The Role Of Alpha2B-Adrenergic Receptor In Gout

Background:Gout is one of the most common metabolic disorders in human.An acute inflammatory response is caused by the Monosodium Urate(MSU)formation by excessive blood uric acid concentration depositing in the articular cavity.Then,mononuclear cells/macrophages phagocytose MSU to induce the production of IL-1β,resulting in the infiltration of a large number of inflammatory cells and the production of multiple inflammatory factors.Previous studies have shown that the disease activity is closely associated with sympathetic nervous system(SNS)tone.It has been reported that,α2B-adrenergic receptor(α2BAR),a subtype of adrenergic receptor,plays a critical role in many diseases.However,the role of α2BAR in the pathogenesis of gout remains unclear.Methods:Here,we assessed the role of α2BAR in the monosodium urate crystals(MSU)induced peritonitis that mimics human gout by using the α2BAR-overexpressing mice(α2BAR-Tg)and wild type mice(Wt).Peritoneal immersion cells(PECs)were detected by a Flowsight?cytometer,and the cytokines in the peritoneal lavage fluids were detected by ELISA.Moreover,we detected the activity of caspase-1.Then,we used neutrophils migration experiment to further investigated the role α2B AR played in gout.Results:We found that the number of recruited neutrophils was significantly increased in the a2BAR-Tg mice after MSU treatment,when compared with wild type mice.In contrast,the number of macrophages was not changed.Importantly,there is no difference in the IL-1β levels and caspase-1 activity between wild type and a2BAR-Tg mice in the gout animal model.Notably,the enhanced neutrophil migration in α2BAR-Tg mice was dependent on the α2BAR overexpression in neutrophils,but not resulted from other tissues or cells with α2BAR overexpression.Futhermore,it is also not related to the neutrophil expression of chemokine receptor CXCR2.Conclusion:In conclusion,our in vivo and in vitro results indicated that overexpression ofα2BAR increased the migration of neutrophils to the site of inflammation,and played a critical role in MSU-induced inflammation.These results may provide a new target for further research and treatment of gout.