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KMID : 0043320160390060843
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Archives of Pharmacal Research
2016 Volume.39 No. 6 p.843 ~ p.854
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Suppressive effects of three diketopiperazines from marine-derived bacteria on TGFBIp-mediated septic responses in human endothelial cells and mice
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Jung Byeong-Jin
Ku Sae-Kwang
Gao Ming
Kim Kyung-Min
Han Min-Su
Choi Hyuk-Jae
Bae Jong-Sup
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Abstract
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Diketopiperazine is a naturally occurring cyclic dipeptide found from diverse living organisms. The compounds in this structure class have been known with a broad spectrum of bioactivities including anti-inflammatory activities. 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. Here, three (1?3) of diketopiperazines were isolated from two strains of marine-derived bacteria and we hypothesized that 1?3 could reduce TGFBIp-mediated severe inflammatory responses in human endothelial cells and mice. Here, we investigated the anti-septic effects and underlying mechanisms of 1?3 against TGFBIp-mediated septic responses. 1?3 effectively inhibited lipopolysaccharide-induced release of TGFBIp and suppressed TGFBIp-mediated septic responses. In addition, 1?3 suppressed cecal ligation and puncture (CLP)-induced sepsis lethality and pulmonary injury. In conclusion, 1?3 suppressed TGFBIp-mediated and CLP-induced septic responses. Therefore, 1?3 could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the TGFBIp signaling pathway.
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KEYWORD
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Diketopiperazine, TGFBIp, Sepsis, Severe inflammation, Mice
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