Intestinal alkaline phosphatase has beneficial effects in mouse models of chronic colitis

Sundaram Ramasamy, Deanna D. Nguyen, Michelle A. Eston, Sayeda Nasrin Alam, Angela K. Moss, Farzad Ebrahimi, Brishti Biswas, Golam Mostafa, Kathryn T. Chen, Kanakaraju Kaliannan, Halim Yammine, Sonoko Narisawa, José Luis Millán, H. Shaw Warren, Elizabeth L. Hohmann, Emiko Mizoguchi, Hans Christian Reinecker, Atul K. Bhan, Scott B. Snapper, Madhu S. MaloRichard A. Hodin

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Background: The brush border enzyme intestinal alkaline phosphatase (IAP) functions as a gut mucosal defense factor and is protective against dextran sulfate sodium (DSS)-induced acute injury in rats. The present study evaluated the potential therapeutic role for orally administered calf IAP (cIAP) in two independent mouse models of chronic colitis: 1) DSS-induced chronic colitis, and 2) chronic spontaneous colitis in Wiskott-Aldrich Syndrome protein (WASP)-deficient (knockout) mice that is accelerated by irradiation. Methods: The wildtype (WT) and IAP knockout (IAP-KO) mice received four cycles of 2% DSS ad libitum for 7 days. Each cycle was followed by a 7-day DSS-free interval during which mice received either cIAP or vehicle in the drinking water. The WASP-KO mice received either vehicle or cIAP for 6 weeks beginning on the day of irradiation. Results: Microscopic colitis scores of DSS-treated IAP-KO mice were higher than DSS-treated WT mice (52 ± 3.8 versus 28.8 ± 6.6, respectively, P < 0.0001). cIAP treatment attenuated the disease in both groups (KO = 30.7 ± 6.01, WT = 18.7 ± 5.0, P < 0.05). In irradiated WASP-KO mice cIAP also attenuated colitis compared to control groups (3.3 ± 0.52 versus 6.2 ± 0.34, respectively, P < 0.001). Tissue myeloperoxidase activity and proinflammatory cytokines were significantly decreased by cIAP treatment. Conclusions: Endogenous IAP appears to play a role in protecting the host against chronic colitis. Orally administered cIAP exerts a protective effect in two independent mouse models of chronic colitis and may represent a novel therapy for human IBD. (Inflamm Bowel Dis 2011)

Original languageEnglish (US)
Pages (from-to)532-542
Number of pages11
JournalInflammatory bowel diseases
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

Keywords

  • DSS-induced chronic colitis
  • gut mucosal defense
  • inflammatory bowel disease
  • lipopolysaccharides
  • spontaneous chronic colitis
  • WASP-KO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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  • Cite this

    Ramasamy, S., Nguyen, D. D., Eston, M. A., Nasrin Alam, S., Moss, A. K., Ebrahimi, F., Biswas, B., Mostafa, G., Chen, K. T., Kaliannan, K., Yammine, H., Narisawa, S., Millán, J. L., Warren, H. S., Hohmann, E. L., Mizoguchi, E., Reinecker, H. C., Bhan, A. K., Snapper, S. B., ... Hodin, R. A. (2011). Intestinal alkaline phosphatase has beneficial effects in mouse models of chronic colitis. Inflammatory bowel diseases, 17(2), 532-542. https://doi.org/10.1002/ibd.21377