Proximal Gut Mucosal Epithelial Homeostasis in Aged IL-1 Type I Receptor Knockout Mice after Starvation

• Published in: The Journal of surgical research Vol. 169; no. 2; pp. 209 - 213
• Main Authors: Song, Juquan, M.D, Wolf, Steven E., M.D, Wu, Xiao-Wu, M.D, Finnerty, Celeste C., Ph.D, Herndon, David N., M.D, Jeschke, Marc G., M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-08-2011; Elsevier
• Subjects: Aging - pathology; Aging - physiology; Animals; apoptosis; Apoptosis - physiology; Atrophy - pathology; Atrophy - physiopathology; Biological and medical sciences; Cell Proliferation; Epithelial Cells - pathology; Epithelial Cells - physiology; General aspects; Homeostasis - physiology; Intestinal Mucosa - pathology; Intestinal Mucosa - physiopathology; Intestine, Small - pathology; Intestine, Small - physiopathology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Animal; PCNA staining; proliferation; Receptors, Interleukin-1 - deficiency; Receptors, Interleukin-1 - genetics; Receptors, Interleukin-1 - physiology; Signal Transduction - physiology; small intestinal epithelia; Starvation - pathology; Starvation - physiopathology; Surgery; TUNEL staining; small intestinal epithelia; apoptosis; PCNA staining; TUNEL staining; proliferation; Cell proliferation; Proximal; Starvation; Digestive system; Mucosa; Cytokine; Staining; Homeostasis; Epithelium; Small intestine; Famine; Treatment; Cell death; Animal; Interleukin 1; Knockout mouse; PCNA antigen; Apoptosis; Biological receptor
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2010.03.056

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. Materials and 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.