• Byeongjin Jung, Sae-Kwang Ku, and Jong-Sup Bae.
• College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 Republic of Korea.
• Biochem. Biophys. Res. Commun. 2015 Aug 7;463(4):661-6.

AbstractThe 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.Copyright © 2015 Elsevier Inc. All rights reserved.

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