upon IL1β and TNFα stimulation, which are essential enzymes for NO and reactive oxygen species (ROS) production, respectively. Knockdown of Nurr1 in astrocytes drastically increased mRNA expression of both iNOS and Ncf1 in response to IL1β and TNFα and up-regulated NO production (Fig. 5E–G and S11E-F). Furthermore, activated astrocytes can produce macrophage colony stimulating factor (CSF1), which supports the proliferation of microglia (Thery et al., 1992), and knockdown of Nurr1 significantly up-regulated the transcription of CSF1 gene upon both TNFα and IL1β stimulation (Fig. 5H and S11G). In contrast, transcription of brain-derived neurotrophic factor (BDNF), a known neurotrophin for dopaminergic neurons, was not affected by knockdown of Nurr1 (Fig. 5I and S11H). These data indicate that Nurr1 also acts as a transcriptional repressor for inflammatory neurotoxic mediators in astrocytes.
