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

✍ Scribed by RoseMarie Stillie; Andrew W. Stadnyk

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 439 KB
• Volume: 15
• Category: Article
• ISSN: 1078-0998
• DOI: 10.1002/ibd.20951

✦ Synopsis

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.