Suppressive effects of three diketopiperazines from marine-derived bacteria on TGFBIp-mediated septic responses in human endothelial cells and mice.

Abstract

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.

• Authors: Byeongjin Jung, Sae-Kwang Ku, Ming Gao, Kyung-Min Kim, Min-Su Han, Hyukjae Choi, Jong-Sup Bae
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 39 Issue 6 Pg. 843-54 (Jun 2016) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 27106029 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Diketopiperazines
• Extracellular Matrix Proteins
• Transforming Growth Factor beta
• betaIG-H3 protein

Topics

• Animals
• Anti-Inflammatory Agents (isolation & purification, pharmacology)
• Bacillus (isolation & purification, metabolism)
• Cell Survival (drug effects, immunology)
• Diketopiperazines (isolation & purification, pharmacology)
• Endothelial Cells (drug effects, immunology)
• Extracellular Matrix Proteins (antagonists & inhibitors, immunology)
• Geologic Sediments (microbiology)
• Human Umbilical Vein Endothelial Cells
• Male
• Mice, Inbred C57BL
• Micrococcaceae (isolation & purification, metabolism)
• Molecular Structure
• Porifera (microbiology)
• Sepsis (drug therapy, immunology)
• Transforming Growth Factor beta (antagonists & inhibitors, immunology)