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Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells.
Yonemoto, Kousuke; Fujii, Fumihiko; Taira, Ryoji; Ohgidani, Masahiro; Eguchi, Katsuhide; Okuzono, Sayaka; Ichimiya, Yuko; Sonoda, Yuri; Chong, Pin Fee; Goto, Hironori; Kanemasa, Hikaru; Motomura, Yoshitomo; Ishimura, Masataka; Koga, Yuhki; Tsujimura, Keita; Hashiguchi, Takao; Torisu, Hiroyuki; Kira, Ryutaro; Kato, Takahiro A; Sakai, Yasunari; Ohga, Shouichi.
Afiliação
  • Yonemoto K; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Fujii F; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Taira R; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Ohgidani M; Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Functional Anatomy and Neuroscience, Asahikawa Medical University, Hokkaido, Japan.
  • Eguchi K; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Okuzono S; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Section of Pediatrics, Department of Medicine, Fukuoka Dental College, Fukuoka, Japan.
  • Ichimiya Y; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Sonoda Y; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Chong PF; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Goto H; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Kanemasa H; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Motomura Y; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Ishimura M; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Koga Y; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Tsujimura K; Group of Brain Function and Development, Neuroscience Institute of the Graduate School of Science, Nagoya University, Aichi, Japan; Research Unit for Developmental Disorders, Institute for Advanced Research, Nagoya University, Aichi, Japan.
  • Hashiguchi T; Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
  • Torisu H; Section of Pediatrics, Department of Medicine, Fukuoka Dental College, Fukuoka, Japan.
  • Kira R; Department of Pediatric Neurology, Fukuoka Children's Hospital, Fukuoka, Japan.
  • Kato TA; Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Sakai Y; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: sakai.yasunari.530@m.kyushu-u.ac.jp.
  • Ohga S; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Clin Immunol ; 255: 109756, 2023 10.
Article em En | MEDLINE | ID: mdl-37678717
ABSTRACT
Microglia play versatile roles in progression of and protection against neuroinflammatory diseases. Little is known, however, about the mechanisms underlying the diverse reactivity of microglia to inflammatory conditions. We investigated how human induced microglia-like (iMG) cells respond to innate immune ligands. Quantitative PCR showed that poly-IC and lipopolysaccharide (LPS) activated the expression of IL1B and TNF. Immunoreactivity of iMG did not differ between controls (n = 11) and patients with neuroinflammatory diseases (n = 24). Flow cytometry revealed that CD14high cells expressed interleukin (IL) -1ß after LPS treatment. Immunoblotting showed that poly-IC and LPS differentially activated inflammatory pathways but commonly induced mitochondrial instability and the expression of pyruvate kinase isoform M2 (PKM2). Furthermore, a potent stimulator of PKM2 (DASA-58) alleviated IL-1ß production after LPS treatment. These data indicate that heterogeneous cell populations and mitochondrial stability underlie the divergent immunoreactivity of human iMG in environments.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Microglia / Doenças Neuroinflamatórias Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Microglia / Doenças Neuroinflamatórias Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article