LncSLED1 inhibits monosodium urate-induced macrophage inflammation by promoting Cosmc methylation to upregulate CA72-4

Introduction The core event of gout is intensified macrophage inflammation. Our preliminary research found that carbohydrate antigen 72-4 (CA72-4) secreted by monosodium urate (MSU)-induced human synovial cells (HFLS) could upregulate transforming growth factor 1 (TGF-1) in macrophages. Herein, the mechanism of MSU-induced abnormal upregulation of CA72-4 in HFLS was investigated. Material and Methods Cell viability was assessed by CCK-8 assay. The secretion levels of cytokines and CA72-4 were measured by ELISA. Methylation-specific PCR (MSP) was employed to detect the methylation level of the Cosmc promoter. The molecular interactions were analyzed by RIP and ChIP assays. Results Our results demonstrated that CA72-4 derived from MSU-treated HFLS markedly inhibited MSU-induced macrophage inflammation. Mechanistically, MSU-induced lncSLED1 upregulation in HFLS reduced MSU-induced macrophage inflammation by promoting CA72-4 secretion. In addition, lncSLED1 facilitated CA72-4 secretion in MSU-treated HFLS by promoting the methylation level of the Cosmc promoter through recruiting EZH2. As expected, Cosmc silencing in HFLS reversed the weakening effect of lncSLED1 downregulation on mCM (the conventional medium from MSU-treated HFLS)-induced inhibition of MSU-induced macrophage inflammation. Conclusions MSU elevated lncSLED1 in HFLS, boosting CA72-4 secretion by increasing Cosmc promoter methylation via EZH2 recruitment, thus reducing MSU-induced macrophage inflammation.