The endogenous α7 nicotinic acetylcholine receptor antagonist kynurenic acid modulates amyloid-β-induced inflammation in BV-2 microglial cells.

Abstract

Amyloid-β has been shown to interact with the α7 nicotinic acetylcholine receptor on neuronal cells. Not much is known on the effect on microglial cells and whether this effect can be modulated by the endogenous α7 nicotinic acetylcholine receptor antagonist kynurenic acid. Our aim was to investigate the effect of kynurenic acid on amyloid-β-treated BV-2 microglial cells with respect to α7 nicotinic acetylcholine receptor expression, cell viability, cytokine production and phagocytotic abilities. Therefore BV-2 cells were treated with oligomeric or fibrillar forms of amyloid-β(1-40) and co-treated with kynurenic acid. α7 nicotinic acetylcholine receptor quantity was investigated using Western blotting. Cell viability was assessed by staining cells with fluorescein diacetate and propidium iodide. Pro-inflammatory cytokines were measured in cell culture supernatants of treated cells with ELISAs; NO with Griess reagents and amyloid-β uptake were investigated with fluorescence-activated cell sorting and verified by Western blotting. Amyloid-β nor kynurenic acid did have an effect on the protein level of the α7 nicotinic acetylcholine receptor. Amyloid-Beta induced cell mortality was unchanged after addition of kynurenic acid. However, kynurenic acid co-treatment reduced the pro-inflammatory cytokines tumour necrosis factor-α and IL-6 and amyloid-β phagocytosis. We provide evidence for an immunomodulating effect of the endogenous α7 nicotinic acetylcholine receptor antagonist kynurenic acid. Our findings indicate a role for kynurenic acid in amyloid-β associated neuroinflammation in Alzheimer disease.

• Authors: Levke Steiner, Maike Gold, David Mengel, Richard Dodel, Jan-Philipp Bach
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 344 Issue 1-2 Pg. 94-9 (Sep 15 2014) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 25064444 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Excitatory Amino Acid Antagonists
• Interleukin-6
• Peptide Fragments
• Tumor Necrosis Factor-alpha
• alpha7 Nicotinic Acetylcholine Receptor
• amyloid beta-protein (1-42)
• Nitric Oxide
• Kynurenic Acid

Topics

• Amyloid beta-Peptides (pharmacology)
• Animals
• Cell Line, Transformed
• Cell Survival
• Dose-Response Relationship, Drug
• Enzyme-Linked Immunosorbent Assay
• Excitatory Amino Acid Antagonists
• Interleukin-6 (metabolism)
• Kynurenic Acid (pharmacology)
• Mice
• Mice, Inbred C57BL
• Microglia (drug effects)
• Nitric Oxide (metabolism)
• Peptide Fragments (pharmacology)
• Phagocytosis (drug effects)
• Tumor Necrosis Factor-alpha (metabolism)
• alpha7 Nicotinic Acetylcholine Receptor (antagonists & inhibitors, metabolism)