Tumor necrosis factor-α-stimulated brain pericytes possess a unique cytokine and chemokine release profile and enhance microglial activation

被引:69
作者
Matsumoto, Junichi [1 ,3 ]
Takata, Fuyuko [1 ,2 ]
Machida, Takashi [1 ]
Takahashi, Hiroyuki [1 ]
Soejima, Yuki [1 ]
Funakoshi, Miho [1 ]
Futagami, Koujiro [3 ]
Yamauchi, Atsushi [1 ]
Dohgu, Shinya [1 ]
Kataoka, Yasufumi [1 ,2 ]
机构
[1] Fukuoka Univ, Fac Pharmaceut Sci, Dept Pharmaceut Care & Hlth Sci, Fukuoka 8140180, Japan
[2] PharmaCo Cell Co Ltd, BBB Lab, Nagasaki, Japan
[3] Fukuoka Univ, Fac Pharmaceut Sci, Dept Pharmaceut & Hlth Care Management, Fukuoka 8140180, Japan
基金
日本学术振兴会;
关键词
Pericytes; Tumor necrosis factor-alpha; Microglia; Neurovascular unit; Brain inflammation; Blood-brain barrier; TNF-ALPHA; MICROVASCULAR PERICYTES; NITRIC-OXIDE; IN-VITRO; CELL; BARRIER; MICE; EXPRESSION; MATRIX-METALLOPROTEINASE-9; LIPOPOLYSACCHARIDE;
D O I
10.1016/j.neulet.2014.06.052
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Brain pericytes are involved in neurovascular dysfunction, neurodegeneration and/or neuroinflammation. In the present study, we focused on the proinflammatory properties of brain pericytes to understand their participation in the induction of inflammation at the neurovascular unit (NVU). The NVU comprises different cell types, namely, brain microvascular endothelial cells, pericytes, astrocytes and microglia. Among these, we found pericytes to be the most sensitive to tumor necrosis factor (TNF)-alpha, possessing a unique cytokine and chemokine release profile. This was characterized by marked release of interleukin (IL)-6 and macrophage inflammatory protein-1 alpha. Furthermore, TNF-alpha-stimulated pericytes induced expression of inducible nitric oxide synthase and IL-1 beta mRNAs, as an index of BV-2 microglial cell activation state, to the highest levels. Based on these findings, the possibility that brain pericytes act specifically as TNF-alpha-sensitive cells and as effectors of TNF-alpha through the release of proinflammatory factors, and that, as such, they have a role in inducing brain inflammation, should be considered. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:133 / 138
页数:6
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