Changes in cytoskeletal and tight junctional proteins correlate with decreased permeability induced by dexamethasone in cultured rat brain endothelial cells.
The blood-brain barrier (BBB) plays an important role in controlling the passage of molecules from the blood to the extracellular fluid environment of the brain. An immortalised rat brain endothelial cell line (GPNT) was used to investigate the mechanisms underlying dexamethasone-induced decrease in paracellular permeability. Following treatment with 1 microM dexamethasone there was a decrease in transmonolayer paracellular permeability mainly to sucrose, fluorescein and dextrans of up to 20 KDa. According to pore theory, these differences in permeability were consistent with a decrease in the number of pores between brain endothelial cells. This effect was accompanied by a concentration of filamentous actin and cortactin to the cell periphery. Concomitantly, the continuity of the tight junctional protein ZO-1 at the cell borders was improved and was associated with an increase in both ZO-1 and occludin expression. By contrast, the expression and distribution of adherens junctional proteins such as beta-catenin and p100/p120 remained unchanged. These observations suggest that glucocorticoids induce a more differentiated BBB phenotype in cultured brain endothelial cells through modification of tight junction structure.
Romero
Ignacio A
IA
Division of Cell Biology, Institute of Ophthalmology, University College London, Bath Street, London EC1V 9EL, UK. i.romero@open.ac.uk
Radewicz
Katrina
K
Jubin
Emmanuelle
E
Michel
C Charles
CC
Greenwood
John
J
Couraud
Pierre-Olivier
PO
Adamson
Peter
P
D000199:Actins / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply*; D002199:Capillary Permeability / Q000187:drug effects; D002460:Cell Line; D051356:Cortactin; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005938:Glucocorticoids / Q000494:pharmacology*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
D000199:Actins; D051356:Cortactin; C495870:Cttn protein, rat; D003598:Cytoskeletal Proteins; D005938:Glucocorticoids; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D003907:Dexamethasone