The Role Of ZFP36L1 In Gouty Arthritis And Its Molecular Mechanism Of Regulation

Objective:The ZFP36 family of RNA-binding proteins was a negative regulator of many inflammatory responses,which was strongly expressed in a variety of inflammatory diseases and autoimmune diseases.The main purpose of this study is to explore the mechanism of ZFP36L1,one of the ZFP36 family,in the spontaneous remission of gout arthritis,in order to provide a new treatment idea for gout treatment.Methods:Collected in Affiliated Hospital of North Sichuan Medical College during 2019.10 2020.10 outpatient healthy human peripheral blood specimens,gout patients and medical center laboratory separation of serum and peripheral blood mononuclear cells(PBMCs).The expression levels of serum IL-1β and TGF-β were detected by ELISA,and the mRNA expression levels of ZFP36L1,TGF-β,IL-1β,IL-6 and TNF-α were detected by RT-qPCR.The expression differences between normal subjects and patients with gout were compared between the acute and intermittent periods.Human macrophage THP-1 and mouse macrophage RAW264.7 were cultured in the laboratory.After interfering the expression of THP-1-derived macrophage and RAW264.7 cell ZFP36L1,the mRNA expression levels of ZFP36L1,TGF-β,IL-1β,IL-6,HSP70,TNF-α,COX-2 and NOS2 were detected by RT-qPCR with certain concentration of MSU crystal stimulation.The expression levels of IL-1β and TGF-β in normal subjects,acute stage and intermittent stage patients and THP-1-derived macrophages were detected by ELISA,and the differences of expression were compared.Results:The expression level of ZFP36L1 in PBMCs of patients with gout was higher than that of normal controls,while the expression level of ZFP36L1 in PBMCs of patients with acute phase was higher than that of patients with intermittent phase.Different concentrations of MSU crystals stimulated THP-1-derived macrophages,and the expression level of ZFP36L1 was also increased in different degrees.After interfering with the expression of ZFP36L1 in THP-1-derived macrophages and RAW264.7 cells,the expression levels of inflammatory factors such as IL-1β and NOS2 were significantly increased,while the expression levels of anti-inflammatory factors such as TGF-β were decreased.Conclusion:ZFP36L1 involved in gouty arthritis;In the inflammatory response induced by MSU crystals,ZFP36L1 can regulate the inflammatory response by regulating the expression of inflammation-related genes,and ZFP36L1 may be a potential target for the treatment of acute gout arthritis.