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Updated: Jun 26, 2025
Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Published on: May 2, 2018
Mexenone protects mice from LPS-induced sepsis by EC barrier stabilization
Yoon Ji Choi1, Jimin An2, Ji Hye Kim2
1In Vivo Research Center (IVRC), UCRF, UNIST, Ulsan, Korea.
Abstract:
Blood vessels permit the selective passage of molecules and immune cells between tissues and circulation. Uncontrolled inflammatory responses from an infection can increase vascular permeability and edema, which can occasionally lead to fatal organ failure. We identified mexenone as a vascular permeability blocker by testing 2,910 compounds in the Clinically Applied Compound Library using the lipopolysaccharide (LPS)-induced vascular permeability assay. Mexenone suppressed the LPS-induced downregulation of junctional proteins and phosphorylation of VE-cadherin in Bovine Aortic Endothelial Cells (BAECs). The injection of mexenone 1 hr before LPS administration completely blocked LPS-induced lung vascular permeability and acute lung injury in mice after 18hr. Our results suggest that mexenone-induced endothelial cell (EC) barrier stabilization could be effective in treating sepsis patients.
Insights
Mexenone blocks increased vascular permeability and lung injury caused by inflammation. This compound stabilizes the endothelial cell barrier, offering potential treatment for sepsis patients.
Area of Science:
- Vascular biology
- Inflammation research
- Drug discovery
Background:
- Increased vascular permeability during inflammation can lead to edema and organ failure.
- Sepsis involves uncontrolled inflammatory responses that compromise the integrity of blood vessels.
Purpose of the Study:
- To identify compounds that can block vascular permeability.
- To evaluate the therapeutic potential of mexenone in models of sepsis-induced lung injury.
Main Methods:
- Screened 2,910 compounds using a lipopolysaccharide (LPS)-induced vascular permeability assay.
- Assessed mexenone's effects on junctional proteins and VE-cadherin phosphorylation in bovine aortic endothelial cells (BAECs).
- Evaluated mexenone's efficacy in preventing LPS-induced lung vascular permeability and acute lung injury in mice.
Main Results:
- Mexenone was identified as a potent blocker of vascular permeability.
- Mexenone prevented the LPS-induced suppression of junctional proteins and VE-cadherin phosphorylation in BAECs.
- Pre-treatment with mexenone completely inhibited LPS-induced lung vascular permeability and acute lung injury in mice.
Conclusions:
- Mexenone effectively stabilizes the endothelial cell barrier.
- Mexenone demonstrates therapeutic potential for treating sepsis-associated vascular dysfunction and acute lung injury.
