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

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.