UCHL1调控NF-κB信号通路在单核细胞驯化免疫中的作用OA北大核心CSTPCD

Aim To investigate the role and mecha-nism of deubiquitinating enzymes in trained immunity of monocytes.Methods Q-PCR was used to detect the expression of deubiquitinating enzyme-related genes in trained monocytes,the effect of deubiquitinating en-zyme on the secretion of tumor necrosis factor-α(TNF-α)in trained 0monocytes was detected by ELISA,and the effect of deubiquitinating enzyme on the NF-κB sig-naling pathway was determined by dual luciferase re-porter assay system.The dual luciferase reporter assay system was also used to determine the effect of UCHL1 expression on NF-κB signaling pathway,the interaction with the NF-κB pathway,and the effect of enzyme ac-tivity on the NF-κB pathway.ELISA was used to verify the effect of UCHL1 on the secretion level of TNF-α in trained immunity.Results The results showed that the expression levels of USP2,UCHL1,OTUB2 and OTUD4 significantly increased in training of mono-cytes.The deubiquitinating enzyme inhibitor could sig-nificantly inhibit the secretion of TNF-α in trained monocytes.USP2,UCHL1,OTUB2 and PSMD14 could significantly activate the NF-κB signaling path-way,and UCHL1,which had the most significant effect on NF-κB,was selected for further investigation.It was shown that UCHL1 expression could affect the activation of NF-κB pathway;UCHL1 promoted the ac-tivation of NF-κB induced by IKB-α,IKK-α or IKK-β,and the regulation of UCHL1 on the NF-κB pathway depended mainly on its ubiquitin hydrolase activity.Furthermore,UCHL1 inhibitors could greatly reduce the trained immunity of monocytes.Conclusion The immune complexes of patients with autoimmune disea-ses can be domesticated monocytes that increase their sensitivity by regulating the UCHL1-activated NF-κB pathway.