Format

Send to

Choose Destination
Inflamm Bowel Dis. 2009 Oct;15(10):1515-25. doi: 10.1002/ibd.20951.

Role of TNF receptors, TNFR1 and TNFR2, in dextran sodium sulfate-induced colitis.

Author information

1
Department of Microbiology and Immunology, Dalhousie University, IWK Health Centre, Halifax, Nova Scotia, Canada.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
19479745
DOI:
10.1002/ibd.20951
[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center