A glucogalactomanan polysaccharide isolated from Agaricus bisporus causes an inflammatory response via the ERK/MAPK and IκB/NFκB pathways in macrophages

Int J Biol Macromol. 2020 May 15:151:1067-1073. doi: 10.1016/j.ijbiomac.2019.10.148. Epub 2019 Nov 15.

Abstract

In the present study, a glucogalactomanan polysaccharide isolated from Agaricus bisporus named as TJ3 was investigated its immunomodulatory effects and molecular mechanisms in RAW 264.7 cells. Functional analysis showed TJ3 could inhibit the proliferation of RAW 264.7 cells in a certain concentration range. Moreover, TJ3 treatment increased the expression of inducible nitric oxide synthase (iNOS), which was responsible for increasing nitric oxide (NO) production. TJ3 also increased the expression of cyclooxygenase-2 (COX-2) and the mRNA levels of interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and COX-2 in RAW 264.7 cells. In addition, further elucidation of molecular mechanisms showed that ERK/MAPK and IκB/NFκB pathways were activated by TJ3 treatment via increased phosphorylation levels of ERK1/2 and IκB-α, respectively. These findings indicated that TJ3 had a huge promising immunostimulatory activity and its induced immune responses probably through stimulating the ERK/MAPK and IκB/NFκB pathways. Our results demonstrate that TJ3 may be used as a potent immune modulator.

Keywords: Agaricus bisporus polysaccharide; ERK; Immunoregulation; MAPK and IκB; NFκB pathways.

MeSH terms

  • Agaricus / chemistry*
  • Animals
  • Biomarkers
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / metabolism
  • Extracellular Signal-Regulated MAP Kinases
  • Fungal Polysaccharides / adverse effects*
  • Fungal Polysaccharides / chemistry
  • Galactose / analogs & derivatives
  • I-kappa B Proteins / metabolism
  • Immunomodulation / drug effects
  • Inflammation / etiology
  • Inflammation / metabolism*
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Mannans / adverse effects*
  • Mannans / chemistry
  • Mice
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • RAW 264.7 Cells
  • Signal Transduction / drug effects*

Substances

  • Biomarkers
  • Fungal Polysaccharides
  • I-kappa B Proteins
  • Mannans
  • NF-kappa B
  • galactomannan
  • Nitric Oxide
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Extracellular Signal-Regulated MAP Kinases
  • Galactose

Supplementary concepts

  • Agaricus bisporus