| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
Aberrantly activated macrophages, which overproduce inflammatory mediators, are involved in the pathogenesis of many inflammatory diseases, such as rheumatoid arthritis. 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 E2(PGE2). 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 PGE2 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 PGE2 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.
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