title: 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.
authors: Division of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University). 145 Middle Shandong Rd, Shanghai 200001, China.
authors: Jun
authors: J
authors: Shen
authors: Yu-qi
authors: YQ
authors: Qiao
authors: Zhi-hua
authors: ZH
authors: Ran
authors: Tian-rong
authors: TR
authors: Wang
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D048008:TNF Receptor-Associated Factor 3 / Q000097:blood / Q000235:genetics; D048015:TNF Receptor-Associated Factor 5 / Q000097:blood / Q000235:genetics; D015854:Up-Regulation
chemical_list: D048008:TNF Receptor-Associated Factor 3; D048015:TNF Receptor-Associated Factor 5; C090656:TRAF3 protein, human
keywords: Crohn's disease; TRAF3; TRAF5; Ulcerative colitis.