The Role Of SOD1 In Regulating Inflammatory Response Induced By MSU

Objective:As we all known that gout is closely related to MSU crystals,and one of the early events related to the onset of gout is oxidative stress.Oxidative state is triggered by the reactive oxygen species(ROS)and pro-inflammatory cytokines.The superoxide dismutase(SOD)family limits the potential toxicity of ROS by controlling the levels of them inside and outside the cell,and regulates various life activities through it’s signaling function.The main purpose of this study is to explore the molecular mechanism of SOD 1 in regulating inflammatory response induced by MSU.Methods:The peripheral blood samples of outpatient with gout and healthy people were collected from October 2020 to October 2021 in the Affiliated Hospital of North Sichuan Medical College and separated into serum and peripheral blood mononuclear cells(PBMCs).the levels of serum IL-1β were estimated via ELISA.The expression of SOD-dependent ROS signaling pathway related enzyme genes was further investigated by RT-PCR amplification of SOD 1,SOD2,CAT,GPX1.The expression levels of SOD 1,SOD2,CAT,GPX1 were analyzed by western blotting techniques.Murine BMDMs cells were transfected with non-specific siRNA(si-control)or si-SOD1 and all of them stimulated with a certain concentration of MSU crystals for 12 h.Following transfection,SOD1 gene,pro-inflammatory factors and chemokines expression was analyzed via RT-qPCR and western blot,such as IL-1β,IL-6,TNF-α,COX-2,INOS,NLRP3.Results:SOD1 gene expression was down regulated in gout patients,as well as acute gout is lower than that in intermittent gout.CAT,GPX1 gene expression were decreased in gout patients while SOD2 was upregulated.MSU-induced pro-inflammatory factors secretion was decreased by si-SOD1 treatment compared with the si-control treatment,such as IL-1β,IL-6,TNF-α,COX-2,INOS.Conclusion:SOD1 may participate in the MSU-induced inflammatory response through the regulation of oxidative stress and the activation of NLRP3 inflammasomes.SOD 1 may be a potential target for the treatment of acute gout arthritis.