Tumor Necrosis Factor-α Mediates the Blood–Brain Barrier Dysfunction Induced by Activated Microglia in Mouse Brain Microvascular Endothelial Cells

Tsuyoshi Nishioku; Junichi Matsumoto; Shinya Dohgu; Noriko Sumi; Kenji Miyao; Fuyuko Takata; Hideki Shuto; Atsushi Yamauchi; Yasufumi Kataoka

doi:10.1254/jphs.09292SC

Short Communications

Tumor Necrosis Factor-α Mediates the Blood–Brain Barrier Dysfunction Induced by Activated Microglia in Mouse Brain Microvascular Endothelial Cells

Tsuyoshi Nishioku, Junichi Matsumoto, Shinya Dohgu, Noriko Sumi, Kenji Miyao, Fuyuko Takata, Hideki Shuto, Atsushi Yamauchi, Yasufumi Kataoka

Author information

Tsuyoshi Nishioku
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
Junichi Matsumoto
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
Shinya Dohgu
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
Noriko Sumi
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
Kenji Miyao
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
Fuyuko Takata
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
BBB Laboratory, PharmaCo-Cell Co., Ltd., Japan
Hideki Shuto
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
Atsushi Yamauchi
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
Yasufumi Kataoka
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
BBB Laboratory, PharmaCo-Cell Co., Ltd., Japan

Keywords: microglia, tumor necrosis factor-α (TNF-α), blood–brain barrier

JOURNAL FREE ACCESS

2010 Volume 112 Issue 2 Pages 251-254

DOI https://doi.org/10.1254/jphs.09292SC

View "Advance Publication" version (January 30, 2010).

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Abstract

The present study was designed to elucidate the involvement of tumor necrosis factor-α (TNF-α) 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-α. LPS stimulated microglia to facilitate TNF-α release. These findings suggested that TNF-α released from activated microglia is attributable to BBB dysfunction.

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