Proteoglycan from Bacillus sp. BS11 Inhibits the Inflammatory Response by Suppressing the MAPK and NF-κB Pathways in Lipopolysaccharide-Induced RAW264.7 Macrophages

Mar Drugs. 2020 Nov 24;18(12):585. doi: 10.3390/md18120585.

Abstract

Inflammation is involved in the pathogenesis of many debilitating diseases. Proteoglycan isolated from marine Bacillus sp. BS11 (EPS11) was shown to have anticancer activity, but its anti-inflammatory potential remains elusive. In the present study, the anti-inflammatory effects and mechanism of EPS11 were evaluated using a lipopolysaccharide (LPS)-induced RAW264.7 macrophage model. Biochemical characterization showed that the total sugar content and protein content of EPS11 were 49.5% and 30.2% respectively. EPS11 was composed of mannose, glucosamine, galactosamine, glucose, galactose, rhamnose, and glucuronic acid. Its molecular weight was determined to be 3.06 × 105 Da. The protein determination of EPS11 was also performed. EPS11 displayed a strong anti-inflammatory effect on LPS-stimulated RAW264.7 macrophages in vitro, which significantly suppressed inflammatory cytokines and mediators (such as NO, TNF-α, IL-6 and IL-1β, and COX-2). Western blot analysis indicated that EPS11 could downregulate the expression of many key proteins in mitogen-activated protein kinases (MAPKs) and transcription factor nuclear factor-κB (NF-κB) signaling pathways. In particular, EPS11 almost completely inhibited the expression of NF-κB P65, which indicated that EPS11 acted primarily on the NF-κB pathways. These findings offer new insights into the molecular mechanism underlying the anti-inflammatory effect of EPS11.

Keywords: Bacillus sp.; anti-inflammation; macrophages; proteoglycan.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Bacillus / metabolism*
  • Cytokines / metabolism
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / toxicity
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Structure
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • Phosphorylation
  • Proteoglycans / isolation & purification
  • Proteoglycans / pharmacology*
  • RAW 264.7 Cells
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Proteoglycans
  • Nitric Oxide
  • Mitogen-Activated Protein Kinases