Regulation of NOD-like receptors and inflammasome activation in cerebral endothelial cells

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-asso...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Nagyőszi Péter
Nyúl-Tóth Ádám
Fazakas Csilla
Wilhelm Imola Mária
Kozma Mihály
Molnár Judit
Haskó János
Krizbai István Adorján
Dokumentumtípus: Cikk
Megjelent: Wiley-Blackwell Publishing Ltd. 2015
Sorozat:JOURNAL OF NEUROCHEMISTRY 135 No. 3
doi:10.1111/jnc.13197

mtmt:2938595
Online Access:http://publicatio.bibl.u-szeged.hu/8804
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520 3 |a 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-gamma, tumor necrosis factor-alpha, and IL-1beta 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-1beta 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-1beta 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. Here, we show that cerebral endothelial cells (CECs), the main components of the blood-brain barrier, express several NOD (nucleotide-binding oligomerization domain-containing protein)-like receptors and are able to assemble functional inflammasomes. Expression of key inflammasome components (NOD2, NLRP3, and caspase 1) along with caspase-cleaved interleukins IL-1beta and IL-33 can be induced in CECs by priming with lipopolysaccharide (LPS) and activation with muramyl dipeptide (MDP). Combined treatment with LPS and MDP results in IL-1beta secretion in a caspase (i.e., inflammasome)- and ERK1/2-dependent manner. 
700 0 2 |a Nyúl-Tóth Ádám  |e aut 
700 0 2 |a Fazakas Csilla  |e aut 
700 0 2 |a Wilhelm Imola Mária  |e aut 
700 0 2 |a Kozma Mihály  |e aut 
700 0 2 |a Molnár Judit  |e aut 
700 0 2 |a Haskó János  |e aut 
700 0 2 |a Krizbai István Adorján  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/8804/1/2015_Nagyoszi_Nyul_Toth_J_Neurochem_NOD_u.pdf  |z Dokumentum-elérés  
856 4 0 |u http://publicatio.bibl.u-szeged.hu/8804/2/jnc_13197_corrected.pdf  |z Dokumentum-elérés