TY - JOUR
T1 - Transcription factor IRF1 is responsible for IRF8-mediated IL-1β expression in reactive microglia
AU - Masuda, Takahiro
AU - Iwamoto, Shosuke
AU - Mikuriya, Satsuki
AU - Tozaki-Saitoh, Hidetoshi
AU - Tamura, Tomohiko
AU - Tsuda, Makoto
AU - Inoue, Kazuhide
N1 - Funding Information:
We thank Ms. Nao Nishimoto for assisting with the experiments and Dr. Keiko Ozato for kindly providing the Irf8 −/− mice. We also thank the Research Support Center (Graduate School of Medical Sciences, Kyushu University) for assisting with experiments and Dr. Hiroyuki Miyoshi (RIKEN BioResource Center) for providing the lentiviral vector and its packaging plasmids. This work was supported by grants from the Japan Society for the Promotion of Science (JSPS) through the “Funding Program for Next Generation World-Leading Researchers (NEXT Program)” initiated by the Council for Science and Technology Policy (CSTP) (M.T.) and the Ministry of Education, Culture, Sports, Science and Technology of Japan (T.M., M.T., K.I.), and from the Japan Science and Technology Agency (JST) through the Core Research for Evolutional Science and Technology (CREST) program (K.I.). The study was also supported by Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology, Japan .
Publisher Copyright:
© 2015 The Authors. Production and hosting by Elsevier B.V.
PY - 2015/9/4
Y1 - 2015/9/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jphs.2015.08.002
DO - 10.1016/j.jphs.2015.08.002
M3 - Article
C2 - 26318672
AN - SCOPUS:84940790549
SN - 1347-8613
VL - 128
SP - 216
EP - 220
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
IS - 4
ER -