■含有无菌α和TIR基序的1(Sarm1)已知为炎症反应的负调节因子。然而,其在炎症性肠病(IBD)中的作用尚不清楚。
■本研究旨在探讨Sarm1在IBD中的作用及其潜在机制。建立了Sarm1和肿瘤坏死因子(TNF)受体相关因子3(TRAF3)敲除(KO)小鼠。
■使用葡聚糖硫酸钠(DSS)诱导结肠炎。分离骨髓来源的巨噬细胞(BMDM),并用脂多糖(LPS)或胞苷磷酸鸟苷(CpG)刺激。通过ELISA测量炎性细胞因子。qPCR和蛋白质印迹用于确定mRNA和蛋白质表达的水平,分别。
■研究表明,在溃疡性结肠炎患者中,Sarm1的表达降低与IBD的严重程度相关,以及DSS诱导的小鼠模型中促炎细胞因子的减少。进一步观察到Sarm1KO增强了动物和体外细胞模型中促炎细胞因子的诱导。巨噬细胞中的Sarm1缺乏增加了DSS诱导的小鼠模型中结肠炎的严重程度。此外,Sarm1调节TRAF3募集到髓样分化初级反应蛋白88(MyD88),进而控制MYD88介导的炎症反应。
■总之,我们的数据表明,Sarm1通过调节TRAF3募集来控制IBD中MYD88介导的炎症反应.
1.Sarm1KO增强动物和体外细胞模型中促炎细胞因子的诱导。巨噬细胞中的Sarm1缺乏增加小鼠模型中结肠炎的严重程度。Sarm1规范了对MyD88的TRAF3招募。
UNASSIGNED: Sterile alpha and TIR motif-containing 1 (
Sarm1) is known as a negative regulator of inflammatory responses. However, its role in inflammatory bowel disease (IBD) is still unclear.
UNASSIGNED: This study aimed to explore the function of
Sarm1 in IBD and its underlying mechanisms. Sarm1 and tumor necrosis factor (TNF) receptor associated factor 3 (TRAF3) knockout (KO) micewere established.
UNASSIGNED: The colitis was induced using dextran sulfate sodium (DSS). Bone marrow-derived macrophages (BMDMs) were isolated and stimulated with lipopolysaccharides (LPS) or cytidine phosphate guanosine(CpG). Inflammatory cytokines were measured viaELISA. qPCR and Western blotting were used to determine the levels of the mRNA and protein expression, respectively.
UNASSIGNED: It was demonstrated that reduced expression of Sarm1 was correlated with the severity of IBD in ulcerative colitis patients, and also with the reduction of pro-inflammatory cytokines in the mouse model induced by DSS. It was further observed that Sarm1 KO enhanced the induction of pro-inflammatory cytokines in both animal and in vitro cell models.
Sarm1 deficiency in macrophages increased the severity of colitis in the mouse model induced by DSS. Moreover, Sarm1 regulatedTRAF3 recruitment to myeloid differentiation primary response protein 88 (MyD88), which in turn controlled the MYD88-mediated inflammatory responses.
UNASSIGNED: In summary, our data suggest that Sarm1 controls the MYD88-mediated inflammatory responses in IBD via its regulation of TRAF3 recruitment.
1. Sarm1 KO enhances the induction of pro-inflammatory cytokines in both animal and in vitro cell models.2.
Sarm1 deficiency in macrophages increases the severity of colitis in the mouse model.3.
Sarm1 regulates TRAF3 recruitment to MyD88.