Bruton's tyrosine kinase is essential for NLRP3 inflammasome activation and contributes to ischaemic brain injury

Minako Ito, Takashi Shichita, Masahiro Okada, Ritsuko Komine, Yoshiko Noguchi, Akihiko Yoshimura, Rimpei Morita

研究成果: Contribution to journalArticle査読

197 被引用数 (Scopus)

抄録

Inflammasome activation has been implicated in various inflammatory diseases including post-ischaemic inflammation after stroke. Inflammasomes mediate activation of caspase-1, which subsequently induces secretion of pro-inflammatory cytokines such as IL-1β and IL-18, as well as a form of cell death called pyroptosis. In this study, we report that Bruton's tyrosine kinase (BTK) is an essential component of the NLRP3 inflammasome, in which BTK physically interacts with ASC and NLRP3. Inhibition of BTK by pharmacological or genetic means severely impairs activation of the NLRP3 inflammasome. The FDA-approved BTK inhibitor ibrutinib (PCI-32765) efficiently suppresses infarct volume growth and neurological damage in a brain ischaemia/reperfusion model in mice. Ibrutinib inhibits maturation of IL-1β by suppressing caspase-1 activation in infiltrating macrophages and neutrophils in the infarcted area of ischaemic brain. Our study indicates that BTK is essential for NLRP3 inflammasome activation and could be a potent therapeutic target in ischaemic stroke.

本文言語英語
論文番号7360
ジャーナルNature communications
6
DOI
出版ステータス出版済み - 6 10 2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

フィンガープリント

「Bruton's tyrosine kinase is essential for NLRP3 inflammasome activation and contributes to ischaemic brain injury」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル