期刊
JOURNAL OF NEUROCHEMISTRY
卷 135, 期 3, 页码 551-564出版社
WILEY
DOI: 10.1111/jnc.13197
关键词
blood-brain barrier; cerebral endothelial cells; IL-1; inflammasome; NOD-like receptors
资金
- Hungarian Research Fund [OTKA PD-100958, K-100807]
- National Development Agency (Hungary-Romania Cross-Border Co-operation Programme) [HURO/1101/173/2.2.1, TAMOP-4.2.2.A-11/1/KONV-2012-0052]
- Hungarian Academy of Sciences [BO/00320/12/8]
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.
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