Oncostatin-M-Reactive Pericytes Aggravate Blood–Brain Barrier Dysfunction by Activating JAK/STAT3 Signaling In Vitro

Fuyuko Takata, Shinya Dohgu, Shinya Sakaguchi, Kenta Sakai, Gaku Yamanaka, Takuro Iwao, Junichi Matsumoto, Ikuya Kimura, Yume Sezaki, Yoshie Tanaka, Atsushi Yamauchi, Yasufumi Kataoka

研究成果: ジャーナルへの寄稿学術誌査読

7 被引用数 (Scopus)

抄録

Oncostatin M (OSM) is a cytokine of the interleukin (IL)-6 family members. It induces blood–brain barrier (BBB) dysfunction by activating Janus-activated kinase (JAK) and signal transducer and activator of transcription (STAT) 3 pathways in brain endothelial cells. Brain pericytes located around microvessels are one of the BBB constituents. Pericytes work as a boundary surface between the blood circulation and brain parenchyma, and their functions are altered under pathophysiological conditions, leading to BBB dysregulation. However, it remains unknown whether pericytes are associated with OSM-induced BBB dysfunction. We demonstrated that pericyte exposure to OSM (100 ng/mL) elevated phosphorylation of STAT3, a main OSM signaling pathway, and that pericytes expressed OSM receptors (OSMRs) including OSMRβ and glycoprotein 130. These results suggest that pericytes are able to respond to OSM. To determine the effects of OSM-reactive pericytes on BBB functions, rat brain endothelial cell (RBEC) monolayers were cultured with OSM-treated pericytes. The presence of pericytes exposed to 100 ng/mL of OSM for 48 h aggravated both the elevated permeability to sodium fluorescein and the lowered transendothelial electrical resistance which were induced by OSM in RBECs. This OSM-reactive pericyte-induced aggravation of lowered RBEC barrier function was reversed by ruxolitinib, a JAK inhibitor. These findings suggest that activated JAK/STAT3 signaling in pericytes contributes to OSM-produced BBB breakdown. Thus, OSM-reactive pericytes may have to be considered a characteristic machinery in the formation and progression of BBB breakdown under pathological conditions associated with increased OSM levels.

本文言語英語
ページ(範囲)12-20
ページ数9
ジャーナルNeuroscience
422
DOI
出版ステータス出版済み - 12月 1 2019
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 神経科学(全般)

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