Differential expression of the TL1A/DcR3 system of TNF/TNFR-like proteins in large vs. small intestinal Crohn's disease

• Published in: Digestive and liver disease Vol. 44; no. 1; pp. 30 - 36
• Main Authors: Bamias, Giorgos, Kaltsa, Garyfallia, Siakavellas, Spyros I, Gizis, Michalis, Margantinis, George, Zampeli, Evanthia, Vafiadis-Zoumboulis, Irene, Michopoulos, Spyros, Daikos, George L, Ladas, Spiros D
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.01.2012
• Subjects: Adolescent; Adult; Aged; Crohn Disease - metabolism; Crohn Disease - pathology; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Gastroenterology and Hepatology; Humans; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestine, Large - metabolism; Intestine, Large - pathology; Intestine, Small - metabolism; Intestine, Small - pathology; Male; Middle Aged; Mucosal inflammation; Real-Time Polymerase Chain Reaction; Receptors, Tumor Necrosis Factor, Member 6b - blood; Receptors, Tumor Necrosis Factor, Member 6b - metabolism; RNA, Messenger - metabolism; Tumor Necrosis Factor Ligand Superfamily Member 15 - blood; Tumor Necrosis Factor Ligand Superfamily Member 15 - metabolism; Tumour necrosis factor receptor superfamily; Tumour necrosis factor superfamily; Up-Regulation; Young Adult; Cytokines; Tumour necrosis factor superfamily; Mucosal inflammation; Tumour necrosis factor receptor superfamily
• ISSN: 1590-8658; 1878-3562
• DOI: 10.1016/j.dld.2011.09.002

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. Aims 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.