Inhibition of transforming growth factor-beta production in brain pericytes contributes to cyclosporin A-induced dysfunction of the blood-brain barrier.
: 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.
Takata
Fuyuko
F
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan.
Dohgu
Shinya
S
Yamauchi
Atsushi
A
Sumi
Noriko
N
Nakagawa
Shinsuke
S
Naito
Mikihiko
M
Tsuruo
Takashi
T
Shuto
Hideki
H
Kataoka
Yasufumi
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D019793:Fluorescein / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D053773:Transforming Growth Factor beta1; D016572:Cyclosporine; D019793:Fluorescein