論文 - 詳細
| RRC ID | 44264 |
|---|---|
| 著者 | Hirano S, Kataoka T. |
| タイトル | Deoxynivalenol induces ectodomain shedding of TNF receptor 1 and thereby inhibits the TNF-α-induced NF-κB signaling pathway. |
| ジャーナル | Eur J Pharmacol |
| Abstract |
Trichothecene mycotoxins are known to inhibit eukaryotic translation and to trigger the ribotoxic stress response, which regulates gene expression via the activation of the mitogen-activated protein (MAP) kinase superfamily. In this study, we found that deoxynivalenol induced the ectodomain shedding of tumor necrosis factor (TNF) receptor 1 (TNFRSF1A) and thereby inhibited the TNF-α-induced signaling pathway. In human lung carcinoma A549 cells, deoxynivalenol and 3-acetyldeoxynivalenol inhibited the expression of intercellular adhesion molecule-1 (ICAM-1) induced by TNF-α more strongly than that induced by interleukin 1α (IL-1α), whereas T-2 toxin and verrucarin A exerted nonselective inhibitory effects. Deoxynivalenol and 3-acetyldeoxynivalenol also inhibited the nuclear factor κB (NF-κB) signaling pathway induced by TNF-α, but not that induced by IL-1α. Consistent with these findings, deoxynivalenol and 3-acetyldeoxynivalenol induced the ectodomain shedding of TNF receptor 1 by TNF-α-converting enzyme (TACE), also known as a disintegrin and metalloproteinase 17 (ADAM17). In addition to the TACE inhibitor TAPI-2, the MAP kinase or extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126 and the p38 MAP kinase inhibitor SB203580, but not the c-Jun N-terminal kinase (JNK) inhibitor SP600125, suppressed the ectodomain shedding of TNF receptor 1 induced by deoxynivalenol and reversed its selective inhibition of TNF-α-induced ICAM-1 expression. Our results demonstrate that deoxynivalenol induces the TACE-dependent ectodomain shedding of TNF receptor 1 via the activation of ERK and p38 MAP kinase, and thereby inhibits the TNF-α-induced NF-κB signaling pathway. |
| 巻・号 | 701(1-3) |
| ページ | 144-51 |
| 公開日 | 2013-2-15 |
| DOI | 10.1016/j.ejphar.2013.01.019 |
| PII | S0014-2999(13)00026-5 |
| PMID | 23357557 |
| MeSH | Cell Line, Tumor Extracellular Signal-Regulated MAP Kinases / metabolism Gene Expression Regulation / drug effects Humans Intercellular Adhesion Molecule-1 / metabolism Interleukin-1alpha / pharmacology Mycotoxins / toxicity NF-kappa B / metabolism* Protein Structure, Tertiary Receptors, Tumor Necrosis Factor / chemistry* Receptors, Tumor Necrosis Factor / metabolism* Signal Transduction / drug effects* Trichothecenes / pharmacology* Trichothecenes / toxicity Tumor Necrosis Factor-alpha / pharmacology* p38 Mitogen-Activated Protein Kinases / metabolism |
| IF | 3.263 |
| 引用数 | 15 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2(RCB1648) |