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

• Published in: Inflammatory bowel diseases 2009-10, Vol.15 (10), p.1515-1525
• Main Authors: Stillie, RoseMarie, Stadnyk, Andrew W.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Blotting, Western; Caspase Inhibitors; Caspases - metabolism; colitis; Colitis - chemically induced; Colitis - metabolism; Colitis - pathology; Colon - drug effects; Colon - metabolism; Dextran Sulfate - toxicity; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Eosinophils - immunology; Eosinophils - metabolism; Eosinophils - pathology; Female; Immunoenzyme Techniques; In Situ Nick-End Labeling; knockout mouse; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils - immunology; Neutrophils - metabolism; Neutrophils - pathology; Receptors, Tumor Necrosis Factor, Type I - physiology; Receptors, Tumor Necrosis Factor, Type II - physiology; TNFR1; TNFR2; tumor necrosis factor
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1002/ibd.20951

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