Mexenone protects mice from LPS-induced sepsis by EC barrier stabilization.

Autor: Choi YJ; In Vivo Research Center (IVRC), UCRF, UNIST, Ulsan, Korea., An J; Department of Biotechnology, Inje University, Gimhae, Korea., Kim JH; Department of Biotechnology, Inje University, Gimhae, Korea., Lee SB; Department of Biotechnology, Inje University, Gimhae, Korea., Lee BS; Department of Biotechnology, Inje University, Gimhae, Korea., Eom CY; Department of Biotechnology, Inje University, Gimhae, Korea., Lee H; Department of Biotechnology, Inje University, Gimhae, Korea., Kwon N; Department of Biotechnology, Inje University, Gimhae, Korea., Kim IS; In Vivo Research Center (IVRC), UCRF, UNIST, Ulsan, Korea., Park KS; In Vivo Research Center (IVRC), UCRF, UNIST, Ulsan, Korea., Park S; In Vivo Research Center (IVRC), UCRF, UNIST, Ulsan, Korea., Shin JW; Department of Biomedical Engineering, Inje University, Gimhae, Korea., Yun S; Department of Biotechnology, Inje University, Gimhae, Korea.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 May 09; Vol. 19 (5), pp. e0302628. Date of Electronic Publication: 2024 May 09 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0302628
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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