Open AccessRole of nucleotide‐binding oligomerization domain 1 ( NOD 1) in pericyte‐mediated vascular inflammation
Author(s) -
Navarro Rocío,
DelgadoWicke Pablo,
NuñezPrado Natalia,
Compte Marta,
BlancoToribio Ana,
Nuñez Gabriel,
ÁlvarezVallina Luis,
Sanz Laura
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12804
Subject(s) - nod , nod1 , biology , receptor , microbiology and biotechnology , signal transduction , gene silencing , proinflammatory cytokine , inflammation , mapk/erk pathway , innate immune system , immunology , nod2 , biochemistry , gene
Abstract We have recently described the response of human brain pericytes to lipopolysaccharide ( LPS ) through toll‐like receptor 4 ( TLR 4). However, Gram‐negative pathogen‐associated molecular patterns include not only LPS but also peptidoglycan ( PGN ). Given that the presence of co‐purified PGN in the LPS preparation previously used could not be ruled out, we decided to analyse the expression of the intracellular PGN receptors NOD 1 and NOD 2 in HBP and compare the responses to their cognate agonists and ultrapure LPS . Our findings show for the first time that NOD 1 is expressed in pericytes, whereas NOD 2 expression is barely detectable. The NOD 1 agonist C12‐iE‐ DAP induced IL 6 and IL 8 gene expression by pericytes as well as release of cytokines into culture supernatant. Moreover, we demonstrated the synergistic effects of NOD 1 and TLR 4 agonists on the induction of IL 8 . Using NOD 1 silencing in HBP , we showed a requirement for C12‐iE‐ DAP ‐dependent signalling. Finally, we could discriminate NOD 1 and TLR 4 pathways in pericytes by pharmacological targeting of RIPK 2, a kinase involved in NOD 1 but not in TLR 4 signalling cascade. p38 MAPK and NF ‐κB appear to be downstream mediators in the NOD 1 pathway. In summary, these results indicate that pericytes can sense Gram‐negative bacterial products by both NOD 1 and TLR 4 receptors, acting through distinct pathways. This provides new insight about how brain pericytes participate in the inflammatory response and may have implications for disease management.