Regulation of NOD-like receptors and inflammasome activation in cerebral endothelial cells
Regulation of NOD-like receptors and inflammasome activation in cerebral endothelial cells
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DOI：
10.1111/jnc.13197
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发表时间：
2015-11-01
影响因子：
4.7
通讯作者：
Krizbai, Istvan A.
中科院分区：
文献类型：
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作者：
Nagyoszi, Peter;Nyul-Toth, Adam;Krizbai, Istvan A.
脑内皮细胞（cerebral endothelial cells，CEC）是免疫系统和中枢神经系统的界面细胞，在免疫系统和中枢神经系统的功能整合中发挥重要作用。在这里，我们研究了CEC如何识别和响应病原体和损伤相关的分子模式，以调节神经血管单位的功能。首先，我们检测了几种NOD样受体（NLR）-包括NOD 1，NOD 2，NLRC 4，NLRC 5，NLRP 1，NLRP 3，NLRP 5，NLRP 9，NLRP 10，NLRP 12，NLRA和NLRX -在人脑内皮细胞中的表达。炎性细胞因子，如干扰素，肿瘤坏死因子，和IL-1对许多这些受体的转录有刺激作用。关键炎性体组分（NOD 2、NLRP 3和半胱天冬酶1）沿着半胱天冬酶裂解的白细胞介素IL-1和IL-33的表达可以通过脂多糖引发和胞壁酰二肽活化来诱导。此外，与脂多糖和胞壁酰二肽的组合治疗导致IL-1的分泌在半胱天冬酶和ERK 1/2激酶依赖的方式。我们的研究结果表明，NLR和炎性小体可以在脑内皮细胞中被激活，这可能赋予血脑屏障在神经免疫和神经炎症过程中尚未探索的作用。
Cerebral endothelial cells (CECs) forming the blood-brain barrier are at the interface of the immune and the central nervous systems and thus may play an important role in the functional integration of the two systems. Here, we investigated how CECs recognize and respond to pathogen- and damage-associated molecular patterns to regulate the functions of the neurovascular unit. First we detected the expression of several NOD-like receptors (NLRs) - including NOD1, NOD2, NLRC4, NLRC5, NLRP1, NLRP3, NLRP5, NLRP9, NLRP10, NLRP12, NLRA, and NLRX - in human brain endothelial cells. Inflammatory cytokines, such as interferon-, tumor necrosis factor-, and IL-1 had stimulatory effects on the transcription of many of these receptors. Expression of key inflammasome components (NOD2, NLRP3, and caspase 1) along with caspase-cleaved interleukins IL-1 and IL-33 could be induced by priming with lipopolysaccharide and activation with muramyl dipeptide. In addition, combined treatment with lipopolysaccharide and muramyl dipeptide resulted in IL-1 secretion in a caspase- and ERK1/2 kinase-dependent manner. Our findings demonstrate that NLRs and inflammasomes can be activated in cerebral endothelial cells, which may confer a yet unexplored role to the blood-brain barrier in neuroimmune and neuroinflammatory processes.