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Keywords:

  • tumor necrosis factor;
  • TNFR1;
  • TNFR2;
  • colitis;
  • knockout mouse

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. Inflamm Bowel Dis 2009