Unified Modeling of Familial Mediterranean Fever and Cryopyrin Associated Periodic Syndromes

Figure 4

Maturation and secretion of IL-1β requires two signals. Binding of ligand (PAMP or IL-1β) to TLR (1) activates NF-κB pathway (2). NF-κB signaling results in proIL-1β transcription and secretion (3 and 4). Binding of ATP to the P2X7 receptor is considered as the activation signal (5) which causes K⁺ efflux (6) and subsequently a decrease in intracellular K⁺ concentration (7). Together with PAMP or DAMP, fall in K⁺ acts as the initiator of the inflammasome formation (7). ProIL-1β is cleaved by the product of the inflammasome, Caspase 1 (8a). However, Caspase 1 is not the only protease that can cleave proIL-1β (8b). Mature IL-1β is secreted and inflammation process is then started (9). Dashed path shows the positive feedback relationship between the free IL-1β (I) and bound IL-1β (R).