Disease-related expression of the IL6/STAT3/SOCS3 signalling pathway in ulcerative colitis and ulcerative colitis-related carcinogenesis
- 18 November 2009
- Vol. 59 (2), 227-235
- https://doi.org/10.1136/gut.2009.184176
Abstract
Background Mouse models have shown that interleukin (IL)6 stimulates survival, proliferation and progression to cancer of intestinal epithelial cells via activation of signal transducers and activators of transcription 3 (STAT3). Objective To investigate the expression of IL6/phosphorylated STAT3 (p-STAT3)/suppressor of cytokine signalling 3 (SOCS3) in biopsy specimens from patients with ulcerative colitis (UC) and UC-related colorectal cancer (CRC) progression. Methods Biopsy specimens from patients with inactive UC (n=18), active UC (n=28), UC with low-grade dysplasia (LGD) (n=9), UC with high-grade dysplasia (HGD) (n=7), UC-CRC (n=11) and sporadic CRC (n=14) were included. Biopsy specimens (n=9) from patients without colonic abnormalities served as control. The protein expression of IL6, p-STAT3 and SOCS3 was determined immunohistochemically. Results Patients with active UC had significantly more IL6 and p-STAT3-positive epithelial cells than both patients with inactive UC and controls (strong positive IL6: 53.6%, 11.1% and 0%, respectively; p-STAT3: 64.3%, 22.2% and 11.1%, respectively; all p≤0.012). SOCS3-positive cells were significantly increased in colonic epithelium of both inactive and active UC compared with controls (strong positive: 94.4%, 96.4% and 11.1%, respectively; both pConclusion The importance of IL6/p-STAT3 in patients with inflammation-induced CRC was demonstrated. Moreover, SOCS3 may be involved in UC pathogenesis and the absence of SOCS3 seems critical for CRC progression.Keywords
This publication has 37 references indexed in Scilit:
- Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel diseaseInflammatory Bowel Diseases, 2008
- Interleukin-6 trans-signaling in inflammatory bowel diseaseCytokine & Growth Factor Reviews, 2006
- STAT3 activation via interleukin 6 trans-signalling contributes to ileitis in SAMP1/Yit miceGut, 2006
- Mechanisms of Disease: pathogenesis of Crohn's disease and ulcerative colitisNature Clinical Practice Gastroenterology & Hepatology, 2006
- Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancerJournal of Leukocyte Biology, 2006
- Negative regulation of cytokine signaling and immune responses by SOCS proteinsArthritis Research & Therapy, 2005
- TheRole ofSuppressors ofCytokineSignaling(SOCS) Proteins inRegulation of theImmuneResponseAnnual Review of Immunology, 2004
- Suppressors of cytokine signaling and immunityNature Immunology, 2003
- The risk of colorectal cancer in ulcerative colitis: a meta-analysisGut, 2001
- Colonic Mucosal Interleukin-6 in Inflammatory Bowel DiseaseDigestion, 1991