Mechanism of the anti-inflammatory activity by a polysaccharide from Dictyophora indusiata in lipopolysaccharide-stimulated macrophages

Int J Biol Macromol. 2019 Apr 1:126:1158-1166. doi: 10.1016/j.ijbiomac.2019.01.022. Epub 2019 Jan 6.

Abstract

Dictyophora indusiata polysaccharides (DIP) shows antioxidant, anti-tumor and immunostimulatory activities. However, the anti-inflammatory roles of DIP in NLRP3 inflammasome in LPS-stimulated macrophages are still not well defined. In this study, we investigated the mechanism of the anti-inflammatory activity of DIP in LPS-primed RAW264.7 macrophages. Our data showed that DIP inhibited NF-κB signal pathway via modulating TLR4 expression, phosphorylation of IκBα and nuclear translocation of NF-κB-p65 subunit. Meanwhile, DIP reduced inflammasome activation via decreasing NLRP3 expression in cytoplasmic pools, limiting self-assembly of NLRP3 inflammasome, as well as the subsequent activation of caspase-1 and the secretion of IL-1β and IL-18. For the first time, we show that the anti-inflammatory activity of DIP is mediated by inhibiting TLR4/NF-κB signal pathway and NLRP3 inflammasome activation during LPS-induced acute inflammation in RAW264.7 macrophages.

Keywords: Anti-inflammatory activity; Dictyophora indusiata polysaccharide; NLRP3 inflammasome.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Basidiomycota / chemistry*
  • Inflammasomes / metabolism
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / pharmacology
  • Lipopolysaccharides / therapeutic use*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics

Substances

  • Anti-Inflammatory Agents
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • Lipopolysaccharides
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Reactive Oxygen Species
  • Toll-Like Receptor 4