SIGIRR过表达抑制LPS诱导的肺泡上皮细胞NF-κB的活化

SIGIRR overexpression inhibits LPS-induced NF-κB activation in alveolar epithelial cells

目的:研究单免疫球蛋白白介素1受体相关蛋白(SIGIRR)对脂多糖(LPS)刺激的肺泡上皮细胞核因子-κB信号通路的调节作用。方法:以LPS刺激人Ⅱ型肺泡上皮细胞A549。将含有SIGIRR cDNA全长的真核表达载体瞬时转染A549细胞,使SIGIRR在A549细胞过表达。用双萤光素酶报告系统检测LPS刺激后A549细胞NF-κB的转录活性,用ELISA法检测LPS刺激后细胞因子白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)以及白细胞介素-6(IL-6)的水平,对比转染与否对上述因子在A549细胞中释放水平的影响。结果:在A549细胞中,过表达SIGIRR可显著抑制NF-κB的转录活性,同时抑制LPS诱导的细胞因子IL-1β、TNF-α以及IL-6的表达。结论:SIGIRR过表达可以抑制LPS触发的肺泡上皮细胞中TLR4信号的转导,从而发挥减轻炎症反应、保护肺泡上皮细胞的作用。

AIM ： To investigate the effect of single immunoglobin IL - 1 receptor related protein （SIGIRR） on damage of alveolar epithelial cells in acute lung injury induced by lipopolysaccharide. METHODS ： The acute alveolar epithelial cell injury model was constructed by stimulation of A549 cells with LPS. In order to over - express SIGIRR, the A549 cells were transferred with eukaryotic expression vector containing full length SIGIRR cDNA. The transcriptional activity of NF - KB was measured by dual - luciferase reporter assay system. The concentrations of IL - 16, TNF - α and IL - 6 were detected by ELISA. The levels of these inflammatory factors between the transfected cells and untransfected cells were compared. RESULTS ： The over - expression of SIGIRR inhibited the transcriptional activity of NF - κB. The increases in IL - 1β, TNF - α and IL - 6 concentrations in alveolar epithelial cells induced by LPS were observed. CONCLUSION： SIGIRR in alveolar epithelial cells inhibits TLR4 signals triggered by LPS and attenuates the inflammatory reactions in alveolar epithelial cells, which plays a protective role against the acute damage of the alveolar epithelial cells.