Toll-like Receptor 2 Induces Interferon Regulatory Factor 8 (IRF8) Expression in Spinal Cord Microglia

Abstract

It has been reported that spinal cord microglia activation is critical for neuropathic pain by peripheral nerve injury (PNI). However, the mechanisms of microglia activation have not been completely elucidated. A recent study showed that interferon regulatory factor 8 (IRF8) is a key transcription factor responsible for the microglia activation due to PNI. Also, previous studies showed that Toll-like receptor 2 (TLR2) is involved in the PNI-induced spinal cord microglia activation. In this study, I investigated the role of TLR2 in IRF8 expression in spinal cord microglia after PNI. Lipoteichoic acid (LTA), a TLR2 agonist, stimulation induced IRF8 expression in primary glial cells. This induction needed p38 MAPK and NFB activation. In addition, depletion of NADPH oxidase 2 (Nox2)-derived ROS blocked IRF8 expression. Lastly, an intrathecal injection of LTA induced IRF8 mRNA expression in spinal cord. Conclusively, these data show that TLR2 induces IRF8 expression in spinal cord microglia, which may serve as a mechanism for the PNI-induced IRF8 expression in the spinal cord microglia.