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

Amyloid-beta has been shown to interact with the alpha 7 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 alpha 7 nicotinic acetylcholine receptor antagonist lcynurenic acid. Our aim was to investigate the effect of kynurenic acid on amyloid-beta-treated BV-2 microglial cells with respect to alpha 7 nicotinic acetylcholine receptor expression, cell viability, cytokine production and phagocytotic abilities. Therefore BV-2 cells were treated with oligomeric or fibrillar forms of amyloid-beta(1-40) and co-treated with kynurenic add. alpha 7 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-beta uptake were investigated with fluorescence-activated cell sorting and verified by Western blotting. Amyloid-beta nor kynurenic acid did have an effect on the protein level of the alpha 7 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-alpha and IL-6 and amyloid-beta phagocytosis. We provide evidence for an immunomodulating effect of the endogenous alpha 7 nicotinic acetylcholine receptor antagonist kynurenic acid. Our findings indicate a role for kynurenic add in amyloid-beta associated neuroinflammation in Alzheimer disease. (C) 2014 Elsevier B.V. All rights reserved.