Polysaccharide from Ganoderma atrum induces tumor necrosis factor-α secretion via phosphoinositide 3-kinase/Akt, mitogen-activated protein kinase and nuclear factor-κB signaling pathways in RAW264.7 cells

Int Immunopharmacol. 2012 Dec;14(4):362-8. doi: 10.1016/j.intimp.2012.09.005. Epub 2012 Sep 23.

Abstract

The aim of this study was to investigate the signaling pathways involved in the macrophage activation by Ganoderma atrum polysaccharide (PSG-1) and elucidate the molecular mechanism of PSG-1-induced signal transduction in the regulation of tumor necrosis factor (TNF)-α secretion. Our results illustrated that the mitogen-activated protein kinase (MAPK) pathways were simultaneously activated and involved in PSG-1-induced TNF-α secretion in RAW264.7 cells. Moreover, our results also demonstrated that the phosphoinositide 3-kinase (PI3K)/Akt pathway was stimulated and played an important role in the PSG-1 induced TNF-α secretion. Additionally, the present study showed that nuclear factor (NF)-κB activation by PSG-1 was triggered by PI3K/Akt/MAPK pathway and NF-κB participated in PSG-1 stimulated TNF-α production. In conclusion, we have elucidated the mechanism of PSG-1-mediated immunomodulatory activities, and provide a theoretical basis for the potential of PSG-1 as a novel immunomodulating agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Ganoderma / chemistry*
  • Gene Expression Regulation / drug effects
  • Macrophages / drug effects*
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Polysaccharides / chemistry
  • Polysaccharides / pharmacology*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • NF-kappa B
  • Polysaccharides
  • Tumor Necrosis Factor-alpha
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase Kinases