Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells.
Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells.
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DOI：
10.1371/journal.pone.0074010
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dartt DA
中科院分区：
文献类型：
--
作者：
McGilligan VE;Gregory-Ksander MS;Li D;Moore JE;Hodges RR;Gilmore MS;Moore TC;Dartt DA
结膜是一层湿润的粘膜，它经常暴露在一系列潜在的病原体和炎症诱因中。NACHT、leucine rich repeat （LRR）和pyrin domain containing protein 3 （NLRP3）是一种能感知病原体或其他触发因素的nod样受体，在湿粘膜中高度表达。NLRP3是被称为NLRP3炎性体的多蛋白复合物的一员，它激活caspase 1通路，诱导分泌具有生物活性的IL-1β， IL-1β是炎症的主要发起者和促进者。本研究的目的是：(1)确定NLRP3是否在结膜中表达；(2)确定杯状细胞是否通过分泌IL-1β特异性地参与先天介导的炎症。我们报道了已知参与NLRP3炎症小体的启动和激活的受体，嘌呤能受体P2X4和P2X7以及细菌toll样受体2在结膜杯状细胞中存在并起作用。含毒素的金黄色葡萄球菌（S. aureus）激活NLRP3炎性小体，增加了结膜杯状细胞中炎性小体蛋白NLRP3、ASC和前、成熟caspase 1的表达。在金黄色葡萄球菌作用下的杯状细胞培养上清中检测到IL-1β的生物活性形式，当细胞用caspase 1抑制剂Z-YVAD处理时，IL-1β的生物活性降低。我们得出结论，NLRP3炎性体成分存在于结膜杯状细胞中。含有毒素的金黄色葡萄球菌通过caspase 1途径激活结膜杯状细胞中的NRLP3炎性小体，分泌成熟的il - 1-β。因此杯状细胞通过激活NLRP3炎性体参与结膜的先天免疫反应。
The conjunctiva is a moist mucosal membrane that is constantly exposed to an array of potential pathogens and triggers of inflammation. The NACHT, leucine rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3) is a Nod-like receptor that can sense pathogens or other triggers, and is highly expressed in wet mucosal membranes. NLRP3 is a member of the multi-protein complex termed the NLRP3 inflammasome that activates the caspase 1 pathway, inducing the secretion of biologically active IL-1β, a major initiator and promoter of inflammation. The purpose of this study was to: (1) determine whether NLRP3 is expressed in the conjunctiva and (2) determine whether goblet cells specifically contribute to innate mediated inflammation via secretion of IL-1β. We report that the receptors known to be involved in the priming and activation of the NLRP3 inflammasome, the purinergic receptors P2X4 and P2X7 and the bacterial Toll-like receptor 2 are present and functional in conjunctival goblet cells. Toxin-containing Staphylococcus aureus (S. aureus), which activates the NLRP3 inflammasome, increased the expression of the inflammasome proteins NLRP3, ASC and pro- and mature caspase 1 in conjunctival goblet cells. The biologically active form of IL-1β was detected in goblet cell culture supernatants in response to S. aureus, which was reduced when the cells were treated with the caspase 1 inhibitor Z-YVAD. We conclude that the NLRP3 inflammasome components are present in conjunctival goblet cells. The NRLP3 inflammasome appears to be activated in conjunctival goblet cells by toxin-containing S. aureus via the caspase 1 pathway to secrete mature IL1-β. Thus goblet cells contribute to the innate immune response in the conjunctiva by activation of the NLRP3 inflammasome.
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DOI：
10.1038/nri2851
发表时间：
2010-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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DOI：
10.1074/jbc.m110.203398
发表时间：
2011-08-05
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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通讯作者：
Rubartelli A
影响因子：
2.8
作者：
Keller, Jean-Francois;Carrouel, Florence;Farges, Jean-Christophe
通讯作者：
Farges, Jean-Christophe
影响因子：
5.2
作者：
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通讯作者：
Gilmore, Michael S.
影响因子：
30.5
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