Abstract
Chronic inflammatory responses have long been observed to be associated with various types of cancer and play decisive roles at different stages of cancer development. Inflammasomes, which are potent inducers of interleukin (IL)-1β and IL-18 during inflammation, are large protein complexes typically consisting of a Nod-like receptor (NLR), the adapter protein ASC, and Caspase-1. During malignant transformation or cancer therapy, the inflammasomes are postulated to become activated in response to danger signals arising from the tumors or from therapy-induced damage to the tumor or healthy tissue. The activation of inflammasomes plays diverse and sometimes contrasting roles in cancer promotion and therapy depending on the specific context. Here we summarize the role of different inflammasome complexes in cancer progression and therapy. Inflammasome components and pathways may provide novel targets to treat certain types of cancer; however, using such agents should be cautiously evaluated due to the complex roles that inflammasomes and pro-inflammatory cytokines play in immunity.
Highlights
Inflammasomes are multimolecular complexes that promote inflammation and inflammatory cell death through the activation of cysteine protease caspase-1 in response to both microbial insults to the host and endogenous damage-associated molecular patterns (DAMPS) such as uric acid and extracellular ATP
Inflammasomes, which are potent inducers of interleukin (IL)-1β and IL-18 during inflammation, are large protein complexes typically consisting of a Nod-like receptor (NLR), the adapter protein a caspase recruitment domain (ASC), and Caspase-1
Inflammasome complexes are typically comprised of an NLR which interacts directly with caspase-1 through a caspase activation and recruitment domain (CARD) or via an adapter protein, usually apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC; known as Pycard), which links the NLR to caspase-1
Summary
Inflammasomes are multimolecular complexes that promote inflammation and inflammatory cell death (referred to as pyroptosis) through the activation of cysteine protease caspase-1 in response to both microbial insults to the host and endogenous damage-associated molecular patterns (DAMPS) such as uric acid and extracellular ATP. The first step involves the induction of mRNA and protein expression of pro-IL-1β and pro-IL-18, a procedure mediated by NF-κB activation. Priming readies inflammasomes for activation; one possible mechanism for this is postulated to be the upregulation of NLRP3 expression in response to LPS. A study by Shcroder et al showed that LPS can augment inflammasome activation independently from NLRP3 expression, suggesting that other mechanism for priming exists (Bauernfeind et al, 2009; Schroder et al, 2012). A recent study by Juliana et al showed that mitochondria-derived reactive oxygen species (ROS) can prime the NLRP3 inflammasome
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