title: Differential expression of the TL1A/DcR3 system of TNF/TNFR-like proteins in large vs. small intestinal Crohn's disease.
abstract: BACKGROUND
  TNF-like cytokine 1A provides co-stimulatory signals to activated lymphocytes through binding to death-domain receptor-3. Decoy receptor-3 inhibits death-domain receptor-3 signalling, rendering immunocytes resistant to apoptosis. These functions may be important for the pathogenesis of Crohn's disease.
  
  
  OBJECTIVE
  To study the mucosal and systemic expression of Decoy receptor-3 and TNF-like cytokine 1A in Crohn's disease, in relation to disease activity, localization, and response to treatment.
  
  
  METHODS
  Soluble Decoy receptor-3 and TNF-like cytokine 1A were measured by ELISA in active or quiescent Crohn's disease. Relative mRNA expression in non-affected and inflamed intestinal mucosa was determined by real-time RT-PCR.
  
  
  RESULTS
  We found significant upregulation of Decoy receptor-3 and its ligands TNF-like cytokine 1A and FasL in inflamed intestinal mucosa of Crohn's disease patients. During active disease, Decoy receptor-3 and TNF-like cytokine 1A were detected in the serum in the majority of patients. Intestinal inflammation was strongly associated with these elevations as they were absent during remission and significantly reduced with anti-inflammatory treatment. Regional diversity was observed as Decoy receptor-3 was upregulated in colonic and ileal sites, whereas TNF-like cytokine 1A was preferentially induced in the large bowel mucosa and systemic circulation of patients with colonic involvement.
  
  
  CONCLUSIONS
  TNF-like cytokine 1A and Decoy receptor-3 are upregulated during active Crohn's disease and may participate in disease pathogenesis and offer novel therapeutic opportunities.
authors: GI Division - 1st Department of Propaedeutic and Internal Medicine, "Laikon" General Hospital, Athens University Medical School, 17 Agiou Thoma st., 11527 Athens, Greece. gbamias@gmail.com
authors: Giorgos
authors: G
authors: Bamias
authors: Garyfallia
authors: G
authors: Kaltsa
authors: Spyros I
authors: SI
authors: Siakavellas
authors: Michalis
authors: M
authors: Gizis
authors: George
authors: G
authors: Margantinis
authors: Evanthia
authors: E
authors: Zampeli
authors: Irene
authors: I
authors: Vafiadis-Zoumboulis
authors: Spyros
authors: S
authors: Michopoulos
authors: George L
authors: GL
authors: Daikos
authors: Spiros D
authors: SD
authors: Ladas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007420:Intestine, Large / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000097:blood / Q000378:metabolism*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000097:blood / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15