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

• Published in: Journal of pharmacological sciences 2015-08, Vol.128 (4), p.216-220
• Main Authors: Masuda, Takahiro, Iwamoto, Shosuke, Mikuriya, Satsuki, Tozaki-Saitoh, Hidetoshi, Tamura, Tomohiko, Tsuda, Makoto, Inoue, Kazuhide
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - genetics; Cells, Cultured; Female; Gene Expression - genetics; Gene Expression Regulation, Developmental - genetics; IL-1β; Interferon regulatory factor; Interferon Regulatory Factor-1 - physiology; Interferon Regulatory Factors - physiology; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Male; Mice, Inbred C57BL; Mice, Knockout; Microglia; Microglia - cytology; Microglia - metabolism; Peripheral Nerve Injuries - genetics; Signal Transduction - genetics; Signal Transduction - physiology; Spinal Cord - cytology; Up-Regulation - genetics
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2015.08.002

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.