Brain pericytes contribute to the induction and up-regulation of blood-brain barrier functions through transforming growth factor-beta production.
The blood-brain barrier (BBB) is a highly organized multicellular complex consisting of an endothelium, brain pericytes and astrocytes. The present study was aimed at evaluating the role of brain pericytes in the induction and maintenance of BBB functions and involvement of transforming growth factor-beta (TGF-beta) in the functional properties of pericytes. We used an in vitro BBB model established by coculturing immortalized mouse brain capillary endothelial (MBEC4) cells with a primary culture of rat brain pericytes. The coculture with rat pericytes significantly decreased the permeability to sodium fluorescein and the accumulation of rhodamine 123 in MBEC4 cells, suggesting that brain pericytes induce and up-regulate the BBB functions. Rat brain pericytes expressed TGF-beta1 mRNA. The pericyte-induced enhancement of BBB functions was significantly inhibited when cells were treated with anti-TGF-beta1 antibody (10 microg/ml) or a TGF-beta type I receptor antagonist (SB431542) (10 microM) for 12 h. In MBEC4 monolayers, a 12 h exposure to TGF-beta1 (1 ng/ml) significantly facilitated the BBB functions, this facilitation being blocked by SB431542. These findings suggest that brain pericytes contribute to the up-regulation of BBB functions through continuous TGF-beta production.
Dohgu
Shinya
S
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Takata
Fuyuko
F
Yamauchi
Atsushi
A
Nakagawa
Shinsuke
S
Egawa
Takashi
T
Naito
Mikihiko
M
Tsuruo
Takashi
T
Sawada
Yasufumi
Y
Niwa
Masami
M
Kataoka
Yasufumi
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D030201:Activin Receptors, Type I / Q000037:antagonists & inhibitors; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000166:cytology* / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D004149:Dioxoles / Q000494:pharmacology; D019793:Fluorescein / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000096:biosynthesis*; D020286:Pericytes / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D020112:Rhodamine 123 / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001549:Benzamides; D004149:Dioxoles; D005456:Fluorescent Dyes; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D020112:Rhodamine 123; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat; D019793:Fluorescein