論文 - 詳細
| RRC ID | 56111 |
|---|---|
| 著者 | Sakamoto T, Ohashi W, Tomita K, Hattori K, Matsuda N, Hattori Y. |
| タイトル | Anti-inflammatory properties of cilostazol: Its interruption of DNA binding activity of NF-κB from the Toll-like receptor signaling pathways. |
| ジャーナル | Int Immunopharmacol |
| Abstract |
Cilostazol, a selective inhibitor of phosphodiesterase type III with anti-platelet, anti-mitogenic, and vasodilating properties, is widely used to treat ischemic symptoms of peripheral vascular disease. Ample evidence has suggested that cilostazol also exhibits an anti-inflammatory effect, but its anti-inflammatory mechanism is not fully understood. Here, we showed that cilostazol specifically inhibited expression of cytokines, which are induced by nuclear factor-κB (NF-κB) activation, in RAW264.7 macrophage cells stimulated with different Toll-like receptor (TLR) ligands. Cilostazol was found to significantly reduce TLR-4 and TLR-3 ligands-stimulated NF-κB transcriptional activity, which was quantified by luciferase reporter assays. However, cilostazol was without effect on IκBα degradation and NF-κB p65 phosphorylation and nuclear translocation after challenge with the TLR-4 ligand lipopolysaccharide (LPS). Cilostazol did not also prevent the LPS-induced increase in phosphorylated levels of the mitogen-activated protein kinase (MAPK) family. On the other hand, using chromatin immunoprecipitation assays, we demonstrated that cilostazol reduced the LPS-induced transcriptional activities of interleukin-6 and tumor necrosis factor-α by preventing the recruitment of NF-κB p65 to these gene promoters. When cilostazol was given to mice by oral gavage daily for 7 days, LPS-induced aberrant pro-inflammatory cytokine production and end-organ tissue injury were significantly reduced. The results of this study suggest that cilostazol is capable of directly interrupting DNA binding activity of NF-κB proteins from the TLR signaling pathways. The therapy to specifically intervene in this pathway may be potentially beneficial for the prevention of different inflammatory disorders. |
| 巻・号 | 62 |
| ページ | 120-131 |
| 公開日 | 2018-9-1 |
| DOI | 10.1016/j.intimp.2018.06.021 |
| PII | S1567-5769(18)30272-8 |
| PMID | 30005227 |
| MeSH | Animals Anti-Inflammatory Agents / pharmacology* Cilostazol / pharmacology* Cytokines / genetics DNA / metabolism* Mice NF-KappaB Inhibitor alpha / metabolism NF-kappa B / genetics NF-kappa B / metabolism* RAW 264.7 Cells Signal Transduction Toll-Like Receptors / metabolism* Transcription, Genetic / drug effects |
| IF | 3.361 |
| 引用数 | 6 |
| 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 | X(Twitter) |
| 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 | RAW 264(RCB0535) |