학술논문

Heterogeneity and mitochondrial vulnerability configurate the divergent immunoreactivity of human induced microglia-like cells.
Document Type
Academic Journal
Author
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.
Source
Publisher: Academic Press Country of Publication: United States NLM ID: 100883537 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-7035 (Electronic) Linking ISSN: 15216616 NLM ISO Abbreviation: Clin Immunol Subsets: MEDLINE
Subject
Language
English
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-I:C 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 CD14 high cells expressed interleukin (IL) -1β after LPS treatment. Immunoblotting showed that poly-I:C 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-1β production after LPS treatment. These data indicate that heterogeneous cell populations and mitochondrial stability underlie the divergent immunoreactivity of human iMG in environments.
Competing Interests: Declaration of Competing Interest None.
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