Suppressive effects of polyozellin on TGFBIp-mediated septic responses in human endothelial cells and mice

Nutr Res. 2016 Apr;36(4):380-389. doi: 10.1016/j.nutres.2015.12.009. Epub 2015 Dec 18.

Abstract

Polyozellus multiplex (Thelephoraceae) is a wild mushroom in Korea and Japan and is usually harvested in early autumn for food. Polyozellin, a major constituent of the edible mushroom P multiplex, has been known to exhibit biological activities such as antioxidative and anti-inflammatory effects. Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein whose expression in several cell types is greatly increased by TGF-β. TGFBIp is released by human umbilical vein endothelial cells and functions as a mediator of experimental sepsis. We hypothesized that polyozellin could reduce TGFBIp-mediated severe inflammatory responses in human endothelial cells and mice. Here, we investigated the antiseptic effects and underlying mechanisms of polyozellin against TGFBIp-mediated septic responses. Polyozellin effectively inhibited lipopolysaccharide-induced release of TGFBIp and suppressed TGFBIp-mediated septic responses. In addition, polyozellin suppressed cecal ligation and puncture-induced sepsis lethality and pulmonary injury. In conclusion, polyozellin suppressed TGFBIp-mediated and cecal ligation and puncture-induced septic responses. Therefore, polyozellin could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the TGFBIp signaling pathway.

Keywords: Mice; Polyozellin; Sepsis; Severe inflammation; TGFBIp.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents
  • Antioxidants
  • Cecum
  • Cells, Cultured
  • Endothelial Cells / drug effects*
  • Endothelial Cells / physiology
  • Extracellular Matrix Proteins / analysis
  • Extracellular Matrix Proteins / antagonists & inhibitors
  • Extracellular Matrix Proteins / pharmacology*
  • Furans / pharmacology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Ligation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Punctures
  • Sepsis / etiology
  • Sepsis / prevention & control*
  • Signal Transduction
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Extracellular Matrix Proteins
  • Furans
  • Transforming Growth Factor beta
  • polyozellin
  • betaIG-H3 protein