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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Cell+Mol+Med
2016 ; 20
(5
): 980-6
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Role of nucleotide-binding oligomerization domain 1 (NOD1) in pericyte-mediated
vascular inflammation
#MMPMID26915562
Navarro R
; Delgado-Wicke P
; Nuñez-Prado N
; Compte M
; Blanco-Toribio A
; Nuñez G
; Álvarez-Vallina L
; Sanz L
J Cell Mol Med
2016[May]; 20
(5
): 980-6
PMID26915562
show ga
We have recently described the response of human brain pericytes to
lipopolysaccharide (LPS) through toll-like receptor 4 (TLR4). 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 NOD1 and NOD2 in HBP and compare
the responses to their cognate agonists and ultrapure LPS. Our findings show for
the first time that NOD1 is expressed in pericytes, whereas NOD2 expression is
barely detectable. The NOD1 agonist C12-iE-DAP induced IL6 and IL8 gene
expression by pericytes as well as release of cytokines into culture supernatant.
Moreover, we demonstrated the synergistic effects of NOD1 and TLR4 agonists on
the induction of IL8. Using NOD1 silencing in HBP, we showed a requirement for
C12-iE-DAP-dependent signalling. Finally, we could discriminate NOD1 and TLR4
pathways in pericytes by pharmacological targeting of RIPK2, a kinase involved in
NOD1 but not in TLR4 signalling cascade. p38 MAPK and NF-?B appear to be
downstream mediators in the NOD1 pathway. In summary, these results indicate that
pericytes can sense Gram-negative bacterial products by both NOD1 and TLR4
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.