Transcription factor IRF1 is responsible for IRF8-mediated IL-1β expression in reactive microglia

Takahiro Masuda; Shosuke Iwamoto; Satsuki Mikuriya; Hidetoshi Tozaki-Saitoh; Tomohiko Tamura; Makoto Tsuda; Kazuhide Inoue

doi:10.1016/j.jphs.2015.08.002

Transcription factor IRF1 is responsible for IRF8-mediated IL-1β expression in reactive microglia

J Pharmacol Sci. 2015 Aug;128(4):216-20. doi: 10.1016/j.jphs.2015.08.002. Epub 2015 Aug 15.

Authors

Takahiro Masuda¹, Shosuke Iwamoto², Satsuki Mikuriya², Hidetoshi Tozaki-Saitoh³, Tomohiko Tamura⁴, Makoto Tsuda⁵, Kazuhide Inoue⁶

Affiliations

¹ 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.
² Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
³ 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.
⁴ Department of Immunology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kansazawa-ku, Yokohama 236-0004, Japan.
⁵ 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: [email protected].
⁶ 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: [email protected].

PMID: 26318672
DOI: 10.1016/j.jphs.2015.08.002

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.

Keywords: IL-1β; Interferon regulatory factor; Microglia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / genetics*
Cells, Cultured
Female
Gene Expression / genetics*
Gene Expression Regulation, Developmental / genetics*
Interferon Regulatory Factor-1 / physiology*
Interferon Regulatory Factors / physiology*
Interleukin-1beta / genetics*
Interleukin-1beta / metabolism
Male
Mice, Inbred C57BL
Mice, Knockout
Microglia / cytology*
Microglia / metabolism
Peripheral Nerve Injuries / genetics
Signal Transduction / genetics
Signal Transduction / physiology
Spinal Cord / cytology
Up-Regulation / genetics

Substances

Interferon Regulatory Factor-1
Interferon Regulatory Factors
Interleukin-1beta
Irf1 protein, mouse
interferon regulatory factor-8