title: Transcription factor IRF1 is responsible for IRF8-mediated IL-1β expression in reactive microglia.
abstract: Interferon regulatory factor-8 (IRF8) plays a crucial role in the transformation of microglia to a reactive state by regulating the expression of various genes. In the present study, we show that IRF1 is required for IRF8-induced gene expression in microglia. Peripheral nerve injury induced IRF1 gene upregulation in the spinal microglia in an IRF8-dependent manner. IRF8 transduction in cultured microglia induced de novo gene expression of IRF1. Importantly, knockdown of the IRF1 gene in IRF8-transduced microglia prevented upregulation of interleukin-1β (IL-1β). Therefore, our findings suggest that expression of IL-1β is dependent on IRF1 in IRF8-expressing reactive microglia.
authors: Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Institute of Neuropathology, University of Freiburg, Neurozentrum, Breisacherstraße 64, Freiburg 79106, Germany; Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Tokyo 102-0076, Japan.
authors: Takahiro
authors: T
authors: Masuda
authors: Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Shosuke
authors: S
authors: Iwamoto
authors: Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Satsuki
authors: S
authors: Mikuriya
authors: Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Tokyo 102-0076, Japan.
authors: Hidetoshi
authors: H
authors: Tozaki-Saitoh
authors: Department of Immunology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kansazawa-ku, Yokohama 236-0004, Japan.
authors: Tomohiko
authors: T
authors: Tamura
authors: Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: tsuda@phar.kyushu-u.ac.jp.
authors: Makoto
authors: M
authors: Tsuda
authors: Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Tokyo 102-0076, Japan. Electronic address: inoue@phar.kyushu-u.ac.jp.
authors: Kazuhide
authors: K
authors: Inoue
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D050856:Interferon Regulatory Factor-1 / Q000502:physiology*; D050835:Interferon Regulatory Factors / Q000502:physiology*; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology* / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology; D015854:Up-Regulation / Q000235:genetics; D000099185:Interferon Regulatory Factor-8
chemical_list: D050856:Interferon Regulatory Factor-1; D050835:Interferon Regulatory Factors; D053583:Interleukin-1beta; D000099185:Interferon Regulatory Factor-8; C494258:Irf1 protein, mouse
keywords: IL-1β; Interferon regulatory factor; Microglia