title: Lansoprazole inhibits nitric oxide and prostaglandin E(2) production in murine macrophage RAW 264.7 cells.
abstract: Aberrantly activated macrophages, which overproduce inflammatory mediators, are involved in the pathogenesis of many inflammatory diseases. We analyzed the anti-inflammatory activity of lansoprazole (LPZ), a typical proton pump (P-ATPase) inhibitor, on RAW264.7 murine macrophages. Treatment of lipopolysaccharide (LPS)-stimulated RAW264.7 cells with LPZ inhibited the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)). Since P-ATPase expression was not observed in RAW264.7 cells, the anti-inflammatory effect of LPZ was independent of ATPase. In contrast, diphenylene iodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, decreased NO but not PGE(2) levels. LPZ suppressed the LPS-stimulated production by RAW264.7 cells of reactive oxygen species (ROS), which plays an important role in inflammatory responses. ROS elevation in these cells was associated with NO but not PGE(2) production, suggesting that LPZ inhibits NO production by suppressing NADPH oxidase activity. These findings suggest that LPZ may be useful in the treatment of many inflammatory diseases associated with activated macrophages.
authors: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors: Shuji
authors: S
authors: Nakagawa
authors: Yuji
authors: Y
authors: Arai
authors: Tsunao
authors: T
authors: Kishida
authors: Nobuyuki
authors: N
authors: Hiraoka
authors: Shinji
authors: S
authors: Tsuchida
authors: Hiroaki
authors: H
authors: Inoue
authors: Ryo
authors: R
authors: Sakai
authors: Osam
authors: O
authors: Mazda
authors: Toshikazu
authors: T
authors: Kubo
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D015232:Dinoprostone / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D064747:Lansoprazole; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000096:biosynthesis*; D009861:Onium Compounds / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009861:Onium Compounds; D054328:Proton Pump Inhibitors; D017382:Reactive Oxygen Species; D064747:Lansoprazole; D009569:Nitric Oxide; C007517:diphenyleneiodonium; D019255:NADPH Oxidases; D015232:Dinoprostone