The Mechanism Underlying ATP-P2X7R Regulation Of Acute Gouty Arthritis

Background Gout is an inflammatory disease,cytokine IL-1 beat and other cytokines is believed to be a major cytokine involved in the pathogenesis of acute gouty arthritis. Previous study showed monosodium urate crystals(MSU) may through a variety of ways to stimulate IL-1β secretion,and participate in the onset of gout.But the MSU is the pathogenic signal theory can not explain the clinical phenomenon appears never part of hyperuricemia in patients with gout,There are other tips pathogenic signal. Present study suggests that, IL-1 betasecretion is regulated by multiple signaling pathways, one concern is the P2X7 R receptorsignal pathway in ATP induced regulation IL-1beta secretion.Research has shown that ATP can be induced by IL-1 beta secretion of monocytesurface P2X7 R stimulation, may play an important role in the pathogenesis of gout. A predisposing factor in gouty arthritisattacks, such as alcohol, binge eating, there are sharp fluctuations in ATP, suggesting that ATP-P2X7R-IL-1βpathway may play an important role in the pathogenesis of gouty arthritis.Our research group proposed according to the above inflammatory cytokine regulatory pathway mechanism: gouty arthritis and ATP activation of P2X7 signaling system, P2X7 R may be the key to the potential for acute gouty arthritis regulator; discusses thepathogenesis of acute gouty arthritis from molecular mechanisms, to find a new way for thedisease prevention and control. This study aims to explore with ATP-P2X7R-IL-1 beta for the mechanism of acute attack of gout target regulation, will provide a theoretical basis for the pathogenesis and clinical treatment of gout perfect.Objective To investigate the role of ATP-P2X7R-IL-1β in gouty arthritis.Method Peripheral white blood cells from the patients with hyperuricemia or gout were cultured with MSU or MSU+ATP. IL-1β、IL-6、IL-8、IL-10、IL-12、TNF in supernatantwas examined with enzyme linked immunosorbent assay(ELISA) and Cytometric Bead Array(CBA). CD14+P2X7R+ cells were detected using flow cytometry.T-test, non-parametric test, paired-samples t test, Pearson correlation analysis were used for statistical analysis.Results 1. After the stimulation by MSU alone, there was no differences of the concentration of IL-1β、IL-6、IL-8、IL、TNF between the gout and hyperuricemia groups(Z=-1.334,P>0.05;Z=-0.338,P>0.05;t=-0.998,P>0.05;Z=-1.186,P>0.05). However with the stimulation by MSU+ATP,gout patients had higher concentration of IL-1β compared to the hyperuricemia patients(Z=-2.081,P=0.037),but there was no differences of the concentration of IL-6、IL-8、TNF between the gout and hyperuricemia groups(Z=-1.356, P > 0.05; Z=-1.366, P > 0.05; Z=-1.239, P > 0.05). 2. In hyperuricemia group,the concentrations of IL-1β、IL-6、IL-8、TNF were not different between MSU and MSU+ATP stimulation(Z=-1.429,P>0.05;Z=-1.373,P>0.05;t=-1.077,P>0.05;Z=-1.287,P>0.05), while in gout group, the concentration was significantly higher after the stimulation by MSU+ATP than MSU(Z=-2.548,P<0.05;Z=-2.678,P<0.05;t=-2.215,P<0.05;Z=-3.233,P<0.05). 3. IL-10 and IL-12 were not detected in cell culture fluid. 4. The frequency of CD14+P2X7R+ cells in the peripheral blood of the patients with gout was significantly higher than that of patients with hyperuricemia(t=-3.567, P<0.05). 5. No correlation was found between IL-1 β concentration in supernatant and the frequency of CD14+P2X7R+ cells(r=-0.504,P>0.05;r=-0.379,P>0.05)Conclusion ATP is involved in the pathogenesis of gout, is an important signal in the onset of acute gouty arthritis;Functional state of the receptor P2X7 R may be an important factor in the decision of the gout.