Mexenone protects mice from LPS-induced sepsis by EC barrier stabilization.
Yoon Ji ChoiJimin AnJi Hye KimSa Bin LeeBo Seok LeeChae Young EomHyohi LeeNayeong KwonIl Shin KimKyoung-Su ParkSooah ParkJung-Woog ShinSanguk YunPublished in: PloS one (2024)
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.
Keyphrases
- lps induced
- endothelial cells
- inflammatory response
- high glucose
- lipopolysaccharide induced
- end stage renal disease
- intensive care unit
- toll like receptor
- gene expression
- acute kidney injury
- high fat diet induced
- newly diagnosed
- heart failure
- vascular endothelial growth factor
- left ventricular
- cell proliferation
- peritoneal dialysis
- signaling pathway
- high throughput
- type diabetes
- coronary artery
- atrial fibrillation
- ultrasound guided
- anti inflammatory
- pulmonary hypertension
- patient reported outcomes