title: Suppressive effects of polyozellin on TGFBIp-mediated septic responses in human endothelial cells and mice.
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.
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Byeongjin
authors.initials: B
authors.lastname: Jung
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Yang
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: baejs@knu.ac.kr.
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002432:Cecum; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011677:Punctures; D018805:Sepsis / Q000209:etiology / Q000517:prevention & control*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000099222:betaIG-H3 Protein
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016326:Extracellular Matrix Proteins; D005663:Furans; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C109015:polyozellin
keywords: Mice; Polyozellin; Sepsis; Severe inflammation; TGFBIp