Suppressive functions of collismycin C in TGFBIp-mediated septic responses

Bong Seon Lee, Eonmi Kim, Hyukjae Choi, Jong Sup Bae

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein; its expression by several cell types is greatly increased by TGF-β. TGFBIp is released by primary human umbilical vein endothelial cells (HUVECs) and functions as a mediator of experimental sepsis. 2,2′-Bipyridine-containing natural products are generally accepted to have antimicrobial, cytotoxic and anti-inflammatory properties. We hypothesized that a 2,2′-bipyridine containing natural product, collismycin C, could reduce TGFBIp-mediated severe inflammatory responses in human endothelial cells and mice. Here we investigated the effects and underlying mechanisms of collismycin C against TGFBIp-mediated septic responses. Collismycin C effectively inhibited lipopolysaccharide-induced release of TGFBIp and suppressed TGFBIp-mediated septic responses. In addition, collismycin C suppressed TGFBIp-induced sepsis lethality and pulmonary injury. This suppression of TGFBIp-mediated and CLP-induced septic responses indicates that collismycin C is a potential therapeutic agent for various severe vascular inflammatory diseases, with inhibition of the TGFBIp signaling pathway as the mechanism of action.

Original languageEnglish
Pages (from-to)387-398
Number of pages12
JournalJournal of Natural Medicines
Volume74
Issue number2
DOIs
StatePublished - 1 Mar 2020

Keywords

  • Collismycin C
  • HUVEC
  • Sepsis
  • Severe inflammation
  • Tgfbip

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