title: Tumor necrosis factor-α-stimulated brain pericytes possess a unique cytokine and chemokine release profile and enhance microglial activation.
abstract: 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)-α, possessing a unique cytokine and chemokine release profile. This was characterized by marked release of interleukin (IL)-6 and macrophage inflammatory protein-1α. Furthermore, TNF-α-stimulated pericytes induced expression of inducible nitric oxide synthase and IL-1β 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-α-sensitive cells and as effectors of TNF-α through the release of proinflammatory factors, and that, as such, they have a role in inducing brain inflammation, should be considered.
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan; Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan. Electronic address: jmatsumoto@fukuoka-u.ac.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Matsumoto
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan; BBB Laboratory, PharmaCo-Cell Co., Ltd., Nagasaki, Japan. Electronic address: ftakata@fukuoka-u.ac.jp.
authors.forename: Fuyuko
authors.initials: F
authors.lastname: Takata
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan. Electronic address: tmachida@fukuoka-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Machida
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan. Electronic address: hiro.takahashi0915@gmail.com.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan. Electronic address: pp090100@cis.fukuoka-u.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Soejima
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan. Electronic address: pp100038@cis.fukuoka-u.ac.jp.
authors.forename: Miho
authors.initials: M
authors.lastname: Funakoshi
authors.affiliation: Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan. Electronic address: futagami@fukuoka-u.ac.jp.
authors.forename: Koujiro
authors.initials: K
authors.lastname: Futagami
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan. Electronic address: atyama@fukuoka-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamauchi
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan. Electronic address: dohgu@fukuoka-u.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Dohgu
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan; BBB Laboratory, PharmaCo-Cell Co., Ltd., Nagasaki, Japan. Electronic address: ykataoka@fukuoka-u.ac.jp.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004660:Encephalitis / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism*; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018925:Chemokines; D016207:Cytokines; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase
keywords: Blood–brain barrier; Brain inflammation; Microglia; Neurovascular unit; Pericytes; Tumor necrosis factor-α