論文 - 詳細
| RRC ID | 39646 |
|---|---|
| 著者 | Kurosawa M, Numazawa S, Tani Y, Yoshida T. |
| タイトル | ERK signaling mediates the induction of inflammatory cytokines by bufalin in human monocytic cells. |
| ジャーナル | Am J Physiol Cell Physiol |
| Abstract |
Treatment of human leukemia THP-1 cells with bufalin, a specific inhibitor of Na(+)-K(+)-ATPase, sequentially induces c-fos and inflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) gene expressions before the appearance of mature phenotypes of monocytic cells. In this study we examined the signal transduction leading to bufalin-induced gene expressions. Bufalin selectively activated extracellular signal-regulated kinase (ERK), compared with other mitogen-activated protein (MAP) kinase family members. Pretreatment of THP-1 cells with PD-98059, an inhibitor of the ERK-kinase cascade, abolished bufalin-induced c-fos and IL-1 beta gene expressions, indicating that the ERK-kinase cascade mediates the induction of inflammatory cytokines by bufalin. Inhibition of the Na(+)/Ca(2+) exchanger by KB-R7943 and of protein kinase C (PKC) by Ro-31-8220 suppressed ERK activation and gene expressions of c-fos and IL-1 beta. These findings suggest that Na(+)-K(+)-ATPase inhibition by bufalin induces calcium influx and thereby activates PKC and ERK. In cells treated with an inhibitor of p38 MAP kinases, SB-203580, bufalin-mediated ERK activation became persistent and the induction of IL-1 beta and TNF-alpha expressions was significantly augmented. These results suggest that cross talk in bufalin-mediated ERK activation is negatively regulated by endogenous p38 MAP kinase activations. |
| 巻・号 | 278(3) |
| ページ | C500-8 |
| 公開日 | 2000-3-1 |
| DOI | 10.1152/ajpcell.2000.278.3.C500 |
| PMID | 10712238 |
| MeSH | Bufanolides / pharmacology* Cytokines / genetics* Enzyme Inhibitors / pharmacology* Gene Expression Regulation / drug effects Gene Expression Regulation / physiology* Genes, fos Humans Indoles / pharmacology Interleukin-1 / genetics Mitogen-Activated Protein Kinases / metabolism* Monocytes / physiology Protein Kinase C / antagonists & inhibitors Signal Transduction / drug effects Signal Transduction / physiology* Sodium-Calcium Exchanger / antagonists & inhibitors Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors Thiourea / analogs & derivatives Thiourea / pharmacology Tumor Cells, Cultured Tumor Necrosis Factor-alpha / genetics |
| IF | 3.485 |
| 引用数 | 35 |
| WOS 分野 | PHYSIOLOGY CELL BIOLOGY |
| 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 | THP-1(RCB1189) |