論文 - 詳細
| RRC ID | 3854 |
|---|---|
| 著者 | Uto T, Fujii M, Hou DX. |
| タイトル | Inhibition of lipopolysaccharide-induced cyclooxygenase-2 transcription by 6-(methylsulfinyl) hexyl isothiocyanate, a chemopreventive compound from Wasabia japonica (Miq.) Matsumura, in mouse macrophages. |
| ジャーナル | Biochem Pharmacol |
| Abstract |
6-(Methylsulfinyl)hexyl isothiocyanate (6-MITC) is a chemopreventive compound occurring in Wasabi (Wasabia japonica (Miq.) Matsumura), which is a very popular pungent spice in Japan. We investigated the effects of 6-MITC on the expression of cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-activated murine macrophage RAW264 cells. Treatment with 6-MITC suppressed LPS-mediated induction of COX-2 protein in a dose-dependent manner. Transfections with various COX-2 promoter reporter constructs revealed that the inhibitory effects of 6-MITC on COX-2 gene expression were directed by the core promoter elements including nuclear factor kappaB (NF-kappaB), CCAAT/enhancer-binding protein (C/EBP) and cyclic AMP-response element (CRE) sites. Western blotting analysis showed that 6-MITC inhibited LPS-induced activation of MAPK (ERK, p38 kinase and JNK) and transcriptional factors (CREB, c-Jun and C/EBPdelta) binding the core elements of COX-2 promoter, substantiating the involvement of these signal transduction pathways in the regulation of COX-2 expression by 6-MITC. Moreover, Western blotting experiments with MAPK-specific inhibitors (U0126 for MEK1/2, SB203580 for p38 kinase and SP600125 for JNK) demonstrated that 6-MITC suppressed LPS-induced COX-2 expression by blocking the activation of JNK-mediated AP-1 and ERK/p38 kinase-mediated CREB or C/EBPdelta. Finally, the structure-activity study revealed that the inhibitory potency of methylsulfinyl isothiocyanates (MITCs) depended on the methyl chain length. These findings demonstrate for the first time that 6-MITC is an effective agent to attenuate COX-2 production, and enhance our understanding of the anti-inflammation properties of 6-MITC. |
| 巻・号 | 70(12) |
| ページ | 1772-84 |
| 公開日 | 2005-12-5 |
| DOI | 10.1016/j.bcp.2005.09.023 |
| PII | S0006-2952(05)00629-5 |
| PMID | 16256955 |
| MeSH | Animals Anti-Inflammatory Agents / pharmacology* CCAAT-Enhancer-Binding Protein-delta / metabolism Cell Line Cyclic AMP Response Element-Binding Protein / metabolism Cyclooxygenase 2 / genetics* Dinoprostone / metabolism Isothiocyanates / pharmacology* Lipopolysaccharides / pharmacology* MAP Kinase Signaling System Macrophages / drug effects Macrophages / enzymology Mice Phosphorylation Structure-Activity Relationship Transcription, Genetic / drug effects |
| IF | 4.96 |
| 引用数 | 41 |
| 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 | RAW 264(RCB0535) |