Role of TNF receptors, TNFR1 and TNFR2, in dextran sodium sulfate-induced colitis
Article first published online: 28 MAY 2009
Copyright © 2009 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 15, Issue 10, pages 1515–1525, October 2009
How to Cite
Stillie, R. and Stadnyk, A. W. (2009), Role of TNF receptors, TNFR1 and TNFR2, in dextran sodium sulfate-induced colitis. Inflamm Bowel Dis, 15: 1515–1525. doi: 10.1002/ibd.20951
- Issue published online: 11 SEP 2009
- Article first published online: 28 MAY 2009
- Manuscript Accepted: 1 MAR 2009
- Manuscript Received: 3 FEB 2009
- Crohn's and Colitis Foundation of Canada
- Cancer Research Training Program
- Nova Scotia Health Research Foundation
- Cancer Research Training Program at Dalhousie University
- tumor necrosis factor;
- knockout mouse
In this study we determined the consequence of the absence of each TNF receptor, TNFR1 or TNFR2, in the dextran sulfate sodium (DSS) model of colitis.
Wildtype (WT), TNFR1−/− and TNFR2−/− mice were fed 3% w/v DSS in drinking water for 5 days followed by 2 (day 7) or 7 (day 12) days of tap water.
The colons from untreated TNFR1−/− and TNFR2−/− mice were histologically normal. Following DSS, all strains became inflamed. TNFR1−/− mice had a more severe clinical score at days 8 and 9 compared to WT and TNFR2−/− mice despite similar histopathological damage in their colons. The more severe clinical score was associated with a reduced macrophage infiltration into the colonic mucosa. TNFR2−/− mice showed increased indicators of disease including increased colon weight, a shrunken cecum, and an increased number of ulcers compared to TNFR1−/− and WT strains at day 7. Mucosal levels of TNFR2 were elevated in colitic mice compared to uninflamed controls, with no difference between strains on day 7 but on day 12, unlike WT mice, levels were reduced in TNFR1−/− mice. There was no difference in the number of TUNEL-positive apoptotic colonic epithelial cells between strains, nor in total cleaved caspase 3 levels between strains, measured by Western blot of colon homogenates.
While deficiency of either receptor contributes to some measures of DSS colitis, the histopathological scores are similar, indicating that TNF receptors either do not play a major role or are redundant in the pathology associated with DSS colitis. Inflamm Bowel Dis 2009