title: Inhibition of inducible nitric oxide synthase gene expression by indomethacin or ibuprofen in beta-amyloid protein-stimulated J774 cells.
abstract: 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.
authors.affiliation: Department of Geriatrics, Graduate School of Medicine, Nagoya University, 65 Tsuruma-Cho, Showa-Ku, Aichi, 466-8550, Nagoya, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Ogawa
authors.forename: H
authors.initials: H
authors.lastname: Umegaki
authors.forename: D
authors.initials: D
authors.lastname: Sumi
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: A
authors.initials: A
authors.lastname: Nakamura
authors.forename: N K
authors.initials: NK
authors.lastname: Thakur
authors.forename: J
authors.initials: J
authors.lastname: Yoshimura
authors.forename: H
authors.initials: H
authors.lastname: Endo
authors.forename: A
authors.initials: A
authors.lastname: Iguchi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D007052:Ibuprofen / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007371:Interferon-gamma / Q000187:drug effects / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D007052:Ibuprofen; D007213:Indomethacin