High intestinal and systemic levels of decoy receptor 3 (DcR3) and its ligand TL1A in active ulcerative colitis.
Decoy receptor-3 (DcR3) is a member of the TNF receptor superfamily of proteins, which has been implicated in anti-apoptotic and anti-inflammatory pathways, via binding to TL1A, LIGHT and Fas-L. The role of the TL1A/DcR3 ligand/receptor pair in ulcerative colitis (UC) has not been studied. We investigated the systemic (peripheral blood) and local (large intestine) expression of DcR3 and TL1A in 64 patients with UC and 56 healthy controls. DcR3 serum concentrations were highly elevated in patients with active UC (P<0.0001 vs. healthy controls). This elevation was clearly related to the presence of intestinal inflammation as it was less frequently observed in patients in remission (P=0.003 vs. active UC) whereas effective treatment resulted in disappearance or significant decrease of serum DcR3 (P=0.006 vs. pre-treatment). Furthermore, DcR3 mRNA transcripts were significantly elevated in inflamed areas of the colon (P=0.002 vs. non-affected of the same patient). In addition to DcR3 elevation, we found increased circulating levels of TL1A in patients with either active or inactive UC in comparison to healthy controls (P<0.001 for both). We conclude that elevated serum DcR3 may serve as an indicator of active colonic inflammation in patients with UC. TL1A/DcR3-mediated pathways may participate in the pathogenesis of UC.
Bamias
Giorgos
G
Gastroenterology Division - First Department of Propaedeutic and Internal Medicine, Laikon General Hospital, Athens University Medical School, 17 Agiou Thoma st., 11527, Athens, Greece. gbamias@gmail.com
Kaltsa
Garyfallia
G
Siakavellas
Spyros I
SI
Papaxoinis
Kostis
K
Zampeli
Evanthia
E
Michopoulos
Spyros
S
Zouboulis-Vafiadis
Irene
I
Ladas
Spiros D
SD
D000293:Adolescent; D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000097:blood* / Q000378:metabolism* / Q000628:therapy; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000032:analysis* / Q000097:blood / Q000235:genetics / Q000378:metabolism; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000032:analysis* / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D055815:Young Adult
D053323:Receptors, Tumor Necrosis Factor, Member 6b; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein