Stimulation of macrophages with the β-glucan produced by aureobasidium pullulans promotes the secretion of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)

PLoS One. 2015 Apr 13;10(4):e0124809. doi: 10.1371/journal.pone.0124809. eCollection 2015.

Abstract

A β-glucan produced by Aureobasidium pullulans (AP-PG) is consisting of a β-(1,3)-linked main chain with β-(1,6)-linked glucose side residues. Various β-glucans consisting of β-(1,3)-linked main chain including AP-PG are believed to exhibit anti-tumor activities, and actually, anti-tumor activities of AP-PG in mice have been demonstrated. In this study, we demonstrate that stimulation with AP-PG induces TRAIL expression in mouse and human macrophage-like cell lines. TRAIL is known to be a cytokine which specifically induces apoptosis in transformed cells, but not in untransformed cells. The expression of TRAIL mRNA after stimulation with AP-PG was increased in RAW264.7 cells, Mono Mac 6 cells, and macrophage-differentiated THP-1 cells. The mRNA expression of TNF-α and FasL is only weakly increased after stimulation with AP-PG. The induction activity of TRAIL by curdlan, a bacterial β-glucan, was very similar to that by AP-PG in RAW264.7 cells, but weaker in macrophage-differentiated THP-1 cells. Activation of caspases was found in HeLa cells after treatment with the supernatant of cultured medium from AP-PG-stimulated Mono Mac 6 cells, and was inhibited by the anti-TRAIL neutralizing antibody. These findings suggest that the stimulation with AP-PG effectively induces TRAIL in macrophages, and that it may be related to apoptosis induction of tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Ascomycota / growth & development
  • Ascomycota / metabolism*
  • Caspases / metabolism
  • Cells, Cultured
  • Humans
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • Polysaccharides, Bacterial / pharmacology*
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • beta-Glucans / pharmacology*

Substances

  • Polysaccharides, Bacterial
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha
  • beta-Glucans
  • curdlan
  • Caspases

Grant support

This study was funded by by Aureo Co., Ltd., and Aureo-Science Co., Ltd. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.