Nucleotide oligomerization domain 1 is a dominant pathway for NOS2 induction in vascular smooth muscle cells: comparison with Toll-like receptor 4 responses in macrophages.

British Journal of Pharmacology
L MorenoJane A Mitchell

Abstract

Gram-negative bacteria contain ligands for Toll-like receptor (TLR) 4 and nucleotide oligomerization domain (NOD) 1 receptors. Lipopolysaccharide (LPS) activates TLR4, while peptidoglycan products activate NOD1. Activation of NOD1 by the specific agonist FK565 results in a profound vascular dysfunction and experimental shock in vivo. Here, we have analysed a number of pharmacological inhibitors to characterize the role of key signalling pathways in the induction of NOS2 following TLR4 or NOD1 activation. Vascular smooth muscle (VSM) cells expressed NOD1 mRNA and protein, and, after challenge with Escherichia coli or FK565, NOS2 protein and activity were induced. Macrophages had negligible levels of NOD1 and were unaffected by FK565, but responded to E. coli and LPS by releasing increased NO and expression of NOS2 protein. Classic pharmacological inhibitors for NF-kappaB (SC-514) and mitogen-activated protein kinase (SB203580, PD98059) signalling pathways inhibited responses in both cell types regardless of agonist. While TLR4-mediated responses in macrophages were specifically inhibited by the pan-caspase inhibitor z-VAD-fmk and the PKC inhibitor Gö6976, NOD1-mediated responses in VSM cells were inhibited by the Rip2 inhibitor ...Continue Reading

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Citations

May 26, 2012·Pharmacology & Therapeutics·M J Paul-ClarkJ A Mitchell
Sep 3, 2011·Immunological Reviews·Matthew T Sorbara, Dana J Philpott
Jul 16, 2013·British Journal of Pharmacology·L Moreno, T Gatheral
Jun 18, 2014·Clinical Science·Patricia PrietoMaría Fernández-Velasco
Apr 1, 2015·Cardiovascular Research·Carmen DelgadoMaria Fernández-Velasco
Nov 3, 2016·The Biochemical Journal·Almudena Val-BlascoMaría Fernández-Velasco
Dec 10, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shunsuke KannoToshiro Hara
Feb 18, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hirosuke InoueToshiro Hara
Feb 16, 2021·Frontiers in Cellular and Infection Microbiology·David K KessieRoy Gross
May 23, 2021·Acta Physiologica·Almudena Val-BlascoMaria Fernández-Velasco

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Methods Mentioned

BETA
lavage
PCR

Software Mentioned

Quantity One
Blast

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