Expressions and significance of Notch signal pathway and target gene in children with juvenile idiopathic arthritis

Abstract

Objective To analyze the relationship between Notch signaling pathway and levels of lymphocytes and cytokines in children with juvenile idiopathic arthritis(JIA), and to explore its role in the pathogenesis of JIA. Methods Thirty-five pediatric patients with JIA [males 20 cases, females 15 cases; aged (6.5±4.0) years old, (0.83-15.00 years old)]and 15 healthy children [males 6 cases, females 9 cases; aged (5.0±2.9) years old, (1.0-11.0 years old)]from November 2015 to February 2016 in Guangzhou Women and Children′s Medical Center were included in the study. The JIA group were divided into the systemonset JIA(So-JIA) group (22 cases) and psoriatic JIA(p-JIA) group (13 cases, polyarthritis 7 cases and oligoarthritis 6 cases). The expressions of Notch signaling′s receptor, ligand and target gene mRNA in peripheral blood monouclear cells (PBMC) from the JIA group and the control group were determined by quantitative real-time PCR.The levels of cytokines interleukin (IL) -1β, IL-10, IL-6, IL-17, IL-4 and transforming growth factor-β (TGF-β) were detected by enzyme-linked immunosorbent assay. Results Compared with the healthy control group, the Notch2 receptors (1.6±3.2 vs. 0.4±0.3) expression level, Jagged1 ligand (44.0±79.0 vs. 11.3±1.2) expression levels and the levels of target gene HES1(0.4±0.3 vs. 0.1±0.1) mRNA in the JIA group showed a significant increase, and the differences were all statistically significant (all P<0.05 ). Compared with the healthy control group, the JIA group showed an increased level of IL-1β [(182.22±309.13) ng/L vs. (54.71±20.33) ng/L], IL-10 [(32.99±34.28) ng/L vs. (22.68±4.56) ng/L], IL-6 [(100.48±305.57) ng/L vs. (13.98±2.78) ng/L], IL-17 [(9.11±17.57) ng/L vs. (2.42±0.29) ng/L] and TGF-β [(14.37±9.33) ng/L vs. (5.49±4.49) ng/L], and there were statistically significant differences (all P<0.05) .The expression level of HES1 mRNA was positively correlated with STAT3 mRNA in the So-JIA group (r=0.573, P<0.05). The expression level of HES1 mRNA was positively correlated with CD3+ T(r=0.528), CD19+B(r=0.480), CD3+ CD4+ TH(r=0.457) and CD16+CD56+NK(r=0.598) cell absolute count in the So-JIA group (all P<0.05). The expression level of HES1 mRNA was positively correlated with CD3+ T cell absolute count in the p-JIA group(r=0.577, P<0.05). Conclusion Imbalance between Notch pathway and lymphocytes and cytokines in children with JIA may play an important role in the pathogenesis of JIA. Key words: Juvenile idiopathic arthritis; Notch pathway; Lymphocytes; Cytokines