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Mice deficient in receptors for TNF‐α and IL‐1 are not protected against DSS‐induced colitis
Author(s) -
Stillie RoseMarie,
Stadnyk Andrew W
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb124
Subject(s) - colitis , tumor necrosis factor alpha , medicine , tunel assay , receptor , apoptosis , immunology , tumor necrosis factor receptor 1 , gastroenterology , biology , immunohistochemistry , tumor necrosis factor receptor , biochemistry
Tumor necrosis factor (TNF)‐α and interleukin (IL)‐1 are involved in the pathogenesis of T‐cell‐independent dextran sulphate sodium (DSS)‐ induced colitis, however, their roles are unclear. The objective of this study was to determine the severity of colitis in mice lacking the TNFR1, TNFR2, or the IL‐1RI compared to wildtype mice. Mice (C57Bl/6, TNFR1 −/− , TNFR2 −/− , and IL‐1RI −/− ) were fed 3% w/v DSS through drinking water for 5 days then were killed 2 days later to evaluate acute colitis. DSS feeding resulted in no significant differences in weight loss between C57Bl/6, TNFR1 −/− and IL‐1RI −/− (9.4%±1.9%), however, TNFR2 −/− mice lost significantly more weight compared to other strains (18%±3.4%). Occult stool blood appeared on day 2 of DSS feeding in TNFR2 −/− mice but on day 3 of DSS feeding in the other strains. Therefore, TNFR2 −/− mice, determined by weight loss and occult blood, appeared to develop the most severe colitis. Mice fed DSS had shorter colons compared to their respective non‐DSS treated controls, and TNFR1 −/− and IL‐1RI −/− mice had significantly shorter colons than inflamed C57Bl/6 mice. Clinical and histopathological scores were similar between strains fed DSS. Colonic epithelial apoptosis, determined by TUNEL, was similar between strains fed DSS. These data suggest that there is redundancy in the roles of TNF‐α and IL‐1 receptors in DSS colitis. Funded by Dalhousie Cancer Research Program and Nova Scotia Health Research Foundation