Figure 11.

Model for the role of MR and GR in regulating neuroinflammation in BV-2 cells. This study suggests that MR promotes a neuroinflammatory response mediated through NF-κB activation, which can be blocked by activation GR. The control of local glucocorticoid availability by 11β-HSD1 is important in regulating the fine-tuning of the balance between MR and GR activity. Corticosterone binds with high affinity to MR, followed by binding to GR with lower affinity. 11β-HSD1 inhibitors (such as T0504) block the differential effects of 11-dehydrocorticosterone on MR and GR. IL-6 stimulated 11β-HSD1 expression, suggesting that IL-6 is involved in a regulatory feed-forward mechanism to adjust the local levels of active glucocorticoids and therefore the balance between MR and GR. IL-6 and TNFR2 activation both lead to the activation of NF-κB, and their own expression is upregulated upon NF-κB activation.