title: Regulation of NOD-like receptors and inflammasome activation in cerebral endothelial cells.
abstract: 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-γ, tumor necrosis factor-α, and IL-1β 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-1β 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-1β 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.
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Nagyőszi
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Nyúl-Tóth
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Csilla
authors.initials: C
authors.lastname: Fazakas
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Imola
authors.initials: I
authors.lastname: Wilhelm
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Mihály
authors.initials: M
authors.lastname: Kozma
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Molnár
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Haskó
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: István A
authors.initials: IA
authors.lastname: Krizbai
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053474:Nod1 Signaling Adaptor Protein / Q000502:physiology*; D053473:Nod2 Signaling Adaptor Protein / Q000502:physiology*; D051381:Rats
chemical_list: D058847:Inflammasomes; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein
keywords: IL-1β; NOD-like receptors; blood-brain barrier; cerebral endothelial cells; inflammasome