Document Detail


Highly purified lipoteichoic acid induced pro-inflammatory signalling in primary culture of rat microglia through Toll-like receptor 2: selective potentiation of nitric oxide production by muramyl dipeptide.
MedLine Citation:
PMID:  16879708     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In contrast to the role of lipopolysaccharide from Gram-negative bacteria, the role of Gram-positive bacterial components in inducing inflammation in the CNS remains controversial. We studied the potency of highly purified lipoteichoic acid and muramyl dipeptide isolated from Staphylococcus aureus to activate primary cultures of rat microglia. Exposure of pure microglial cultures to lipoteichoic acid triggered a significant time- and dose-dependent production of pro-inflammatory cytokines (tumour-necrosis factor-alpha, interleukin-1beta, interleukin-6) and nitric oxide. Muramyl dipeptide strongly and selectively potentiated lipoteichoic acid-induced inducible nitric oxide synthase expression and nitric oxide production. However, it did not have any significant influence on the production of pro-inflammatory cytokines. As bacterial components are recognised by the innate immunity through Toll-like receptors (TLRs) we showed that lipoteichoic acid was recognised in microglia by the TLR2 and lipopolysaccharide by the TLR4, as cells isolated from mice lacking TLR2 or TLR4 did not produce pro-inflammatory cytokines and nitric oxide upon lipoteichoic acid or lipopolysaccharide stimulation, respectively. Lipoteichoic acid-induced glia activation was mediated by p38 and ERK1/2 MAP kinases, as pretreatment with inhibitor of p38 or ERK1/2 decreased lipoteichoic acid-induced cytokine release, iNOS mRNA expression and nitric oxide production. The observed pro-inflammatory response induced by lipoteichoic acid-activated microglia could play a major role in the inflammatory response of CNS induced by Gram-positive bacteria.
Authors:
Agnieszka Kinsner; Monica Boveri; Lars Hareng; Guy C Brown; Sandra Coecke; Thomas Hartung; Anna Bal-Price
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-07-31
Journal Detail:
Title:  Journal of neurochemistry     Volume:  99     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-10     Completed Date:  2007-01-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  596-607     Citation Subset:  IM    
Affiliation:
European Centre for the Validation of Alternative Methods, ECVAM, European Commission Joint Research Centre, Ispra, VA, Italy.
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MeSH Terms
Descriptor/Qualifier:
Acetylmuramyl-Alanyl-Isoglutamine / immunology,  metabolism,  pharmacology*
Animals
Animals, Newborn
Cells, Cultured
Central Nervous System Bacterial Infections / immunology*,  metabolism
Cytokines / immunology,  metabolism,  secretion
Dose-Response Relationship, Drug
Encephalitis / immunology,  metabolism,  physiopathology
Enzyme Inhibitors / pharmacology
Extracellular Signal-Regulated MAP Kinases / drug effects,  metabolism
Inflammation Mediators / immunology,  metabolism,  pharmacology
Lipopolysaccharides / immunology,  pharmacology*
Microglia / drug effects,  immunology*,  metabolism
Nitric Oxide / metabolism*
Nitric Oxide Synthase Type II / drug effects,  genetics,  immunology
Rats
Signal Transduction / drug effects,  immunology
Teichoic Acids / immunology,  pharmacology*
Time Factors
Toll-Like Receptor 2 / drug effects,  metabolism*
Toll-Like Receptor 4 / drug effects,  immunology,  metabolism
p38 Mitogen-Activated Protein Kinases / drug effects,  metabolism
Chemical
Reg. No./Substance:
0/Cytokines; 0/Enzyme Inhibitors; 0/Inflammation Mediators; 0/Lipopolysaccharides; 0/Teichoic Acids; 0/Tlr2 protein, rat; 0/Tlr4 protein, rat; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 10102-43-9/Nitric Oxide; 53678-77-6/Acetylmuramyl-Alanyl-Isoglutamine; 56411-57-5/lipoteichoic acid; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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