論文 - 詳細
| RRC ID | 38475 |
|---|---|
| 著者 | Tanaka N, Abe-Dohmae S, Iwamoto N, Fitzgerald ML, Yokoyama S. |
| タイトル | HMG-CoA reductase inhibitors enhance phagocytosis by upregulating ATP-binding cassette transporter A7. |
| ジャーナル | Atherosclerosis |
| Abstract |
We recently reported that the endogenous ATP-binding cassette transporter (ABC) A7 strongly associates with phagocytosis, being regulated by sterol regulatory element binding protein 2. We therefore examined the effect of statins on phagocytosis in vitro and in vivo through the SREBP-ABCA7. Phagocytosis was found to be enhanced by pravastatin, rosuvastatin and simvastatin and cyclodextrin in J774 macrophages, as cellular cholesterol was reduced and expressions of the cholesterol-related genes were modulated, including an increase of ABCA7 mRNA and decrease of ABCA1 mRNA. Conversely, knock-down of ABCA7 expression by siRNA ablated enhancement of phagocytosis by statins. In vivo, pravastatin enhanced phagocytosis in wild-type mice, but not in ABCA7-knockout mice. We thus concluded that statins enhance phagocytosis through the SREBP-ABCA7 pathway. These findings provide a molecular basis for enhancement of the host-defense system by statins showing that one of their "pleiotropic" effects is in fact achieved through their reaction to a primary target. |
| 巻・号 | 217(2) |
| ページ | 407-14 |
| 公開日 | 2011-8-1 |
| DOI | 10.1016/j.atherosclerosis.2011.06.031 |
| PII | S0021-9150(11)00553-3 |
| PMID | 21762915 |
| PMC | PMC3150192 |
| MeSH | ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters / genetics ATP-Binding Cassette Transporters / metabolism* Animals Cholesterol / metabolism Fluorobenzenes / pharmacology* Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology* Jurkat Cells Macrophages / drug effects* Macrophages / metabolism Mice Mice, Inbred C57BL Mice, Knockout Phagocytosis / drug effects* Pravastatin / pharmacology* Pyrimidines / pharmacology* RNA Interference RNA, Messenger / metabolism Rosuvastatin Calcium Simvastatin / pharmacology* Sulfonamides / pharmacology* Transfection Up-Regulation |
| IF | 3.919 |
| 引用数 | 26 |
| WOS 分野 | CARDIAC & CARDIOVASCULAR SYSTEMS PERIPHERAL VASCULAR DISEASE |
| 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 | 3 |
| 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 | Jurkat(RCB0806) J774 |