Tumor necrosis factor-alpha mediates the blood-brain barrier dysfunction induced by activated microglia in mouse brain microvascular endothelial cells.
The present study was designed to elucidate the involvement of tumor necrosis factor-alpha (TNF-alpha) release from activated microglia in the induction of blood-brain barrier (BBB) dysfunction in an in vitro co-culture system with mouse brain capillary endothelial cells (MBEC4) and microglia. Lipopolysaccharide (LPS)-activated microglia increased the permeability of MBEC4 cells to sodium-fluorescein, and this hyper-permeability was blocked by a neutralizing antibody against TNF-alpha. LPS stimulated microglia to facilitate TNF-alpha release. These findings suggested that TNF-alpha released from activated microglia is attributable to BBB dysfunction.
Nishioku
Tsuyoshi
T
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan.
Matsumoto
Junichi
J
Dohgu
Shinya
S
Sumi
Noriko
N
Miyao
Kenji
K
Takata
Fuyuko
F
Shuto
Hideki
H
Yamauchi
Atsushi
A
Kataoka
Yasufumi
Y
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000503:physiopathology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D002463:Cell Membrane Permeability; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000378:metabolism; D019793:Fluorescein / Q000493:pharmacokinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019793:Fluorescein