論文

国際誌
2021年4月29日

Possible involvement of progranulin in the protective effect of elastase inhibitor on cerebral ischemic injuries of neuronal and glial cells.

Molecular and cellular neurosciences
  • Ichiro Horinokita
  • ,
  • Hideki Hayashi
  • ,
  • Rihona Yoshizawa
  • ,
  • Mika Ichiyanagi
  • ,
  • Yui Imamura
  • ,
  • Yui Iwatani
  • ,
  • Norio Takagi

113
開始ページ
103625
終了ページ
103625
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.mcn.2021.103625

In a previous study, we demonstrated that neutrophil elastase is activated in the brain parenchyma after cerebral ischemia, which enzyme cleaves progranulin (PGRN), an anti-inflammatory factor. In that study, we also found that sivelestat, a selective neutrophil elastase inhibitor, attenuates ischemia-induced inflammatory responses. However, it was not clear whether this anti-inflammatory effect was due to the direct effect of sivelestat. In this study, we evaluated the effects of sivelestat or recombinant PGRN (rPGRN) on cell injuries in cultured neurons, astrocytes, and microglia under oxygen/glucose deprivation (OGD) conditions. We demonstrated that OGD-induced neuronal cell injury, astrocyte activation, and increased proinflammatory cytokines caused by microglial activation, were suppressed by rPGRN treatment, whereas sivelestat had no effect on any of these events. These results indicate that the anti-inflammatory responses after in vivo cerebral ischemia were not due to the direct action of sivelestat but due to the suppression of PGRN cleavage by inhibition of elastase activity. It was also suggested that the pleiotropic effect of rPGRN could be attributed to the differentiation of M1 microglia into anti-inflammatory type M2 microglia. Therefore, the inhibition of PGRN cleavage by sivelestat could contribute to the establishment of a new therapeutic approach for cerebral ischemia.

リンク情報
DOI
https://doi.org/10.1016/j.mcn.2021.103625
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33933589
ID情報
  • DOI : 10.1016/j.mcn.2021.103625
  • PubMed ID : 33933589

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