Intestinal alkaline phosphatase has beneficial effects in mouse models of chronic colitis.
Intestinal alkaline phosphatase has beneficial effects in mouse models of chronic colitis.
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DOI：
10.1002/ibd.21377
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发表时间：
2011-02
影响因子：
4.9
通讯作者：
Hodin, Richard A.
中科院分区：
文献类型：
--
作者：
Ramasamy, Sundaram;Nguyen, Deanna D.;Eston, Michelle A.;Alam, Sayeda Nasrin;Moss, Angela K.;Ebrahimi, Farzad;Biswas, Brishti;Mostafa, Golam;Chen, Kathryn T.;Kaliannan, Kanakaraju;Yammine, Halim;Narisawa, Sonoko;Millan, Jose Luis;Warren, H. Shaw;Hohmann, Elizabeth L.;Mizoguchi, Emiko;Reinecker, Hans-Christian;Bhan, Atul K.;Snapper, Scott B.;Malo, Madhu S.;Hodin, Richard A.
关键词：
刷边酶肠碱性磷酸酶（IAP）作为一种肠道黏膜防御因子，对大鼠葡聚糖硫酸钠（DSS）急性损伤具有保护作用。本研究评估了口服小牛IAP （cIAP）在两种独立的慢性结肠炎小鼠模型中的潜在治疗作用：(1)dss诱导的慢性结肠炎，(2)照射加速的Wiskott-Aldrich综合征蛋白（WASP）缺陷（敲除）小鼠的慢性自发性结肠炎。野生型（WT）和IAP敲除型（IAP- ko）小鼠接受4个周期的2% DSS，持续7天。每个周期之后是7天的无dss间隔，在此期间小鼠在饮用水中接受cIAP或车辆。从照射当天开始，WASP-KO小鼠分别接受载药或cIAP治疗，为期6周。dss处理的IAP-KO小鼠结肠炎显微评分高于dss处理的WT小鼠（分别为52±3.8比28.8±6.6,P < 0.0001）。两组患者经cIAP治疗后病情均有所减轻（KO = 30.7±6.01,WT = 18.7±5.0,P < 0.05）。与对照组相比，辐照后的WASP-KO小鼠cIAP也能减轻结肠炎（分别为3.3±0.52比6.2±0.34,P < 0.001）。cIAP治疗后，组织髓过氧化物酶活性和促炎细胞因子显著降低。内源性IAP似乎在保护宿主免受慢性结肠炎方面发挥作用。口服cIAP在两种独立的慢性结肠炎小鼠模型中发挥保护作用，可能代表一种治疗人类IBD的新方法。
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. The wild-type (WT) and IAP knockout (IAP-KO) mice received 4 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. Microscopic colitis scores of DSS-treated IAP-KO mice were higher than DSS-treated WT mice (52 ± 3.8 vs. 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 vs. 6.2 ± 0.34, respectively, P < 0.001). Tissue myeloperoxidase activity and pro-inflammatory cytokines were significantly decreased by cIAP treatment. 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.
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影响因子：
20.3
作者：
Klein, C;Nguyen, D;Snapper, SB
通讯作者：
Snapper, SB
DOI：
10.1083/jcb.200902147
发表时间：
2009-06-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
McConnell RE;Higginbotham JN;Shifrin DA Jr;Tabb DL;Coffey RJ;Tyska MJ
通讯作者：
Tyska MJ
影响因子：
2.6
作者：
Hudcovic, T;Stepánková, R;Tlaskalová-Hogenová, H
通讯作者：
Tlaskalová-Hogenová, H
影响因子：
8.6
作者：
Adriani, Marsilio;Aoki, Joseph;Schwartzberg, Pamela L.
通讯作者：
Schwartzberg, Pamela L.
影响因子：
20.3
作者：
Bouma, Gerben;Burns, Siobhan;Thrasher, Adrian J.
通讯作者：
Thrasher, Adrian J.