Abstract |
The interaction of endogenous and exogenous stimulators of innate immunity was examined in primary cultures of mouse microglial cells and macrophages after application of defined Toll-like receptor ( TLR) agonists [ lipopolysaccharide (LPS) (TLR4), the synthetic lipopeptide Pam3Cys-Ser-Lys4 ( Pam3Cys) (TLR2) and single-stranded unmethylated CpG- DNA (CpG) (TLR9)] alone and in combination with amyloid beta peptide (Abeta) 1-40. Abeta1-40 stimulated microglial cells and macrophages primed by interferon-gamma in a dose-dependent manner. Co-administration of Abeta1-40 with LPS or Pam3Cys led to an additive release of nitric oxide (NO) and tumour necrosis factor alpha ( TNF-alpha). This may be one reason for the clinical deterioration frequently observed in patients with Alzheimer's disease during infections. In contrast, co-application of Abeta1-40 with CpG led to a substantial decrease of NO and TNF-alpha release compared with stimulation with CpG alone. Abeta1-40 and CpG did not co-localize within the same subcellular compartment, making a direct physicochemical interaction as the cause of the observed antagonism very unlikely. This suggests that not all TLR agonists enhance the stimulatory effect of A beta on innate immunity.
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Authors | Miriam Lotz, Sandra Ebert, Hermann Esselmann, Asparouh I Iliev, Marco Prinz, Nicole Wiazewicz, Jens Wiltfang, Joachim Gerber, Roland Nau |
Journal | Journal of neurochemistry
(J Neurochem)
Vol. 94
Issue 2
Pg. 289-98
(Jul 2005)
ISSN: 0022-3042 [Print] England |
PMID | 15998280
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amyloid beta-Peptides
- CpG-DNA, E coli
- Cytokines
- DNA, Bacterial
- DNA-Binding Proteins
- Lectins
- Lipopolysaccharides
- Lipoproteins
- Nitrites
- Peptide Fragments
- Receptors, Cell Surface
- Receptors, Immunologic
- Tlr2 protein, mouse
- Tlr4 protein, mouse
- Tlr9 protein, mouse
- Toll-Like Receptor 2
- Toll-Like Receptor 4
- Toll-Like Receptor 9
- amyloid beta-protein (1-40)
- N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine
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Topics |
- Amyloid beta-Peptides
(metabolism, pharmacology)
- Analysis of Variance
- Animals
- Animals, Newborn
- Blotting, Western
(methods)
- Brain
(cytology)
- Cell Survival
(drug effects)
- Cells, Cultured
- Cytokines
(metabolism)
- DNA, Bacterial
(pharmacology)
- DNA-Binding Proteins
(antagonists & inhibitors)
- Dose-Response Relationship, Drug
- Drug Interactions
- Enzyme-Linked Immunosorbent Assay
(methods)
- Immunohistochemistry
(methods)
- Inflammation
(chemically induced, physiopathology)
- Lectins
(metabolism)
- Lipopolysaccharides
(pharmacology)
- Lipoproteins
(pharmacology)
- Macrophages
(drug effects)
- Mice
- Mice, Inbred C57BL
- Microglia
(drug effects, physiology)
- Microscopy, Confocal
(methods)
- Nitrites
(metabolism)
- Peptide Fragments
(metabolism, pharmacology)
- Receptors, Cell Surface
(antagonists & inhibitors)
- Receptors, Immunologic
(agonists)
- Toll-Like Receptor 2
- Toll-Like Receptor 4
- Toll-Like Receptor 9
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