ミクログリアにおけるヘモグロビン誘導膜結合型プロスタグランジンE合成酵素-1は炎症と神経細胞死に寄与する

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  • Microsomal prostaglandin E synthase-1 induced by hemoglobin in microglia contributes to inflammation and neuronal death

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<p>We have previously demonstrated that microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal enzyme for PGE2 synthesis, aggravates brain inflammation and neurotoxicity in collagenase-induced intracerebral hemorrhage (ICH) mice. In this study, we investigated the role of microglial mPGES-1 in the hemoglobin (Hb)-induced inflammatory responses and neurotoxicity in vitro. At first, we investigated the effect of Hb on mPGES-1 induction and PGE2 production using neuronal cell line, SH-SY5Y cells and microglial cell line, BV-2 cells. mPGES-1 was significantly induced by Hb in BV-2 cells, but not in SH-SY5Y cells. PGE2 production after Hb exposure was increased in BV-2 cells but decreased in SH-SY5Ycells. Therefore, we next investigated the role of microglial mPGES-1 in Hb responses using primary microglial culture obtained from Wild-type (WT) and mPGES-1 knock out (KO) mice. Hb significantly increased PGE2 production in WT microglia, but not in mPGES-1 KO microglia. The Hb-induced mRNA expressions of TNF-α and IL-1β in mPGES-1 KO microglia were significantly less than those in WT microglia. Furthermore, Hb-induced neurotoxicity of cortical neurons cocultured with mPGES-1 KO microglia was less severe than that cocultured with WT microglia. These results suggest that microglial mPGES-1 contributes to neuronal death after ICH through PGE2 production and regulation of inflammatory cytokines. Thus, mPGES-1 may be a promising therapeutic target for the treatment of ICH.</p>

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