論文 - 詳細
| RRC ID | 58073 |
|---|---|
| 著者 | Suzuki T, Kohyama K, Moriyama K, Ozaki M, Hasegawa S, Ueno T, Saitoe M, Morio T, Hayashi M, Sakuma H. |
| タイトル | Extracellular ADP augments microglial inflammasome and NF-κB activation via the P2Y12 receptor. |
| ジャーナル | Eur J Immunol |
| Abstract |
The NLRP3 inflammasome is a molecular complex that translates signals from pathogens and tissue damage into inflammatory responses, and plays crucial roles in numerous neurological diseases. Activation of the NLRP3 inflammasome leads to caspase-1 dependent cleavage of pro-IL-1β to form mature IL-1β. By acting on the P2X7 purinergic receptor, extracellular ATP is one of the major stimuli that activates the NLRP3 inflammasome. Although microglia express multiple purinergic receptors, their roles in inflammasome-mediated inflammation are largely unknown. We studied the role of the P2Y12 receptor, a metabotropic P2Y receptor enriched in microglia, on inflammation in vitro. Inhibition of the microglial P2Y12 receptor by PSB0739 or siRNA knockdown suppressed IL-1β release. P2Y12 receptor-deficient microglia displayed markedly attenuated IL-1β mRNA expression and release. P2Y12 receptor blockade also suppressed IL-6 production. Both IL-1β and IL-6 responses were augmented by extracellular ADP or ADP-βS and were abrogated by PSB0739. Mechanistically, ADP-βS potentiated NF-κB activation. In addition, ADP altered mitochondrial membrane potential in combination with ATP and increased the number of caspase-1 positive cells through the P2Y12 receptor. These results elucidate a novel inflammatory mechanism by which extracellular ADP acts on the P2Y12 receptor to activate NF-κB and the NLRP3 inflammasome to enhance microglial inflammation. |
| 巻・号 | 50(2) |
| ページ | 205-219 |
| 公開日 | 2020-2-1 |
| DOI | 10.1002/eji.201848013 |
| PMID | 31549730 |
| MeSH | Adenosine Diphosphate / metabolism* Animals Caspase 1 / metabolism Cell Line Cytokines / metabolism Gene Expression Regulation / physiology Inflammasomes / metabolism* Inflammation / metabolism Inflammation Mediators / metabolism Interleukin-1beta / metabolism Macrophages / metabolism Mice NF-kappa B / metabolism* Reactive Oxygen Species / metabolism Receptors, Purinergic P2Y12 / metabolism* Signal Transduction / physiology |
| IF | 4.404 |
| 引用数 | 1 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Peer-review(Publons) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MG6(RCB2403) |