Author:
Próchnicki Tomasz,Mangan Matthew S.,Latz Eicke
Abstract
Inflammasomes are high-molecular-weight protein complexes that are formed in the cytosolic compartment in response to danger- or pathogen-associated molecular patterns. These complexes enable activation of an inflammatory protease caspase-1, leading to a cell death process called pyroptosis and to proteolytic cleavage and release of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Along with caspase-1, inflammasome components include an adaptor protein, ASC, and a sensor protein, which triggers the inflammasome assembly in response to a danger signal. The inflammasome sensor proteins are pattern recognition receptors belonging either to the NOD-like receptor (NLR) or to the AIM2-like receptor family. While the molecular agonists that induce inflammasome formation by AIM2 and by several other NLRs have been identified, it is not well understood how the NLR family member NLRP3 is activated. Given that NLRP3 activation is relevant to a range of human pathological conditions, significant attempts are being made to elucidate the molecular mechanism of this process. In this review, we summarize the current knowledge on the molecular events that lead to activation of the NLRP3 inflammasome in response to a range of K+ efflux-inducing danger signals. We also comment on the reported involvement of cytosolic Ca2+ fluxes on NLRP3 activation. We outline the recent advances in research on the physiological and pharmacological mechanisms of regulation of NLRP3 responses, and we point to several open questions regarding the current model of NLRP3 activation.
Subject
General Pharmacology, Toxicology and Pharmaceutics,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference90 articles.
1. IL-1 beta maturation: evidence that mature cytokine formation can be induced specifically by nigericin.;D Perregaux;J Immunol.,1992
2. Interleukin-1 beta maturation and release in response to ATP and nigericin. Evidence that potassium depletion mediated by these agents is a necessary and common feature of their activity.;D Perregaux;J Biol Chem.,1994
3. Potassium-inhibited processing of IL-1 beta in human monocytes.;I Walev;EMBO J.,1995
4. Cryopyrin activates the inflammasome in response to toxins and ATP.;S Mariathasan;Nature.,2006
5. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter.;R Muñoz-Planillo;Immunity.,2013
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