title: Proximal gut mucosal epithelial homeostasis in aged IL-1 type I receptor knockout mice after starvation.
abstract: BACKGROUND
  Previous studies have shown that starvation induces small bowel atrophy, and that atrophy diminishes with aging. In this experiment, we assessed whether starvation-induced atrophy of proximal gut mucosa is associated with the Interleukin-1 receptor (IL-1R) signaling pathway in aged mice.
  
  
  METHODS
  Thirty 26-month-old IL-1R knockout mice and age-matched wild-type C57BL/6 mice were randomly divided into two groups: ad libitum fed and fasted. Mice were euthanized 12 or 48 hours after starvation. The proximal small bowel was harvested for morphologic analysis. Gut epithelial cell proliferation was detected using immunohistochemical staining for proliferating cell nuclear antigen (PCNA), and apoptosis was identified using terminal deoxyuridine nick-end labeling (TUNEL) staining.
  
  
  RESULTS
  Aged IL-1R knockout mice were larger than aged-matched wild-type mice (P < 0.05). Proximal gut mucosal height and mucosal cell number were not different between aged IL-1R knockout and wild-type groups. The apoptosis index in gut epithelial cells was higher in fed IL-1R knockout versus wild-type mice (P < 0.05), while there was no significant difference in cell proliferation between both groups. Mucosal atrophy was induced in both aged IL-1R knockout and wild-type groups by starvation (P < 0.05), however, aged IL-1R knockout mice experienced greater loss in proximal gut weight, mucosal length, and corresponding cell number than did wild-type mice at the 12-h time point (P < 0.05). The apoptosis index in gut epithelial cells significantly increased in both groups after starvation (P < 0.05). Starvation decreased cell proliferation in IL-1R knockout mice (P < 0.05), but not in wild-type mice.
  
  
  CONCLUSIONS
  The response in aged IL-1R knockout mice differs from wild-type mice in that starvation increases atrophy and is associated with decreased cell proliferation rather than increased apoptosis.
authors.affiliation: Shriners Hospitals for Children, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Juquan
authors.initials: J
authors.lastname: Song
authors.forename: Steven E
authors.initials: SE
authors.lastname: Wolf
authors.forename: Xiao-Wu
authors.initials: XW
authors.lastname: Wu
authors.forename: Celeste C
authors.initials: CC
authors.lastname: Finnerty
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Marc G
authors.initials: MG
authors.lastname: Jeschke
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001284:Atrophy / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000473:pathology* / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D007413:Intestinal Mucosa / Q000473:pathology* / Q000503:physiopathology; D007421:Intestine, Small / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D017472:Receptors, Interleukin-1 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013217:Starvation / Q000473:pathology* / Q000503:physiopathology
chemical_list: D017472:Receptors, Interleukin-1