RCAN1促进沙门菌诱导的NLRC4炎性体活化

RCAN1 promotes Salmonella-induced NLRC4inflammasome activation

以野生型(WT)小鼠和钙调磷酸酶调节因子1(RCAN1)基因缺失(RCAN1^-/-)小鼠骨髓来源巨噬细胞为模型,探究RCAN1对沙门菌诱导的炎性体活化的影响。用沙门菌和沙门菌鞭毛蛋白处理细胞诱导炎性体活化后,采用ELISA方法检测细胞培养上清中IL-1β和TNF-α的分泌,采用Western blot方法检测caspase-1、IL-1β的剪切成熟以及ASC的寡聚化,分析RCAN1对炎性体活化影响。结果显示,RCAN1能够显著促进沙门菌诱导的IL-1β的分泌,但对TNF-α的分泌无影;能够促进caspase-1和IL-1β前体的剪切与成熟、促进ASC寡聚化。沙门菌鞭毛蛋白能够诱导NLRC4炎性体活化。鞭毛蛋白处理后,RCAN1能够促进IL-1β的分泌,但不影响TNF-α的分泌。结果表明,RCAN1能够促进沙门菌诱导的NLRC4炎性体活化信号。

This study investigated the effects of RCAN1 on Salmonella-induced inflammasome activation using bone marrow-derived macrophages(BMDM)from wild-type mice(WT)and RCAN1 deficient(RCAN1^-/-)mice.This study cells were treated with Salmonella typhimurium or flagellin induced inflammatory activation,and then the secretion of IL-1β and TNF-α in supernatant,ASC oligomerization and maturation of caspase-1 and IL-1β were detected for evaluating the effect of RCAN1on inflammatory activation.The results showed that RCAN1 could significantly promote Salmonella-induced IL-1β secretion without affecting the secretion of TNF-α,increase ASC oligomerization and maturation of caspase-1 and IL-1β.Salmonella flagellin can induce NLRC4inflammasome activation.After flagellin treatment,RCAN1deficiency resulted in reduced IL-1β secretion in BMDM treated with flagellin,however,the secretion of TNF-α was not affected.Collectively,these results indicated that RCAN1 promotes Salmonella-induced NLRC4 inflammasome activation.