The Role Of Gq Alpha In The Pathogenesis Of Acute Gouty Arthritis And Its Potential Mechanism

Background:Gouty Arthritis(GA)is a kind of acute inflammation which is caused by the Monosodium Urate(MSU)depositing in the articular cavity and is always accompanied by amounts of cytokine synthesis.It has been reported that the central leukocytes involved in GA are monocyte/macrophage and neutrophil,and the major cytokine is IL-1β.However,the detailed inflammatory mechanism in GA is still unclear.Gaq is the function subunit of G protein q and regulates multiple aspects of leukocyte function.Yet it has not reported whether Gaq participants in genesis or development of GA.Methods:the relative expression of GNAQ in WBC of GA and HC is detected by RT-PCR.The correlation between the relative expression of GNAQ and clinical data is analyzed.Then,the mouse air pouch model is used to confirm whether Gaq taking part in the regulation of acute inflammatory reaction induced by MSU.Finally,the mouse BMDM is cultured to preliminarily study whether Gαq participants in GA pathogenesis by regulating the cytokines production and phagocytic function of BMDM.Results:by analyzing clinical data,we find the relative expression of GNAQ in WBC is lower in GA compared with HC and is correlated with the level of UA,ESR and CRP.These results indicate that Gaq may play a role in the progression of GA.And then,we find the number of recruited leukocytes and the amount of cytokines production is higher in the Gnaq-/-mouse air pouch model compared with WT mouse model.So these results suggest that Gaq negatively control the inflammation induced by MSU.Furthermore,we find that Gnaq-/-BMDM secrete more cytokines and express stronger NLRP3 signal than WT BMDM.Also,the phagocytic function and ROS expression of Gnaq-/-BMDM is greater than WT BMDM’s.Concludions:the clinical data and experiment results show that Gaq participants in GA pathogenesis through inhibiting the phagocytic function,ROS exprssion,cytokines production and NLRP3 signal path way of macrophage.So this research explains the role of G protein q in the inflammatory reaction induced by MSU and supplements the pathogenesis of GA.It may provide a new target in GA treatment.