Fig. 2. Two signals are required for NLRP3 inflammasome activation .

Signaling pathway. Signal 1: Toll-like receptors (TLRs) bind their cognate ligands such as lipopolysaccharides (LPS), trigger NF-κB signaling pathway, and ultimately lead to the expression of pro-IL-18, pro-IL-1β, and NLRP3 protein. Signal 2: DAMP (damage-associated molecular patterns) and PAMPs (pathogen-associated molecular patterns) are recognized by NLRP3, causing NLRP3-ASC-pro-caspase-1 inflammasome assembly and activation, which convert inactive caspase 1 to active caspase 1 and subsequently cleaves pro-IL-18 or pro-IL-1β to corresponding active form.