論文 - 詳細
| RRC ID | 51754 |
|---|---|
| 著者 | Ando T, Komatsu T, Naiki Y, Takahashi K, Yokochi T, Watanabe D, Koide N. |
| タイトル | GSK2656157, a PERK inhibitor, reduced LPS-induced IL-1β production through inhibiting Caspase 1 activation in macrophage-like J774.1 cells. |
| ジャーナル | Immunopharmacol Immunotoxicol |
| Abstract |
IL-1β is one of the inflammatory cytokines and is cleaved from pro-IL-1β proteolytically by activated Caspase 1. For the activation of Caspase 1, inflammasome was formed by two signals, what is called, priming and triggering signals. In this study, it was found that mouse macrophage J774.1 cells, when treated by single large amount of lipopolysaccharide (LPS), produced a significant amount of IL-1β. On the other hand, IL-1β production was not detected when treated by a single, small amount of LPS. Then, focusing on endoplasmic reticulum (ER) stress response among stress responses induced by a large amount of LPS, when GSK2656157, a PERK inhibitor, was used for inhibition of ER stress, GSK2656157 reduced IL-1β production dose-dependently. Next, when Thapsigargin, an ER stress reagent, was added with LPS, IL-1β production increased more than by LPS alone. Thus, these results suggested that ER stress was involved in LPS-induced IL-1β production. When the activation of Caspase 1 was examined by fluorescence activated cell sorter analysis, it was found that GSK2656157 inhibited LPS-induced Caspase 1 activation. Further, it was confirmed that GSK2656157 did not affect LPS-induced TNF-α production and activation of NF-κB and specifically inhibited the PERK/eIF-2α pathway. Therefore, it was found that GSK2656157 specifically inhibited ER stress induced by large amount of LPS and reduced LPS-induced IL-1β production through inhibition of Caspase 1 activation. |
| 巻・号 | 38(4) |
| ページ | 298-302 |
| 公開日 | 2016-8-1 |
| DOI | 10.1080/08923973.2016.1192191 |
| PMID | 27251848 |
| MeSH | Adenine / analogs & derivatives* Adenine / pharmacology Animals Caspase 1 / immunology* Cell Line Enzyme Activation / drug effects Enzyme Activation / immunology Indoles / pharmacology* Interleukin-1beta / immunology* Lipopolysaccharides / toxicity* Macrophages / immunology* Mice eIF-2 Kinase / antagonists & inhibitors* |
| IF | 2.352 |
| 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 | F1000Research |
| 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 | J774.1(RCB0434) |