Muramyl dipeptide potentiates cytokine-induced activation of inducible nitric oxide synthase in rat astrocytes.

Abstract:

:We investigated the influence of muramyl dipeptide (MDP), a cell wall component of Gram-positive bacteria, on cytokine-induced nitric oxide (NO) production in rat primary astrocytes. MDP alone did not induce NO release in astrocyte cultures. However, MDP increased astrocyte NO production and subsequent nitrite accumulation triggered by IFN-gamma. IFN-gamma-activated expression of mRNA for inducible NO synthase (iNOS) and iNOS transcription factor interferon regulatory factor-1 (IRF-1) was markedly enhanced in astrocytes treated with MDP. The potentiating effect of MDP on IFN-gamma-induced NO production in astrocytes was completely blocked with protein tyrosine kinase (PTK) inhibitor genistein or mitogen activated protein kinase (MAPK) inhibitor PD98059. In contrast, protein kinase C (PKC) inhibitor calphostin C did not affect ability of MDP to augment IFN-gamma-triggered astrocyte NO synthesis. These results suggest that MDP synergizes with IFN-gamma in the induction of iNOS gene in astrocytes through mechanisms involving PTK and MAPK, but not PKC activation. Finally, MDP also augmented NO production and iNOS mRNA expression in astrocytes treated with IL-1beta.

journal_name

Brain Res

journal_title

Brain research

authors

Trajkovic V,Samardzic T,Stosic-Grujicic S,Ramic Z,Mostarica Stojkovic M

doi

10.1016/s0006-8993(00)02920-6

subject

Has Abstract

pub_date

2000-11-10 00:00:00

pages

157-63

issue

1

eissn

0006-8993

issn

1872-6240

pii

S0006899300029206

journal_volume

883

pub_type

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