p(HGNC:NLRP3)
A few molecules, such as amyloid-β, can induce both NLRP3 priming through TLR activation and NLRP3 inflammasome activation68. PubMed:23702978
This channel senses intracellular ROS and responds by opening itself to facilitate Ca2+ influx into the cell; this is intriguing considering that both ion fluxes and the oxidative state (see below) have important roles in NLRP3 inflammasome activation. PubMed:23702978
Finally, heat shock proteins (HSPs) also have important roles in the regulation of cell death, and it has been shown that HSP90 and the cochaperone ubiquitin ligase-associated protein SGT1 are required for NLRP3 activation (REF. 129). PubMed:23702978
Furthermore, the amount of NLRP3 mRNA is tightly regulated by the microRNA miR-223, which leads to decreased NLRP3 protein levels and, thus, influences the threshold of NLRP3 activation74,75. PubMed:23702978
First, a bacterial Toll-like receptor (TLR) activator leads to cellular priming and upregulation of NLRP3 and pro-IL-1β expression (the priming checkpoint in the standard model)37,38. PubMed:23702978
Many innate immune signalling or cytokine receptors, such as the TNFR, activate transcription of NLRP3 and thereby influence the susceptibility of immune cells to NLRP3 inflammasome triggers37,38 (FIG. 2). PubMed:23702978
In addition, T cell-derived IFNγ has been shown to downregulate the activity of NLRP3 via activation of inducible nitric oxide synthase (iNOS) in a mouse model of tuberculosis71; nitric oxide (NO) induces NLRP3 nitrosylation and thereby inhibits NLRP3 activity. PubMed:23702978
In addition, T cell-derived IFNγ has been shown to downregulate the activity of NLRP3 via activation of inducible nitric oxide synthase (iNOS) in a mouse model of tuberculosis71; nitric oxide (NO) induces NLRP3 nitrosylation and thereby inhibits NLRP3 activity. PubMed:23702978
Another transient receptor potential channel — TRPM2 — has also been implicated in NLRP3 activation in response to crystalline substances88. PubMed:23702978
In AD, microglial cells and astrocytes express NLRP3, which in turn can detect A beta plaques and act by secreting caspase-1 to activate IL-1 beta and IL- 18 [23–25]. PubMed:27314526
In AD, microglial cells and astrocytes express NLRP3, which in turn can detect A beta plaques and act by secreting caspase-1 to activate IL-1 beta and IL- 18 [23–25]. PubMed:27314526
In AD, microglial cells and astrocytes express NLRP3, which in turn can detect A beta plaques and act by secreting caspase-1 to activate IL-1 beta and IL- 18 [23–25]. PubMed:27314526
Most studies concerning the pathophysiological roles of heme have focused on the protective effect of the heme-degrading enzyme, heme oxygenase 1 (HO-1) [25] (Box 2), and on the effect of this danger-associated molecule on cells, leading to oxidative stress, TLR4 signaling [26,27], and NLRP3 inflammasome activation [28] (Box 4). PubMed:26875449
It has been reported that an increase in extracellular heme activates NLRP3 expression, triggering inflammasome activation [28]. PubMed:30248094
As a component of inflammasome, NLRP3 is the best characterized member of NLRs, which recruits and activates caspase-1 via the adapter molecule ASC (apoptosis- associated speck-like protein containing caspase activation and recruitment domain) [8, 9]. PubMed:24464629
. Interestingly, NLRP3 knockdown and mROS inhibitors reduce brain edema and improve neurological functions (Ma et al., 2014). PubMed:24904418
In AD, microglial cells and astrocytes express NLRP3, which in turn can detect A beta plaques and act by secreting caspase-1 to activate IL-1 beta and IL- 18 [23–25]. PubMed:27314526
In AD, microglial cells and astrocytes express NLRP3, which in turn can detect A beta plaques and act by secreting caspase-1 to activate IL-1 beta and IL- 18 [23–25]. PubMed:27314526
As a component of inflammasome, NLRP3 is the best characterized member of NLRs, which recruits and activates caspase-1 via the adapter molecule ASC (apoptosis- associated speck-like protein containing caspase activation and recruitment domain) [8, 9]. PubMed:24464629
. Interestingly, NLRP3 knockdown and mROS inhibitors reduce brain edema and improve neurological functions (Ma et al., 2014). PubMed:24904418
Indeed, TLRs and NLRP3 have been associated with atherosclerosis development. PubMed:24904418
It has been reported that an increase in extracellular heme activates NLRP3 expression, triggering inflammasome activation [28]. PubMed:30248094
It has been reported that an increase in extracellular heme activates NLRP3 expression, triggering inflammasome activation [28]. PubMed:30248094
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.