CME-1, a novel polysaccharide, suppresses iNOS expression in lipopolysaccharide-stimulated macrophages through ceramide-initiated protein phosphatase 2A activation

doi:10.1111/jcmm.13424

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Title:	CME-1, a novel polysaccharide, suppresses iNOS expression in lipopolysaccharide-stimulated macrophages through ceramide-initiated protein phosphatase 2A activation
Authors:	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
Keywords:	CME-1 immunomodulatory property protein phosphatase 2A ceramide reactive oxygen species
Date:	2018-02
Issue Date:	2019-11-15 15:48:37 (UTC+8)
Publisher:	WILEY
Abstract:	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.
???metadata.dc.relation.uri???:	http://dx.doi.org/10.1111/jcmm.13424
Relation:	Journal of Cellular Physiology, v.22, n.2, pp.999-1013
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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