Search

Transforming growth factor β induced protein (TGFBIp) is an extracellular matrix protein which expression in several cell types is greatly increased by TGF-β. TGFBIp is released by human umbilical vein endothelial cells (HUVECs), and functions as a mediator of experimental sepsis. Pentacyclic triterpenoids bearing a carboxyl group at C-27 position, 3β,6α-dihydroxyolup-20(29)-ene ( 1 ), 3β,6β-dihydroxyolean-12-en-27-oic acid ( 2 ) and 3β,24-dihydroxyolean-12-en-27-oic acid ( 3 ), are representative bioactive molecules in the genus Astilbe that possess cytotoxic, anti-inflammatory and wounds healing activities. Based on the biological effects of C-27 carboxylated pentacyclic triterpenoids, we investigated the anti-inflammatory effects of compounds 1–3 against TGFBIp-mediated vascular inflammatory responses. The anti-inflammatory activities of compounds 1–3 were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated human HUVECs and mice. We found that compounds 1–3 inhibited TGFBIp-induced barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of neutrophils to human endothelial cells. Each compound also suppressed TGFBIp-induced hyperpermeability and leukocyte migration in vivo . These results suggest that compounds 1–3 possess anti-inflammatory functions by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. 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 (HUVECs), and functions as a mediator of experimental sepsis. Here, we investigated the anti-septic effects and underlying mechanisms of methylthiouracil (MTU), used as antithyroid drug, against TGFBIp-mediated septic responses in HUVECs and mice. The anti-inflammatory activities of MTU were determined by measuring permeability, human neutrophils adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated HUVECs and mice. According to the results, MTU effectively inhibited lipopolysaccharide-induced release of TGFBIp, and suppressed TGFBIp-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, MTU suppressed CLP-induced sepsis lethality and pulmonary injury. Collectively, these results indicate that MTU could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the TGFBIp signaling pathway. [ABSTRACT FROM AUTHOR]