Abstract
: 1. The present study was designed to clarify whether brain pericytes and pericyte-derived transforming growth factor-beta1 (TGF-beta1) participate in cyclosporin A (CsA)-induced dysfunction of the blood-brain barrier (BBB).2. The presence of brain pericytes markedly aggravated CsA-increased permeability of MBEC4 cells to sodium fluorescein and accumulation of rhodamine 123 in MBEC4 cells.3. Exposure to CsA significantly decreased the levels of TGF-beta1 mRNA in brain pericytes in pericyte co-cultures. Treatment with TGF-beta1 dose-dependently inhibited CsA-induced hyperpermeability and P-glycoprotein dysfunction of MBEC4 cells in pericyte co-cultures.4. These findings suggest that an inhibition of brain pericyte-derived TGF-beta1 contributes to the occurrence of CsA-induced dysfunction of the BBB.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
-
Animals
-
Blood-Brain Barrier / drug effects*
-
Blood-Brain Barrier / metabolism*
-
Blood-Brain Barrier / physiology
-
Brain / drug effects*
-
Brain / metabolism
-
Cell Membrane Permeability / drug effects
-
Cells, Cultured
-
Cyclosporine / pharmacology*
-
Down-Regulation / drug effects
-
Endothelial Cells / drug effects
-
Endothelial Cells / metabolism
-
Fluorescein / pharmacokinetics
-
Humans
-
Mice
-
Mice, Inbred BALB C
-
Pericytes / drug effects*
-
Pericytes / metabolism
-
Transforming Growth Factor beta1 / genetics*
-
Transforming Growth Factor beta1 / pharmacology
-
Transforming Growth Factor beta1 / physiology
Substances
-
ATP Binding Cassette Transporter, Subfamily B, Member 1
-
Transforming Growth Factor beta1
-
Cyclosporine
-
Fluorescein