Carboxylic and O-acetyl moieties are essential for the immunostimulatory activity of glucuronoxylomannan: a novel TLR4 specific immunostimulator from Auricularia auricula-judae

Chem Commun (Camb). 2018 Jun 21;54(51):6995-6998. doi: 10.1039/c7cc09927d.

Abstract

This study established the comprehensive repeating unit structure of immunologically active glucuronoxylomannan (AAPS) from wood ear mushroom, Auricularia auricula-judae. We identified Toll-like receptor 4 (TLR4) as a critical receptor involved in AAPS-induced macrophage activation to secrete pro-inflammatory cytokines. Molecular modeling data and chemical modifications of AAPS revealed that both carboxylic and acetyl moieties of AAPS are equally essential in TLR4 binding to exert in vitro immunostimulatory activity.

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / isolation & purification
  • Adjuvants, Immunologic / pharmacology*
  • Agaricales / chemistry*
  • Animals
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Mice, Knockout
  • Polysaccharides / chemistry
  • Polysaccharides / immunology*
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology*
  • RAW 264.7 Cells
  • Structure-Activity Relationship
  • Toll-Like Receptor 4 / agonists*
  • Toll-Like Receptor 4 / immunology*
  • Toll-Like Receptor 4 / metabolism

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Lipopolysaccharides
  • Polysaccharides
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • glucuronoxylomannan