論文 - 詳細
| RRC ID | 18208 |
|---|---|
| 著者 | Takenouchi T, Iwamaru Y, Sugama S, Tsukimoto M, Fujita M, Sekigawa A, Sekiyama K, Sato M, Kojima S, Conti B, Hashimoto M, Kitani H. |
| タイトル | The activation of P2X7 receptor induces cathepsin D-dependent production of a 20-kDa form of IL-1β under acidic extracellular pH in LPS-primed microglial cells. |
| ジャーナル | J Neurochem |
| Abstract |
The potent pro-inflammatory cytokine, interleukin-1β (IL-1β), is synthesized as an inactive 33-kDa precursor (pro-IL-1β) and is processed by caspase 1 into the bioactive 17-kDa mature form. The P2X7 receptor, an ATP-gated cation channel, plays an essential role in caspase 1 activation, production and release of mature bioactive 17-kDa form. We recently reported ATP induces the release of an unconventional 20-kDa form of IL-1β (p20-IL-1β) from lipopolysaccharide-primed microglial cells. Emerging evidence suggests physiological relevance for p20-IL-1β; however, the underlying mechanisms for its production and release remain unknown. Here, we investigated the pathways involved in the ATP-induced production of p20-IL-1β using lipopolysaccharide-primed mouse microglial cells. The activation of P2X7 receptor by ATP triggered p20-IL-1β production under acidic extracellular conditions. ATP-induced p20-IL-1β production was blocked by pepstatin A, a potent inhibitor of the lysosomal protease, cathepsin D. The removal of extracellular Ca(2+) inhibited the p20-IL-1β production as well as ATP-induced cathepsin D release via lysosome exocytosis. The acidic extracellular pH also facilitated the dilatation of membrane pore after ATP stimulation. Since facilitation of pore dilatation results in cytolysis accompanied with cytoplasmic pro-IL-1β leakage, our data suggest the leaked pro-IL-1β is processed into p20-IL-1β by cathepsin D released after ATP stimulation under acidic extracellular conditions. |
| 巻・号 | 117(4) |
| ページ | 712-23 |
| 公開日 | 2011-5-1 |
| DOI | 10.1111/j.1471-4159.2011.07240.x |
| PMID | 21395581 |
| MeSH | Adenosine Triphosphate / pharmacology Animals Blotting, Western Caspase 1 / metabolism Cathepsin D / pharmacology* Cell Line Exocytosis / drug effects Extracellular Space / metabolism* Hydrogen-Ion Concentration Immunohistochemistry Interleukin-1beta / biosynthesis* Lipopolysaccharides / pharmacology* Lysosomes / drug effects Lysosomes / metabolism Mice Mice, Inbred C57BL Microglia / drug effects Microglia / metabolism* Nerve Tissue Proteins / biosynthesis Pepstatins / pharmacology Receptors, Purinergic P2X7 / drug effects* |
| IF | 4.066 |
| 引用数 | 24 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY NEUROSCIENCES |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 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) |