オオシロ サトル
  大城 聰   スポーツ・健康科学部 健康科学科   教授
■ 標題
  Superoxide anion contributes to the induction of tumor necrosis factor alpha thorough activation of the MKK3/6p38 MAPK cacade in ragt microglia.
■ 概要
  Stimulation of rat microglia with lipopolysaccharide (LPS) in vitro induces production of the inflammatory/cytotoxic cytokine tumor necrosis factor alpha (TNFa) along with superoxide anion O2- and nitric oxide (NO). In this study, we investigated the role and O2-and NO in the induction of TNFa in microglia. The LPS-inducible TNFa was significantly suppressed by pretreatment with the O2- scavenger N-acetyl cysteine (NAC), but not by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl imidazoline-1-oxy 3-oxide, suggesting the close association of O2- with TNFa induction. NAC strongly depressed phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which is necessary for inducing TNFa in microglia, On the other hand, an O2-donor, 3-(4-morphonyl) sydnonimine (SIN-1), induced TNFa in microglia, and the effects of SIN-1 were completely abolished in the presence of superoxide dismutase. There is little likelihood that the NO production in SIN-1 degradation induces TNFa in microglia, because TNFa was not induced in microglia exposed to the NO-donor S-nitroso-N-acetyl -dl- penicillamine. Moreover, the addition of SIN-1 to microglia resulted in activation of p38 MAPK and upstream kinase MKK3/6-p38 cascade, which is requisite for inducing TNFa in micrglia.
  ◎Yoshino Y, Yamamoto S, Kohsaka S, Oshiro S, Nakajima K.
  共著   Brain Res.   Elsevier   1422,1-12頁   2011/11


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