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

• Published in: European journal of pharmacology 2000-11, Vol.408 (2), p.137-141
• Main Authors: Ogawa, Osamu, Umegaki, Hiroyuki, Sumi, Daigo, Hayashi, Toshio, Nakamura, Akira, Thakur, Navin Kumar, Yoshimura, Juri, Endo, Hidetoshi, Iguchi, Akihisa
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer's disease; Amyloid beta-Peptides - drug effects; Amyloid beta-Peptides - pharmacology; Animals; Antineoplastic Agents - pharmacology; Aspirin; Biological and medical sciences; Cell Line; Cyclooxygenase Inhibitors - pharmacology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Enzymologic - physiology; Ibuprofen - pharmacology; Indomethacin - pharmacology; Interferon-gamma - drug effects; Interferon-gamma - pharmacology; Interferon-γ; Medical sciences; Microglia; Neurology; Neuropharmacology; Neuroprotective agent; Nitric Oxide Synthase - drug effects; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; NSAIDs; Pharmacology. Drug treatments; RNA, Messenger - drug effects; RNA, Messenger - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(00)00721-4

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 β-amyloid protein and interferon-γ-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 β-amyloid protein and interferon-γ-induced NO production in J774 cells.