title: 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: Department of Neurology Philipps-University of Marburg, Baldingerstraße 1, 35043 Marburg, Germany.
authors: Levke
authors: L
authors: Steiner
authors: Department of Neurology Philipps-University of Marburg, Baldingerstraße 1, 35043 Marburg, Germany.
authors: Maike
authors: M
authors: Gold
authors: Department of Neurology Philipps-University of Marburg, Baldingerstraße 1, 35043 Marburg, Germany.
authors: David
authors: D
authors: Mengel
authors: Department of Neurology Philipps-University of Marburg, Baldingerstraße 1, 35043 Marburg, Germany.
authors: Richard
authors: R
authors: Dodel
authors: Department of Neurology Philipps-University of Marburg, Baldingerstraße 1, 35043 Marburg, Germany. Electronic address: bachjan@staff.uni-marburg.de.
authors: Jan-Philipp
authors: JP
authors: Bach
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D002461:Cell Line, Transformed; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D018691:Excitatory Amino Acid Antagonists; D015850:Interleukin-6 / Q000378:metabolism; D007736:Kynurenic Acid / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018691:Excitatory Amino Acid Antagonists; D015850:Interleukin-6; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; C075222:amyloid beta-protein (1-42); D009569:Nitric Oxide; D007736:Kynurenic Acid
keywords: Alzheimer disease; Inflammation; Kynurenic acid; Microglia; Phagocytosis; α7 nicotinic acetylcholine receptor