| RRC ID |
35703
|
| 著者 |
Ito M, Shichita T, Okada M, Komine R, Noguchi Y, Yoshimura A, Morita R.
|
| タイトル |
Bruton's tyrosine kinase is essential for NLRP3 inflammasome activation and contributes to ischaemic brain injury.
|
| ジャーナル |
Nat Commun
|
| Abstract |
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.
|
| 巻・号 |
6
|
| ページ |
7360
|
| 公開日 |
2015-6-10
|
| DOI |
10.1038/ncomms8360
|
| PII |
ncomms8360
|
| PMID |
26059659
|
| PMC |
PMC4490404
|
| MeSH |
Agammaglobulinaemia Tyrosine Kinase
Animals
Brain Ischemia / metabolism*
Carrier Proteins / metabolism*
Inflammasomes / metabolism*
Mice
NLR Family, Pyrin Domain-Containing 3 Protein
Protein Kinase Inhibitors / pharmacology
Protein-Tyrosine Kinases / antagonists & inhibitors
Protein-Tyrosine Kinases / metabolism*
|
| IF |
12.121
|
| 引用数 |
136
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 遺伝子材料 |
CSII-EF-MCS-IRES2-Venus (RDB04384)
pCMV-VSV-G-RSV-Rev (RDB04393). |
| ヒト・動物細胞 |
THP-1(RCB1189)
293(RCB1637) |
