FIGURE 2 Activation of the NALP3 inflammasome.
From the following article:
Primer: inflammasomes and interleukin 1
in inflammatory disorders
Leigh D Church, Graham P Cook and Michael F McDermott
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Figure 2. Activation of the NALP3 inflammasome.
Engagement of specific TLRs leads to activation of NF
B signaling pathways, inducing the expression of pro-IL-1
or pro-IL-18. NALP3 is the central component of the NALP3 inflammasome; in its inactive state the LRR domain of NALP3 is thought to self-associate, preventing interaction with CARDINAL or ASC. NALP3 activation by agonists, such as ATP, MDP, uric acid crystals, bacterial messenger RNA, or skin irritants, unfolds the NALP3 molecule, enabling the assembly of the inflammasome components CARDINAL, ASC, and procaspase 1 through homotypic interactions between their respective pyrin (PYD) and CARD domains; CARDINAL interacts with the NAD domain of NALP3 through its FIIND domain. The oligomerization of inflammasome complexes induces cleavage of procaspase 1 to its active form, resulting in the generation of active IL-1 from its inactive precursor pro-IL-1. VX-765 is a potent, selective, competitive inhibitor of caspase 1; COP, Iceberg, and PI9 can interfere with caspase activation. Several molecules (IL-1Ra, IRAP, and IL-1 mAbs) inhibit IL-1 activity. Abbreviations: ASC, apoptosis-associated speck-like protein containing a CARD; CARD, caspase-recruitment domain; COP, CARD-only protein; FIIND, domain with function to find; IL, interleukin; IL-1Ra, IL-1 receptor antagonist; IRAP, IL-1 receptor accessory protein; LRR, leucine-rich repeat; mAb, monoclonal antibody; MDP, muramyl dipeptide; MSU, monosodium urate; NACHT, domain present in neuronal apoptosis inhibitor protein (NAIP), major histocompatibility complex class II transactivator, HET-E (incompatibility locus protein from Podospora anserina) and telomerase-associated protein; NAD, NACHT-associated domain; NALP, NACHT domain, LRR domain, and pyrin domain-containing protein; NFB, nuclear factor B; PI9, proteinase inhibitor 9; PYD, pyrin domain; TLR, Toll-like receptor.