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

Recent studies show that a mononuclear phagocyte lineage, including microglia, plays a possible role in the pathogenesis of Alzheimer's disease through nitric oxide (NO)-mediated neurotoxicity. Epidemiological studies show that nonsteroidal anti-inflammatory drugs (NSAIDs) have a protective effect against Alzheimer's disease. Based on these observations, it has been hypothesized that an anti-Alzheimer's disease effect of NSAIDs could result from the inhibition of NO synthesis. We report here that indomethacin or ibuprofen dose-dependently reduce beta -amyloid protein and interferon-gamma -induced NO production, accompanied by an inhibition of inducible nitric oxide synthase mRNA expression in J774 cells, a murine macrophage cell line. Aspirin, however, does not produce such an effect, suggesting that the cyclooxygenases 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.