Figure 1.

Transcriptional regulation of inflammation by GR in microglia. (A) In resting, healthy state without any cellular injury or pathogen invasion, GR is inactive in most microglia. Toxins e.g., MPTP or powerful inflammogen LPS would rapidly trigger innate immune response in microglia. In the case of LPS, TLR4 present in microglia results in activation of major transcription factors NF-κB, IRF and AP-1, known to orchestrate an inflammatory response. Cellular injury or pro-inflammatory cytokines would activate HPA axis and increased GC secretion. High circulating GC levels results in GR activation in microglia, which act to repress the transcriptional activity of NF-κB, IRF and AP-1 and also stimulating the expression of genes such as IκB-α and or MKP-1 known to inhibit NF-κB and AP-1 respectively. Neuronal injury and death are prevented. (B) In the absence of GR activity in microglia, microglia remain in activated state causing neuronal death.