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    题名: Anti-inflammatory effects of dimemorfan on inflammatory cells and LPS-induced endotoxin shock in mice
    作者: Wang, Y.H.
    Shen, Y.C.
    Liao, J.F.
    Li, C.H.
    Chou, C.Y.
    Liou, K.T.
    Chou, Y.C.
    贡献者: 國術系
    关键词: cytokine
    dimemorfan
    endotoxin shock
    iNOS
    microglial cells
    neutrophils
    NF-kappa B
    NO
    ROS
    日期: 2008
    上传时间: 2009-11-09 16:08:00 (UTC+8)
    摘要: Background and purpose: Dimemorfan (a sigma(1) receptor agonist) showed neuroprotective properties in animal models of inflammation-mediated neurodegenerative conditions, but its effects on inflammatory cells and systemic inflammation remain unclear.
    Experimental approach: The effects of dimemorfan on phorbol-12-myristate-13-acetate (PMA)- and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophils and lipopolysaccharide (LPS)-activated microglial cells, as well as LPSinduced endotoxin shock in mice were elucidated.

    Key results: Dimemorfan decreased PMA- and fMLP-induced production of reactive oxygen species (ROS) and CD11b expression in neutrophils, through mechanisms independent of s1 receptors, possibly by blocking ROS production and G-protein-mediated intracellular calcium increase. Dimemorfan also inhibited LPS-induced ROS and nitric oxide (NO) production, as well as that of monocyte chemoattractant protein-1 and tumour necrosis factor-alpha (TNF-alpha), by inhibition of NADPH oxidase (NOX) activity and suppression of iNOS up-regulation through interfering with nuclear factor kappa-B (NF-kappa B) signalling in microglial cells. Treatment in vivo with dimemorfan (1 and 5 mg kg(-1), i.p., at three successive times after LPS) decreased plasma TNF-alpha, and neutrophil infiltration and oxidative stress in the lung and liver.

    Conclusions and implications: Our results suggest that dimemorfan acts via s1 receptor-independent mechanisms to modulate intracellular calcium increase, NOX activity, and NF-kappa B signalling, resulting in inhibition of iNOS expression and NO production, and production of pro-inflammatory cytokines. These effects may contribute its anti-inflammatory action and protective effects against endotoxin shock in mice.
    關聯: BRITISH JOURNAL OF PHARMACOLOGY Volume: 154 Issue: 6 Pages: 1327-1338
    显示于类别:[技擊運動暨國術學系] 期刊論文

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