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PMID: 17192829 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inhibition of transforming growth factor-beta production in brain pericytes contributes to cyclosporin A-induced dysfunction of the blood-brain barrier.

Cellular and molecular neurobiology ·Vol. 27 ·No. 3 ·2007-05-00 ·Pages 317-28

Takata F, Dohgu S, Yamauchi A, Sumi N, Nakagawa S, Naito M, Tsuruo T, Shuto H, Kataoka Y

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.

MeSH Terms
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism,physiology Animals Blood-Brain Barrier/drug effects,metabolism,physiology Brain/drug effects,metabolism Cell Membrane Permeability/drug effects Cells, Cultured Cyclosporine/pharmacology Down-Regulation/drug effects Endothelial Cells/drug effects,metabolism Fluorescein/pharmacokinetics Humans Mice Mice, Inbred BALB C Pericytes/drug effects,metabolism Transforming Growth Factor beta1/genetics,pharmacology,physiology
Chemicals
ATP Binding Cassette Transporter, Subfamily B, Member 1 Transforming Growth Factor beta1 Cyclosporine Fluorescein
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Takata Fuyuko
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan.
Dohgu Shinya
Yamauchi Atsushi
Sumi Noriko
Nakagawa Shinsuke
Naito Mikihiko
Tsuruo Takashi
Shuto Hideki
Kataoka Yasufumi
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Article Info
Journal
Cellular and molecular neurobiology
Abbr.
Cell Mol Neurobiol
ISSN
0272-4340
DOI
10.1007/s10571-006-9125-x
Published
2007-05-00
Epub
2006-00-28
Pages
317-28
Language
English
Region
United States
NLM ID
8200709
Subset
IM
External Links
PubMed source DOI: 10.1007/s10571-006-9125-x View journal details
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