Reduction of IRF8 by siRNA failed to enhance viability of OPCs after treatment with IFNg, although it partially but significantly decreased the number of preapoptotic cells. However, we still could not rule out a contribution of the endogenous IRF8 in the IFNg induced OPC apop tosis, because the transfection of the IRF8 siRNA Veliparib msds resulted in only a partial suppression Inhibitors,Modulators,Libraries against Inhibitors,Modulators,Libraries the robust IRF8 induction by IFNg. Together, these results support the notion that endogenous IRF8 positively regulates the IFNg induced OPC apoptosis depending on its induced dosage. We previously demonstrated that, unlike OPCs, mature myelin producing oligodendrocytes were totally resistant to IFNg induced apoptosis. Nevertheless, IRF1 was similarly induced by IFNg in mature oligo dendrocytes compared with OPCs.

We also confirmed that IFNg induced IRF8 mRNA at similar levels in both OPCs and mature oligodendrocytes. These results indicate that IRF1 mediated transcriptional activations may be necessary to activate the apoptotic cascade in OPCs, but are not sufficient. We speculate that differences in cellular context between OPCs and mature oligodendrocytes Inhibitors,Modulators,Libraries such as activities of ERK signaling are the other neces sary components for IFNg Inhibitors,Modulators,Libraries induced OPC apoptosis as well. Conclusions Conclusions from this study are summarized as follows. First, unlike IFNg, IFNb is far less capable of inducing OPC apoptosis. Second, our comprehensive analysis of the IRF family members in IFNg and IFNb treated OPCs identified that IRF1 and IRF8 are preferentially up regulated by IFNg.

Third, functional analyses Inhibitors,Modulators,Libraries of IRF1 and IRF8 revealed that not only IRF1 but also IRF8 con tribute to the IFNg mediated OPC apoptosis. This find ing will help us to identify downstream genes involved in OPC apoptosis. These transcription factors and their downstream target genes could be potential Ruxolitinib JAK therapeutic targets to enhance remyelination in MS. Background Inflammation plays a critical role in neurodegenerative diseases such as Parkinsons disease, multiple sclerosis, Alzheimers disease, and HIV associated dementia. Activation of microglia, the intrinsic macro phages in the central nervous system, is a characteristic feature of most neurodegenerative diseases upon systemic infection. Mounting evidence indicates that macrophage microglia activation contributes to inflammation and neuronal injury in a number of neu rological disorders. However, the cellular and molecular relationships between infections outside the CNS and potential neuronal loss within the CNS is elu sive. It is known that in response to certain environment toxins, macrophages microglia can enter into an overac tivated state and release inflammatory cytokines and reactive oxygen species that cause neurotoxicity.