Inhibition of inducible nitric oxide synthase gene expression by indomethacin or ibuprofen in beta-amyloid protein-stimulated J774 cells

Recent studies show that a mononuclear phagocyte lineage, including microgl ia, plays a possible role in the pathogenesis of Alzheimer's disease throug h nitric oxide (NO)-mediated neurotoxicity. Epidemiological studies show th at nonsteroidal anti-inflammatory drugs (NSAIDs) have a protective effect a gainst Alzheimer's disease. Based on these observations, it has been hypoth esized that an anti-Alzheimer's disease effect of NSAIDs could result from the inhibition of NO synthesis. We report here that indomethacin or ibuprof en dose-dependently reduce beta -amyloid protein and interferon-gamma -indu ced NO production, accompanied by an inhibition of inducible nitric oxide s ynthase mRNA expression in J774 cells, a murine macrophage cell line. Aspir in, however, does not produce such an effect, suggesting that the cyclooxyg enases pathway is not involved in the inhibitory effects of NSAIDs on beta -amyloid protein and interferon-gamma -induced NO production in J774 cells. (C) 2000 Elsevier Science B.V. All rights reserved.