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| 標題: | CME-1, a novel polysaccharide, suppresses iNOS expression in lipopolysaccharide-stimulated macrophages through ceramide-initiated protein phosphatase 2A activation |
| 作者: | Sheu, Joen-Rong
Chen, Zhih-Cherng
Hsu, Ming-Jen
Wang, Shwu-Huey
Jung, Kuo-Wei
Wu, Wei-Fan
Pan, Szu-Han
Teng, Ruei-Dun
Yang, Chih-Hao
Hsieh, Cheng-Ying |
| 關鍵字: | CME-1
immunomodulatory property
protein phosphatase 2A
ceramide
reactive oxygen species |
| 日期: | 2018-02 |
| 上傳時間: | 2019-11-15 15:48:37 (UTC+8) |
| 出版者: | WILEY |
| 摘要: | CME-1, a novel water-soluble polysaccharide purified from Ophiocordyceps sinensis mycelia, has anti-oxidative, antithrombotic and antitumour properties. In this study, other major attributes of CME-1, namely anti-inflammatory and immunomodulatory properties, were investigated. Treating lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with CME-1 concentration-dependently suppressed nitric oxide formation and inducible nitric oxide synthase (iNOS) expression. In the CME-1-treated RAW 264.7 cells, LPS-induced I kappa B alpha degradation and the phosphorylation of p65, Akt and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38, were reduced. Treatment with a protein phosphatase 2A (PP2A)-specific inhibitor, significantly reversed the CME-1-suppressed iNOS expression; I kappa B alpha degradation; and p65, Akt and MAPK phosphorylation. PP2A activity up-regulation and PP2A demethylation reduction were also observed in the cells. Moreover, CME-1-induced PP2A activation and its subsequent suppression of LPS-activated RAW 264.7 cells were diminished by the inhibition of ceramide signals. LPS-induced reactive oxygen species (ROS) and hydroxyl radical formation were eliminated by treating RAW 264.7 cells with CME-1. Furthermore, the role of ceramide signalling pathway and anti-oxidative property were also demonstrated in CME-1-mediated inhibition of LPS-activated primary peritoneal macrophages. In conclusion, CME-1 suppressed iNOS expression by up-regulating ceramide-induced PP2A activation and reducing ROS production in LPS-stimulated macrophages. CME-1 is a potential therapeutic agent for treating inflammatory diseases. |
| link: | http://dx.doi.org/10.1111/jcmm.13424 |
| 關聯: | Journal of Cellular Physiology, v.22, n.2, pp.999-1013 |
| 顯示於類別: | [藥學系(所)] 期刊論文
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| 10.1111-jcmm.13424.pdf | | 1304Kb | Adobe PDF | 409 | 檢視/開啟 | | index.html | | 0Kb | HTML | 1743 | 檢視/開啟 |
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