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 language | English |
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Pages (from-to) | 387-398 |
Number of pages | 12 |
Journal | Journal of Natural Medicines |
Volume | 74 |
Issue number | 2 |
DOIs | |
State | Published - 1 Mar 2020 |
Keywords
- Collismycin C
- HUVEC
- Sepsis
- Severe inflammation
- Tgfbip