PDF(Pubmed)
Abstract：
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and the production of autoantibodies. Previous studies have indicated an association between high-salt diets (HSD) and an increased risk of RA, yet the underlying mechanisms remain unclear. Macrophage pyroptosis, a pro-inflammatory form of cell death, plays a pivotal role in RA. In this study, we demonstrate that HSD exacerbates the severity of arthritis in collagen-induced arthritis (CIA) mice, correlating with macrophage infiltration and inflammatory lesions. Given the significant alterations observed in macrophages from CIA mice subjected to HSD, we specifically investigate the impact of HSD on macrophage responses in the inflammatory milieu of RA. In our in vitro experiments, pretreatment with NaCl enhances LPS-induced pyroptosis in RAW.264.7 and THP-1 cells through the p38 MAPK/NF-κB signaling pathway. Subsequent experiments reveal that Slc6a12 inhibitors and SGK1 silencing inhibit sodium-induced activation of macrophage pyroptosis and the p38 MAPK/NF-κB signaling pathway, whereas overexpression of the SGK1 gene counteracts the effect of sodium on macrophages. In conclusion, our findings verified that high salt intake promotes the progression of RA and provided a detailed elucidation of the activation of macrophage pyroptosis induced by sodium transportation through the Slc6a12 channel.
摘要：
类风湿性关节炎（RA）是一种慢性系统性自身免疫性疾病，其特征是滑膜炎症和自身抗体的产生。先前的研究表明，高盐饮食（HSD）与RA风险增加之间存在关联。然而，潜在的机制仍不清楚。巨噬细胞焦亡，一种促炎症的细胞死亡形式，在RA中起着举足轻重的作用。在这项研究中,我们证明HSD会加剧胶原诱导性关节炎（CIA）小鼠关节炎的严重程度，与巨噬细胞浸润和炎性病变有关。鉴于在接受HSD的CIA小鼠的巨噬细胞中观察到的显着变化，我们专门研究了HSD对RA炎症环境中巨噬细胞反应的影响.在我们的体外实验中，NaCl预处理通过p38MAPK/NF-κB信号通路增强LPS诱导的RAW.264.7和THP-1细胞的焦凋亡。随后的实验表明，Slc6a12抑制剂和SGK1沉默抑制钠诱导的巨噬细胞焦亡激活和p38MAPK/NF-κB信号通路，而SGK1基因的过表达抵消了钠对巨噬细胞的影响。总之,我们的研究结果证实了高盐摄入促进RA的进展,并详细阐明了钠通过Slc6a12通道转运诱导的巨噬细胞焦亡的激活.
