The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis.
The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis.
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DOI：
10.1016/j.immuni.2010.03.003
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发表时间：
2010-03-26
期刊：
影响因子：
32.4
通讯作者：
Kanneganti TD
中科院分区：
文献类型：
--
作者：
Zaki MH;Boyd KL;Vogel P;Kastan MB;Lamkanfi M;Kanneganti TD
克罗恩病和溃疡性结肠炎是人类中发病率较高的炎症性肠病。Nlrp 3与衔接蛋白ASC相互作用以激活炎性体中的半胱天冬酶-1，炎性体是负责IL-1β和IL-18的成熟和分泌的蛋白质复合物。NOD样受体（NLR）Nlrp 3的表达减少最近与克罗恩病的易感性有关。然而，Nlrp 3在结肠炎中的作用尚未被表征。在这里，我们表明，小鼠缺乏Nlrp 3或炎症体效应ASC和caspase-1是非常敏感的葡聚糖硫酸钠（DSS）诱导的结肠炎。炎性小体活化缺陷导致上皮完整性丧失，导致结肠细菌的全身分散、大量白细胞浸润和结肠中趋化因子产生增加。因此，对于缺乏Nlrp 3炎性体组分的小鼠，注意到显著更高的死亡率。因此，Nlrp 3炎性体关键地参与维持肠内稳态和防止结肠炎。
Crohn’s disease and ulcerative colitis are inflammatory bowel diseases with high prevalence in humans. Nlrp3 interacts with the adaptor protein ASC to activate caspase-1 in inflammasomes, protein complexes responsible for the maturation and secretion of IL-1β and IL-18. Decreased expression of the NOD-like receptor (NLR) Nlrp3 was recently associated with susceptibility to Crohn’s disease. However, the role of Nlrp3 in colitis has not been characterized. Here, we show that mice deficient for Nlrp3 or the inflammasome effectors ASC and caspase-1 are highly susceptible to dextran sodium sulfate (DSS)-induced colitis. Defective inflammasome activation leads to loss of epithelial integrity, resulting in systemic dispersion of commensal bacteria, massive leukocyte infiltration and increased chemokine production in the colon. As a consequence, significantly higher mortality rates were noted for mice lacking components of the Nlrp3 inflammasome. Therefore, the Nlrp3 inflammasome is critically involved in the maintenance of intestinal homeostasis and protection against colitis.
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DOI：
10.1152/ajpgi.00328.2004
发表时间：
2005-05-01
影响因子：
4.5
作者：
Fukata, M;Michelsen, KS;Abreu, MT
通讯作者：
Abreu, MT
影响因子：
15.9
作者：
Horwood, NJ;Udagawa, N;Gillespie, MT
通讯作者：
Gillespie, MT
影响因子：
3.2
作者：
Kummer, J. Alain;Broekhuizen, Roel;Tschopp, Juerg
通讯作者：
Tschopp, Juerg
影响因子：
32.4
作者：
Agostini, L;Martinon, F;Tschopp, J
通讯作者：
Tschopp, J
DOI：
10.1084/jem.193.9.1027
发表时间：
2001-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Furuta GT;Turner JR;Taylor CT;Hershberg RM;Comerford K;Narravula S;Podolsky DK;Colgan SP
通讯作者：
Colgan SP