title: Increased small bowel epithelial turnover in interleukin-1 receptor knockout mice.
abstract: OBJECTIVE
  To determine whether interleukin-1 (IL-1) affects the cellular homeostasis of small bowel mucosa, the authors studied apoptosis and proliferation in small bowel epithelium in two groups of C57 mice: an IL-1 receptor knockout group, and a control wild-type group.
  
  
  BACKGROUND
  Gut mucosal integrity is maintained by a balance of cell proliferation and cell death. Recent reports suggest that IL-1, a proinflammatory cytokine, increases cell death by apoptosis in some epithelial cells.
  
  
  METHODS
  Twenty-four male C57BL6 IL-1 receptor (type I) knockout mice were killed, and small bowel was removed for study. Twenty-four wild-type mice (C57-BL6) served as controls. Body weights, bowel length, and mucosal morphology were examined for phenotypic differences. Apoptosis was quantified by terminal deoxyuridine nick-end labeling (TUNEL) immunohistochemical staining and cellular proliferation by proliferation cell nuclear antigen staining. Whole mucosal protein was analyzed for nuclear factor-kappaB expression. Groups were analyzed by t test.
  
  
  RESULTS
  The absence of IL-1 type I receptor in knockout mice was verified by reverse transcriptase-polymerase chain reaction. IL-1 receptor null mice were larger than wild-type controls, with a longer small bowel; however, the index of small bowel length to total body weight did not differ between groups. The percentage of apoptotic cells was higher in IL-1 receptor null mice than in wild-type mice; the proliferation index also increased. Mucosal height and other measures of mucosal morphology were not different. Genotypic absence of IL-1 receptors was associated with decreased expression of nuclear factor-kappaB in whole mucosal protein extracts.
  
  
  CONCLUSIONS
  Both apoptosis and proliferation increased in gut epithelial cells 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.
authors.affiliation: Department of Surgery, The University of Texas Medical Branch and The Shriners Hospitals for Children, Galveston, Texas, USA. swolf@sbi.utmb.edu
authors.forename: S E
authors.initials: SE
authors.lastname: Wolf
authors.forename: M A
authors.initials: MA
authors.lastname: Debroy
authors.forename: H
authors.initials: H
authors.lastname: Ikeda
authors.forename: M
authors.initials: M
authors.lastname: Jeschke
authors.forename: S
authors.initials: S
authors.lastname: Matin
authors.forename: S
authors.initials: S
authors.lastname: Rajaraman
authors.forename: T C
authors.initials: TC
authors.lastname: Ko
authors.forename: E W
authors.initials: EW
authors.lastname: Englander
authors.forename: J G
authors.initials: JG
authors.lastname: Norman
authors.forename: J C
authors.initials: JC
authors.lastname: Thompson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002455:Cell Division; D006706:Homeostasis / Q000502:physiology; D020287:In Situ Nick-End Labeling; D007375:Interleukin-1 / Q000502:physiology*; D007413:Intestinal Mucosa / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D007375:Interleukin-1