Expression And Significance Of Notch Signal Pathway And Target Gene In Juvenile Idiopathic Arthritis

ObjectiveTo analyze the relationship between Notch signaling pathway and levels of lymphocytes and cytokines in juvenile idiopathic arthritis(JIA);Moreover,this study to explore the influence and mechanism of Notch signaling pathway on B10 cell differentiation in collagen induced arthritis(CIA)mice,and blocking the Notch signaling pathway to analyze the level of cytokines.To investigate the activiation of Notch signaling and its role in the pathogenesis of JIA and provide a new target for the treatment of juvenile idiopathic arthritis.Methods(1)35 pediatric patients with JIA and 15 healthy children were included in the study.The expression of Notch signaling molecules in PBMC from JIA group and control group were determined by RT-qPCR.The levels of cytokines IL-1?,IL-10,IL-6,IL-17,TGF-? and IL-4 were detected by ELISA.(2)The frequency of B10 in splenic mononuclear cells and the levels of T helper17 cells were examined in CIA mice by flow cytometry.ELISA was used to detect plasma IL-10,IL-1?,TGF-?,IL-17 A and IL-4 of CIA group and normal mice.DAPT was used in B10 cell culture and then assessed the Notch signaling mRNA and the level of cytokines.Results(1)Compared with control group,the JIA group showed the Notch2 and HES1 expression levels were increased significantly(P<0.05).The target gene HES1 was positively correlated with CD3+T cells absolute count.(P<0.05);the patient group showed a significantly increased level of IL-10,IL-6,IL-1?,IL-17 and TGF-?(P<0.05)and no significantly levels of IL-4.The expression level of IL-10 was negatively correlated with the absolute number of T/B/Th/ suppressor T lymphocytes(p<0.05).(2)The frequency of B10 cell and Th17 cell were increased significantly in CIA group compared with normal group.The levels of plasma IL-1? and IL-17 were significantly increased,and IL-10,IL-4 and TGF-? were significantly decreased.In B10 cell the Notch1 receptor and Jagged1 ligand were increased,after co-culturing B10 with DAPT,the the Notch1 receptor and Jagged1 ligand were decreased,and the levels of plasma IL-10,IL-6,IL-17,TGF-? and TNF-? were significantly decreased.ConclusionOur present study demonstrates that the imbalance between Notch pathway and lymphocyte and cytokines in children with juvenile idiopathic arthritis may play an important role in the pathogenesis of JIA;Blocking the Notch signaling pathway can affect the development of B10 cell and down regulate the level of cytokines,which is helpful to prevent the progression of joint disease,and provide a new theoretical basis for further study of the role of Notch signaling pathway in juvenile idiopathic arthritis.