The effect of intestinal alkaline phosphatase on intestinal epithelial cells, macrophages and chronic colitis in mice

作者：Lee Changhyun; Chun Jaeyoung; Hwang Sung Wook; Kang Seung Joo; Im Jong Pil; Kim Joo Sung^*

来源：Life Sciences, 2014, 100(2): 118-124.

DOI：10.1016/j.lfs.2014.02.003

• Intestinal alkaline phosphatase
• Lipopolysaccharide
• IL-10 deficient mice
• Colitis
• Inflammatory bowel disease

Aims: Intestinal alkaline phosphatase (lAP) is an intestinal brush border enzyme that is 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 LAP on intestinal epithelial cells and macrophages, and on chronic colitis in interleukin-10-deficient (IL-10(-/-)) mice.
Main 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 COLO205 cells and TNF-alpha, IL-6, IL-12 from peritoneal macrophages were measured by EUSA. Electrophoretic mobility shift assay was used to assess the DNA binding activity of NF-kappa B and I kappa B alpha phosphorylation/degradation was evaluated by immunoblot assay in COW 205. For the in vivo study, colitis was induced in IL-10(-/-) mice with piroxicam, the mice were then treated with 100 or 300 units of LAP by oral gavage for 2 weeks. Colitis was quantified by histopathologic scoring, and the phosphorylation of Ma in the colonic mucosa was assessed using immunohistochemistry.
Key findings: IAP significantly inhibited LPS-induced inflammatory cytokine production in both IECs and peritoneal macrophages. IAP also attenuated LPS-induced NF-kappa B binding activity and I kappa B alpha phosphorylation/degradation in IECs. Oral administration of IAP significantly reduced the severity of colitis and down-regulated colitisinduced I kappa B alpha phosphorylation in IL-10(-/-) mice.
Significance: IAP may inhibit the activation of intestinal epithelial cells and peritoneal macrophages, and may attenuate chronic murine colitis. This finding suggests that IAP supplementation is a potential therapeutic option for inflammatory bowel disease.

• 出版日期2014-4-1