IndraLab

Statements



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"Despite the inability of these inhibitors to trigger efflux of intracellular potassium, the addition of high extracellular potassium suppressed activation of the NLRP3 inflammasome."

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"In contrast, NLRP3 inflammasome activation could be blocked by high concentrations of extracellular potassium (30-45 mM)."

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"The ability of high extracellular potassium to suppress activation of the NLRP3 inflammasome by multiple proinflammatory agonists XREF_BIBR has been used to support a model demonstrating that decreased cellular potassium constitutes a general trigger for inflammasome activation."

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"Our data suggest that cells in high potassium may suppress the activation of the NLRP3 inflammasome by two independent mechanisms : 1) by restoring intracellular potassium to normal levels in cells that have undergone leakage of potassium via pore formation (e.g. by nigericin) or stimulation of P2X7 receptors (e.g. by ATP), thereby preventing translational inhibition; and 2) by suppressing the activation of caspase-1 by an unknown mechanism."

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"The decrease in intracellular K+ activates then NLRP3, producing IL-1β and IL-18 that are released from the cell throughout the gasdermin-N pores."

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"In ischemic stroke, the increase in cytosolic Ca2+ and the decrease in K+ is determined to activate NLRP3."

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"In this study, Petrilli et al. showed that reduced intracellualar K+ can effectively activate NLRP3 inflammasome (160)."

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"K + efflux is proposed as an important event upstream of NLRP3 inflammasome activation, and the decrease in intracellular K+ can activate the NLRP3 inflammasome; however, the mechanisms of potassium efflux during NLRP3 inflammasome activation is not understood."

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"As expected, increased extracellular potassium also inhibited Nlrp3 dependent silica induced, but not AIM2 dependent Francisella tularensis LVS induced, IL-1beta production (XREF_FIG)."

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"Because increased extracellular potassium blocks the activation of the NLRP3 inflammasome by MSU, it has been concluded that MSU acts through a mechanism that involves a decreased concentration of cellular potassium XREF_BIBR, XREF_BIBR, XREF_BIBR."

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"This leads to a potassium dysregulation and activation of NLRP3."

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"Many of these agents are capable of triggering K+ efflux from the cell, and indeed, addition of excess K+ to the extracellular space suppresses activation of the NLRP3 inflammasome and IL-1beta releas[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Firstly, recent studies suggest a central role for P2X7 receptor mediated K+ efflux in NLRP3 activation, with prevention of K+ efflux abolishing NLRP3 in response to almost all known activators."

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"Interestingly, higher levels of extracellular K+ significantly reduced the PrP106-126-induced NALP3 upregulation (64% of the mRNA level seen in microglia treated with PrP106-126 only) but had no effect on ASC upregulation."

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"It has also been described that potassium efflux is required for NLRP3 activation by various stimuli, a notion that was mainly attributed to the fact that potassium ionophores (e.g. Nigericin) are strong activators of the NLRP3 inflammasome, whereas high extracellular potassium concentrations that block K + efflux potently inhibit NLRP3 activation."

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"ATP induced loss of intracellular potassium induces the activation of the NALP3 inflammasome."

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"We also examined caspase-1 activation in infected wild-type and NLRC4 deficient macrophages in the presence of a high concentration of extracellular potassium (XREF_SUPPLEMENTARY), which is known to inhibit NLRP3 inflammasome activation XREF_BIBR."

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"For example, Gov et al. [XREF_BIBR] demonstrated that addition of extracellular potassium inhibited NLRP3 activation in response to Toxoplasma gondii infection."

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"The conclusion that decreased intracellular potassium acts as a second signal to trigger activation of the NLRP3 inflammasome was based initially on the observation that loss of potassium induced by nigericin, a potassium ionophore, or by ATP results in the robust release of IL-1beta from cells in an NLRP3 dependent manner XREF_BIBR, XREF_BIBR."

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"In addition, high extracellular concentrations of potassium prevent NLRP3 inflammasome activation, whereas low intracellular concentrations of potassium are sufficient to activate the NLRP3 inflammasome in macrophages."

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"Reductions in intracellular K+ levels can activate the NLRP3 inflammasome by influencing pore-forming or endogenous ion channels [41]."

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"Potassium efflux and reduced intracellular potassium concentrations result in activation of the NLRP3 inflammasome."

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"In potassium efflux model, extracellular ATP activates purine-type membrane receptor P2X7, results in potassium efflux, and consequently reduces intracellular potassium levels, thus activating NLRP3 inflammasome40)."

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"High extracellular potassium concentrations are known to inhibit NLRP3-mediated inflammasome activation (Petrilli et al., 2007)."

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"How NLRP3 inflammasome senses potassium efflux is still unknown, but one recently proposed model is that the loss of intracellular potassium promotes NLRP3 inflammasome activation by triggering a structural change of NLRP3 into its active conformation [36] ."

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"Reduction of intracellular potassium level induces a conformational change of NLRP3 allowing its activation [XREF_BIBR, XREF_BIBR]."

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"Notably, reduction of the intracellular K+ concentration was sufficient to activate NLRP3, whereas an increase in intracellular Na+ modulated but was not strictly required for inflammasome activation."

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"Potassium efflux is implicated in the activation mechanism for the inflammasome, because NLRP3 inflammasome activation can be triggered by low intracellular potassium, but prevented by culturing cells in high potassium containing media."

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"Our results demonstrating the rescue of protein translation by increased extracellular potassium in BMDM exposed to nigericin or ATP (XREF_FIG) suggested to us that impairment of ribosomal activity may explain why loss of cellular potassium activates the NLRP3 inflammasome."

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"It has been shown that reduction of the intracellular K+ concentration can activate the NLRP3 inflammasome, linking ion efflux to innate immunity [XREF_BIBR]."

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"One study has demonstrated that because of autocrine and paracrine P2X7 activation by secreted ATP, a decrease in K+ levels (<90 mM) in the cytoplasm can activate NLRP3 inflammasome."

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"Previous study has found that high extracellular potassium concentration (130mM) can block the activation of NALP3 inflammasome and inhibit the activation of caspase-1."

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"First, a large reduction of intracellular potassium concentration was observed to activate the NLRP3 inflammasome by ATP, nigericin, and crystal molecules."

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"Initial studies showed that the depletion of K+ in the cytosol with ATP, nigericin, or crystals was sufficient to activate NLRP3, while high levels of external K+ blocked this activation [98,99,100]."

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"Polydatin attenuates potassium oxonate induced hyperuricemia and kidney inflammation by inhibiting NF-kappaB and NLRP3 inflammasome activation via the AMPK and SIRT1 pathway."

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"To elucidate the role of potassium efflux as an upstream signal of NLRP3 inflammasome activation, equine PBMCs were treated with blockers of potassium efflux in the presence of NLRP3 triggers."