Increased small bowel epithelial turnover in interleukin-1 receptor knockout mice

Objective To determine whether interleukin-1 (IL-1) affects the cellular ho meostasis of small bowel mucosa, the authors studied apoptosis and prolifer ation in small bowel epithelium in two groups of C57 mice: an IL-1 receptor knockout group, and a control wild-type group. Summary Background Data Gut mucosal integrity is maintained by a balance of cell proliferation and cell death. Recent reports suggest that IL-1, a pro inflammatory cytokine, increases cell death by apoptosis in some epithelial cells. Methods Twenty-four male C57BL6 IL-1 receptor(type I) knockout mice were ki lled, and small bowel was removed for study. Twenty-four wild-type mice (C5 7-BL6) served as controls. Body weights, bowel length, and mucosal morpholo gy were examined for phenotypic differences. Apoptosis was quanti fled by t erminal deoxyuridine nick-end labeling (TUNEL) immunohistochemical staining and cellular proliferation by proliferation cell nuclear antigen staining. Whole mucosal protein was analyzed for nuclear factor-kappa B expression. Groups were analyzed by t test. Results The absence of IL-1 type I receptor in knockout mice was verified b y reverse transcriptase-polymerase chain reaction. IL-1 receptor null mice were larger than wild-type controls, with a longer small bowel; however, th e index of small bowel length to total body weight did not differ between g roups, The percentage of apoptotic cells was higher in IL-1 receptor null m ice than in wild-type mice; the proliferation index also increased. Mucosal height and other measures of mucosal morphology were not different. Genoty pic absence of IL-1 receptors was associated with decreased expression of n uclear factor-kappa B in whole mucosal protein extracts. Conclusions Both apoptosis and proliferation increased in gut epithelial ce lls of mice without IL-1 receptors, suggesting increased cell turnover with no change in net balance. This model represents an opportunity to examine potential mechanisms of gut epithelial turnover in vivo, under both normal conditions and in conditions of mucosal proliferation and atrophy.