Fig. 8

Relationship between brain endothelial and glial cells in initiating the brain’s inflammatory response to IL-1β. In the setting of systemic inflammation, 1. circulating IL-1β binds to the IL-1R1 on the luminal surface of brain endothelial cells, 2. Endothelial cells release signals into the brain parenchyma that increase microglial IL-1β production, 3. Microglia-derived IL-1β engages IL-1R1 on the abluminal endothelial membrane, 4. Triggering the release of signals that increase microglial production of IL-1β, IL-6, and prostaglandins, 5. Astrocytes are also direct targets for microglia-derived IL-1β and activate microglia in a reciprocal fashion. Question marks indicate signaling molecules that have yet to be identified. This model explains how brain endothelial cells can differentially respond to inflammatory signals arising in the blood or brain and offers a mechanism by which brain endothelial and glial cells amplify, modify, and propagate inflammatory signaling within the CNS. IL-1RAcP IL-1R accessory protein, PG prostaglandins