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
Abstract
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‐α, interleukin‐1β, 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.
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Endotoxin directly and indirectly activates microglia that damage neurons via nitric oxide, oxidants and cytokines, and by phagocytosis of synapses and neurons.
“Endotoxin directly and indirectly activates microglia that damage neurons via nitric oxide, oxidants and cytokines, and by phagocytosis of synapses and neurons.”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [56]
Endotoxin stimulates microglia to produce nitric oxide and pro-inflammatory cytokines via activation of TLR4.
“Endotoxin stimulates microglia to produce nitric oxide and pro-inflammatory cytokines via activation of TLR4 [56].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [56]
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The endotoxin hypothesis of neurodegeneration
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- Authors
- Kinsner, A., Boveri, M., Hareng, L., Brown, G. C., Coecke, S., Hartung, T., & Bal‐Price, A.
- Affiliations
- European Commission (BE)
- University of Cambridge (GB)
- Corresponding author
- Bal‐Price, Anna
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2006-07-31
- Volume
- 99
- Issue
- 2
- Pages
- 596-607
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2121289311
- Cited by
- 59
- References
- 61
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 2 · 2021: 6 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 2
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- lipoteichoic acid, muramyl dipeptide, microglia, TLR2, TLR4, nitric oxide, inducible nitric oxide synthase, inflammatory cytokines, Staphylococcus aureus, p38 MAPK, ERK1/2 MAP kinase, innate immunity, neuroinflammation, lipopolysaccharide
- MeSH terms
- Acetylmuramyl-Alanyl-Isoglutamine, Animals, Animals, Newborn, Cells, Cultured, Dose-Response Relationship, Drug, Encephalitis, Enzyme Inhibitors, Lipopolysaccharides, Nitric Oxide, Teichoic Acids, Time Factors, Signal Transduction, Cytokines, Microglia, Inflammation Mediators, Central Nervous System Bacterial Infections, Extracellular Signal-Regulated MAP Kinases, p38 Mitogen-Activated Protein Kinases, Toll-Like Receptor 2, Toll-Like Receptor 4, Rats, Nitric Oxide Synthase Type II
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