相关的先天免疫应答中负调控作用的分子机制，并为临床治疗炎性疾病的策略提供了证据。