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

Joen Rong Sheu, Zhih Cherng Chen, Ming Jen Hsu, Shwu Huey Wang, Kuo Wei Jung, Wei Fan Wu, Szu Han Pan, Ruei Dun Teng, Chih Hao Yang, Cheng Ying Hsieh

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 IκBα 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; IκBα 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.

Original languageEnglish
Pages (from-to)999-1013
Number of pages15
JournalJournal of Cellular and Molecular Medicine
Volume22
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

Fingerprint

Protein Phosphatase 2
Ceramides
Nitric Oxide Synthase Type II
Polysaccharides
Lipopolysaccharides
Macrophages
Reactive Oxygen Species
Mitogen-Activated Protein Kinases
Phosphorylation
JNK Mitogen-Activated Protein Kinases
Mycelium
Extracellular Signal-Regulated MAP Kinases
Peritoneal Macrophages
Hydroxyl Radical
Nitric Oxide
Anti-Inflammatory Agents
Up-Regulation
RAW 264.7 Cells
Water

Keywords

  • ceramide
  • CME-1
  • immunomodulatory property
  • protein phosphatase 2A
  • reactive oxygen species

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

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

In: Journal of Cellular and Molecular Medicine, Vol. 22, No. 2, 01.02.2018, p. 999-1013.

Research output: Contribution to journalArticle

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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 IκBα 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; IκBα 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.",
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AU - Chen, Zhih Cherng

AU - Hsu, Ming Jen

AU - Wang, Shwu Huey

AU - Jung, Kuo Wei

AU - Wu, Wei Fan

AU - Pan, Szu Han

AU - Teng, Ruei Dun

AU - Yang, Chih Hao

AU - Hsieh, Cheng Ying

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