Two signals are required for NLRP3 inflammasome activation. Signal 1, also known as the priming signal, is mediated by microbial ligands recognised by TLRs or cytokines such as TNF-α which activate the NF-κB pathway, leading to upregulation of pro-IL-1β and NLRP3 protein levels (Bauernfeind et al. 2009, Jo et al. 2016). In the absence of TLR agonist 'priming', inflammasome dependent caspase-1 activation is observed but IL-1 beta secretion is minimal. This is primarily because pro-IL1 beta is not expressed in most cells until stimulated by proinflammatory signals such as TNF or LPS that activate NFkappaB. NFkappaB induces expression of pro-IL1beta that can be activated by caspase-1.
Horvath, G, Fitzgerald, KA, Stutz, A, Wu, J, Bauernfeind, FG, Latz, E, Hornung, V, Speert, D, Monks, BG, MacDonald, K, Alnemri, ES, Fernandes-Alnemri, T
Jo, EK, Shin, DM, Sasakawa, C, Kim, JK
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