Figure 2.

Schema of damage-associated molecular pattern (DAMP)- and pathogen-associated molecular pattern (PAMP)-mediated activation of innate immunity and inflammation. PAMPs and DAMPs released from infection and tissue injury, respectively, bind cell surface TLRs (Toll-like receptors) and PRRs (pattern-recognition receptors), leading to activation of NF-κB (nuclear factor-κB). NF-κB translocates to the nucleus and promotes expression of pro–IL-18, pro–IL1β, and NLRP3 (nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3). NLRP3 is deubiquinated and combines with apoptosis-associated speck-like protein (ASC) and pro–caspase-1 to form the NLRP3 inflammasome. The activated NLRP3 inflammasome converts pro–caspase-1 to caspase-1. Caspase-1 subsequently then catalyzes the production of mature IL-18 and IL-1β. Iκ-B = inhibitor of κ-B; RAGE = receptor for advanced glycation end-products.