title: Intestinal alkaline phosphatase has beneficial effects in mouse models of chronic colitis.
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.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Sundaram
authors.initials: S
authors.lastname: Ramasamy
authors.forename: Deanna D
authors.initials: DD
authors.lastname: Nguyen
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Eston
authors.forename: Sayeda Nasrin
authors.initials: SN
authors.lastname: Alam
authors.forename: Angela K
authors.initials: AK
authors.lastname: Moss
authors.forename: Farzad
authors.initials: F
authors.lastname: Ebrahimi
authors.forename: Brishti
authors.initials: B
authors.lastname: Biswas
authors.forename: Golam
authors.initials: G
authors.lastname: Mostafa
authors.forename: Kathryn T
authors.initials: KT
authors.lastname: Chen
authors.forename: Kanakaraju
authors.initials: K
authors.lastname: Kaliannan
authors.forename: Halim
authors.initials: H
authors.lastname: Yammine
authors.forename: Sonoko
authors.initials: S
authors.lastname: Narisawa
authors.forename: José Luis
authors.initials: JL
authors.lastname: Millán
authors.forename: H Shaw
authors.initials: HS
authors.lastname: Warren
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Hohmann
authors.forename: Emiko
authors.initials: E
authors.lastname: Mizoguchi
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Reinecker
authors.forename: Atul K
authors.initials: AK
authors.lastname: Bhan
authors.forename: Scott B
authors.initials: SB
authors.lastname: Snapper
authors.forename: Madhu S
authors.initials: MS
authors.lastname: Malo
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hodin
mesh_terms: D000469:Alkaline Phosphatase / Q000008:administration & dosage*; D000818:Animals; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D014923:Wiskott-Aldrich Syndrome; D051316:Wiskott-Aldrich Syndrome Protein / Q000502:physiology
chemical_list: D016207:Cytokines; D051316:Wiskott-Aldrich Syndrome Protein; D016264:Dextran Sulfate; D009195:Peroxidase; D000469:Alkaline Phosphatase