Intestinal Alkaline Phosphatase Has Beneficial Effects in Mouse Models of Chronic Colitis

被引：72

作者：

Ramasamy, Sundaram ^{[1
]}

Nguyen, Deanna D. ^{[2
,3
]}

Eston, Michelle A. ^{[2
,3
]}

Alam, Sayeda Nasrin ^{[1
]}

Moss, Angela K. ^{[1
]}

Ebrahimi, Farzad ^{[1
]}

Biswas, Brishti ^{[1
]}

Mostafa, Golam ^{[1
]}

Chen, Kathryn T. ^{[1
]}

Kaliannan, Kanakaraju ^{[1
]}

Yammine, Halim ^{[1
]}

Narisawa, Sonoko ^{[4
]}

Millan, Jose Luis ^{[4
]}

Warren, H. Shaw ^{[5
]}

Hohmann, Elizabeth L. ^{[6
]}

Mizoguchi, Emiko ^{[2
,3
]}

Reinecker, Hans-Christian ^{[2
,3
]}

Bhan, Atul K. ^{[3
,7
]}

Snapper, Scott B. ^{[2
,3
]}

Malo, Madhu S. ^{[1
]}

Hodin, Richard A. ^{[1
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, Boston, MA 02114 USA

[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA

[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA

[4] Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA USA

[5] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Infect Dis Unit, Boston, MA 02114 USA

[6] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Infect Dis Div, Boston, MA 02114 USA

[7] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA

来源：

INFLAMMATORY BOWEL DISEASES | 2011年 / 17卷 / 02期

基金：

美国国家卫生研究院;

关键词：

DSS-induced chronic colitis; WASP-KO; spontaneous chronic colitis; inflammatory bowel disease; gut mucosal defense; lipopolysaccharides; WISKOTT-ALDRICH-SYNDROME; INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS; SYNDROME PROTEIN; DEXTRAN SULFATE; MURINE DSS; IN-VITRO; MICE; WASP; DEFICIENT;

D O I：

10.1002/ibd.21377

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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 TAP 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.

引用

页码：532 / 542

页数：11

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