Masuda Takahiro, Iwamoto Shosuke, Mikuriya Satsuki, Tozaki-Saitoh Hidetoshi, Tamura Tomohiko, Tsuda Makoto, Inoue Kazuhide
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.
Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
J Pharmacol Sci. 2015 Aug;128(4):216-20. doi: 10.1016/j.jphs.2015.08.002. Epub 2015 Aug 15.
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.
干扰素调节因子8（IRF8）通过调节多种基因的表达，在小胶质细胞向反应性状态的转变中起关键作用。在本研究中，我们表明IRF1是小胶质细胞中IRF8诱导基因表达所必需的。外周神经损伤以IRF8依赖的方式诱导脊髓小胶质细胞中IRF1基因上调。在培养的小胶质细胞中转导IRF8可诱导IRF1的从头基因表达。重要的是，在转导IRF8的小胶质细胞中敲低IRF1基因可阻止白细胞介素-1β（IL-1β）的上调。因此，我们的研究结果表明，在表达IRF8的反应性小胶质细胞中，IL-1β的表达依赖于IRF1。
