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P017. The effect of intestinal alkaline phosphatase on intestinal epithelial cells, macrophages and chronic colitis in interleukin-10-deficient mice

C. Lee1, J. Chun2, S.W. Hwang2, S.J. Kang1, J.P. Im2, J.S. Kim2, 1Healthcare sytem, Gangnamcenter, Seoul national university hospital, Internal medicine, Seoul, Korea, Republic of, 2Seoul National University College of Medicine, Department of Internal Medicine and Liver Research Institute, Seoul, Korea, Republic of

Background

Intestinal alkaline phosphatase (IAP) is an intestinal brush border enzyme that has been shown to function as a gut mucosal defense factor, but its defensive mechanism remains unclear. The aims of this study were to evaluate the effect of IAP on intestinal epithelial cells and macrophages, and on chronic colitis in interleukin-10-deficient (IL-10−/−) mice.

Methods

Human intestinal epithelial cells COLO 205 and peritoneal macrophages from IL-10−/− mice were pretreated with IAP and then stimulated with lipopolysaccharide (LPS). IL-8 secretion from COLO 205 cells and TNF-α, IL-6, IL-12 from peritoneal macrophages were measured by ELISA. Electrophoretic mobility shift assay to assess the DNA binding activity of NF-κB and immunoblotting assay was used to assess IκBα phosphorylation/degradation in COLO 205. For the in vivo study, colitis was induced in IL-10−/− mice with piroxicam, the mice were treated with 100 or 300 units of IAP by oral gavage for 2 weeks. Colitis was quantified by histologic scoring, and the phosphorylation of IκBα in the colonic mucosa was assessed using immunohistochemistry.

Results

IAP significantly inhibited LPS-induced inflammatory cytokine production in both IECs and peritoneal macrophages. IAP also attenuated LPS-induced NF-κB binding activity and IκBα phosphorylation/degradation in IECs. Oral administration of IAP significantly reduced the severity of colitis and down-regulated colitis-induced IκBα phosphorylation in IL-10−/− mice.

Conclusion

IAP may inhibit activation of intestinal epithelial cells and peritoneal macrophages, and attenuates chronic murine colitis. This finding suggests that IAP supplementation is a potential therapeutic option for inflammatory bowel disease.