Up-regulation and Pre-activation of TRAF3 and TRAF5 in Inflammatory Bowel Disease

Abstract

Objective: TRAF3 and TRAF5 share a common ancestral gene, and interact as essential components of signaling pathways in immunity. TRAF3 and TRAF5 are overexpressed in the colon of rat/mouse models with colitis. However, the expressions of TRAF3 and TRAF5 in patients with inflammatory bowel disease have not been elucidated. The aim of the present study is to explore the potential roles of TRAF3 and TRAF5 in patients with inflammatory bowel disease.Methods: Plasma levels of TRAF3 and TRAF5 proteins were detected by Enzyme-linked Immunosorbent Assay (ELISA). Colonic expression of TRAF3 and TRAF5 proteins was detected by western blot analysis. Quantitative Real-time PCR (qRT-PCR) was applied for gene expression. Inflamed intestinal mucosa and non-inflamed intestinal mucosa in patients with inflammatory bowel disease and normal mucosa was analyzed from healthy controls.Results: The plasma levels of TRAF3 and TRAF5 were significantly higher both in patients with Crohn's disease and ulcerative colitis than in healthy controls. Only soluble TRAF5 showed a weak correlation with endoscopic disease activity index (Baron score) in patients with ulcerative colitis (spearman's r=0.358, P=0.022). Gene expressions of TRAF3 and TRAF5 in peripheral blood mononuclear cells were significantly higher both in patients with Crohn's disease and ulcerative colitis than in healthy controls (all P<0.0001). Gene and protein expressions of TRAF3 and TRAF5 were significantly higher in inflamed colonic mucosa of patients with Crohn's disease and ulcerative colitis than in non-inflamed colonic mucosa and normal mucosa of healthy controls (all P<0.0001). Furthermore, gene and protein expressions of TRAF3 and TRAF5 were also significantly higher in non-inflamed colonic mucosa of patients with Crohn's disease and ulcerative colitis than in normal mucosa of healthy controls.Conclusions: TRAF3 and TRAF5 are overexpressed in inflammatory bowel disease. Although the endoscopic appearance can be normal, TRAF3 and TRAF5 pre-activation can be detected in non-inflamed colonic segments.

TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells

“…Furthermore, in human inflammatory bowel disease (IBD) specimens, the mRNA level of EZH2 was negatively correlated with that of TRAF2 or TRAF5, suggesting that the decreased EZH2 expression in IBD patients causes augmented TNF-a-induced NF-kB signaling mediated by TRAF2 and TRAF5. In support of this, the expression of TRAF2 and TRAF5 was upregulated in the inflamed colonic tissues of IBD patients (38,39). In addition, the overexpression of TRAF2 or TRAF5 might be involved in colon cancer development (40,41).…”

Berberine prevents the apoptosis of mouse podocytes induced by TRAF5 overexpression by suppressing NF-κB activation

“…It has previously been reported that soluble TRAF5 levels are increased in plasma and peripheral blood mononuclear cells from patients with Crohn's disease and ulcerative colitis (21). other studies have implicated TRAF5 in carcinogenesis attributable to increased levels in splenic marginal zone lymphoma (22) and Hodgkin-Reed-Sternberg cells (23).…”

TRAF5-mediated Lys-63-linked Polyubiquitination Plays an Essential Role in Positive Regulation of RORγt in Promoting IL-17A Expression

“…It has been well established that TRAF5 is involved in the pathogenesis of several inflammatory and autoimmune diseases. The expression levels of TRAF5 increase in patients suffering from inflammatory bowel disease, and there is a weak correlation between TRAF5 and endoscopic disease activity index in patients with ulcerative colitis (16). Also, TRAF5 has been identified as a strong candidate for the rheumatoid arthritis susceptibility gene in the British population (17), and it is involved in the development of acute anterior uveitis (18), according to genetic polymorphism analysis in Han Chinese.…”