Open AccessBrefeldin A and kifunensine modulate LPS-induced lung endothelial hyperpermeability in human and bovine cells
Author(s) -
KhadejaTul Kubra,
Nektarios Barabutis
Publication year - 2021
Publication title -
american journal of physiology. cell physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.432
H-Index - 181
eISSN - 1522-1563
pISSN - 0363-6143
DOI - 10.1152/ajpcell.00142.2021
Subject(s) - brefeldin a , ards , unfolded protein response , microbiology and biotechnology , inducer , lung , acute respiratory distress , in vitro , endothelial stem cell , sepsis , immunology , biology , chemistry , medicine , endoplasmic reticulum , biochemistry , gene , golgi apparatus
Endothelial hyperpermeability is the hallmark of acute respiratory distress syndrome (ARDS). Laborious efforts in the investigation of the molecular pathways involved in the regulation of the vascular barrier shall reveal novel therapeutic targets toward that respiratory disorder. Herein, we investigate in vitro the effects of the α-1,2-mannosidase 1 inhibitor kifunensine (KIF) and brefeldin A (BFA) in the lipopolysaccharides (LPS)-induced endothelial breakdown. Our results suggest that BFA opposes the deteriorating effects of KIF [unfolded protein response (UPR) suppressor] toward the lung microvasculature. Since KIF is a UPR suppressor, and brefeldin A is a UPR inducer, we suggest that a carefully devised UPR manipulation may deliver novel therapeutic avenues in diseases related to endothelial barrier dysfunction (e.g., ARDS and sepsis).