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

This article has now been updated. Please use the final version.

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 Advance online publication

Article ID: 09292SC

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

The final version of this article is now available: Vol. 112 (2010) , No. 2 p.251

Details

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 microvascular 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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