Hypoxia-induced changes in tight junction permeability of brain capillary endothelial cells are associated with IL-1beta and nitric oxide

• Published in: Neurobiology of disease Vol. 17; no. 3; pp. 491 - 499
• Main Authors: Yamagata, Kazuo, Tagami, Motoki, Takenaga, Fumio, Yamori, Yukio, Itoh, Shingo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2004; Elsevier
• Subjects: Animals; Brain - blood supply; Capillaries - physiology; Capillary endothelial cells; Cell Hypoxia - physiology; Cell Membrane Permeability - physiology; Cells, Cultured; Cerebrovascular Circulation - physiology; Electrophysiology - methods; Endothelium, Vascular - physiology; Extracellular Space - physiology; Hypoxia; IL-1; Interleukin-1 - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - analysis; Nitric Oxide - physiology; Occludin; Polymerase Chain Reaction; Swine; Tight junction; Tight Junctions - drug effects; Tight Junctions - physiology; Hypoxia; Tight junction; Capillary endothelial cells; IL-1; Nitric oxide; Occludin
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2004.08.001

We examined whether hypoxia alone could produce changes in the permeability of brain capillary endothelial cells (EC) and whether a stimulation of hypoxic status alters the gene expression of occludin and glucose transporter 1 (GLUT1). Exposure of EC to hypoxia resulted in increased permeability, with the greatest decrease in transendothelial electrical resistance (TER) at 40 h. Moreover, hypoxia alone induced the expression of both mRNA in EC. Furthermore, we found that interleukin-1 (IL-1)beta, glutamate, hydrogen peroxide (H
2O
2), and sodium nitroprusside (SNP) induced the expression of mRNA for occludin and GULT1 under normoxic condition. The decrease in TER due to hypoxia was inhibited on addition of an anti-IL1 antibody and nitric oxide synthase (NOS) inhibitor in EC. These results indicate that the expression of occludin and GLUT1 mRNA is sensitive to exposure to hypoxia and that the changes of permeability in EC are associated with IL-1beta and NO.