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"Importantly, the additional presence of glycine to attenuate cell lysis did not modulate the effects of the lanthanides on nigericin stimulated NLRP3 inflammasome signaling and IL-1beta export (XREF_FIG)."

"Decreases in extracellular Na + (from 140 mM to 15–40 mM) inhibited K + -free medium-, gramicidin-, or nigericin-induced NLRP3 activation, whereas it had no inhibitory effect on NLRP3 activation induc[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"To determine whether EOAA could inhibit the activation of the NLRP3 inflammasome induced by other stimulators, we activated the NLRP3 inflammasome with nigericin."

"MCC950 and Nigericin sodium salt (Nig) were used to inhibit or promote the activation of NLRP3 inflammasome pharmacologically, respectively."

"In order to identify the potential mechanisms, we further revealed that nigericin administration reversed the neuroprotective effect of melatonin by promoting NLRP3 inflammasome activation."

"NU6300 exhibited a quite strong inhibition effect on earlier steps of NLRP3 inflammasome, with a remarkable inhibition on ASC oligomerization, caspase-1 activation, GSDMD cleavage, membrane translocation, and the release of IL-1β in nigericin-triggered NLRP3 inflammasome (Fig. 6, A to F)."

"A total of 3287 small molecules were screened for inhibitors of nigericin-induced NLRP3 oligomerization."

"To demonstrate the effect of ADAM10 depletion was specific to Hla induced cell death and not generally suppressive of NLRP3 activation, siRNA transfected cells were also treated with nigericin, a pore forming toxin known to activate NLRP3, and assessed for cell death [XREF_BIBR]."

"Reduced NAD+ levels, in turn, inactivates the -tubulin deacetylase sirtuin 2 and promotes acetylated- microtubule, dynein dependent transport of perinuclear mitochondria to the ER-MAMs to bring ASC into the proximity of NLRP3 and drive inflammasome assembly.256 However, incompatible with this model is the fact that (i) prior to NLRP3 activation ASC is predominantly found in the nucleus and rapidly redistributes to the cytosol upon activation,257 (ii) other reports suggest that NLRP3 is localized to the mitochondria,160 and (iii) the lack of requirement for either mtROS and K+ efflux.256 MAVS was also proposed by the laboratory of Ronald Germain to tether NLRP3 to the mitochondria and facilitate activation to soluble (e.g., ATP and nigericin), but not particulate and crystallinematter (e.g., alum, cholesterol crystals, or MSU crystals).258 Challenging this study, several groups have now identified that while MAVS, and interacting protein mitofusin 2, are required for NLRP3 activation to RNA viruses, they do not impact canonical NLRP3 activation.122,246,259,260 Inner mitochondrial membrane phospholipid, cardiolipin, also allegedly binds NLRP3 to localize it to the mitochondria for activation, as knockdown of cardiolipin synthase attenuated NLRP3 activation.261 Nevertheless, it was recently suggested that mtROS generation at the inflammasome priming stage facilitates both NLRP3 and caspase-1 association with cardiolipin on the outer mitochondria membrane, and thus cardiolipin may act as scaffolding for NLRP3 inflammasome assembly, rather than its activation.262 Notably, if the mitochondria acts as the inflammatory platform and trigger, it remains to be reconciled why in many studies the active inflammasome appears to be cytosolic, as evidenced by a lack of co-localization of ASC specks with organelle markers.263 It is also noteworthy that the mitochondrial GTPase DRP1 has been suggested to be required for NLRP3 activation downstream of RIPK1-RIPK3 upon exposure to dsRNA or RNA viruses, although a latter study failed to reproduce these findings.264,265 It has also recently been proposed that the mitochondrial phosphatase PGAM5, which also maintains mitochondrial homeostasis and triggers mitophagy, is required for mtROS induced NLRP3 activation in macrophages to not only vesicular stomatosis virus infection but also soluble and particulate triggers.127 It therefore remains plausible that mitochondrial dysfunction may trigger NLRP3 activity under certain circumstances.4.3 THE MINOR PLAYERS4.3.1 Calcium mobilizationIntracellular Ca2+ was first implicated in ATP- and Nigericin induced NLRP3 activation in a study utilizing the Ca2+ chelator BAPTA-AM and ER-Ca2+ ATPase thapsigargin.266 Several studies have now reported that NLRP3 can be triggered by Ca2+ mobilization from the ER stores upon activation of G protein coupled calcium sensing receptor (CaSR) signaling, and Ca2+ influx induced via store operated-Ca2+ entry (SOCE) channels or cationic transient receptor potential (TRP) channels.214,241,244,267,268 Ca2+ mobilization from the ER stores was initially postulated to be a common event to trigger NLRP3 via CaSR, phospholipase C (PLC) and 1,4,5-triphosphate signaling."

"However, ASC oligomerization is necessary for all agonist induced NLRP3 inflammasome activation, so we speculate that Icariside I does not directly target ASC to exacerbate ATP or nigericin induced NLRP3 inflammasome activation."

"Consistent with these results, cleavage of caspase-1 and proIL-1β in nigericin-stimulated Nlrp3 CreT BMDMs was not inhibited by 1 μM CRID3 (Fig 6D), and pretreatment with 10 μM CRID3 was required to effectively abrogate the aforementioned inflammasome responses (Figs 6E and F and S5G)."

"In LPS-pretreated mouse BMDMs, whether ginseng saponins including protopanaxadiol saponins, protopanaxatriol saponins and oleanane saponins could inhibit nigericin-induced NLRP3 inflammasome was initi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"We observed that loading LPS primed BMDC with BAPTA markedly attenuated multiple readouts of nigericin stimulated NLRP3 inflammasome signaling including total IL-1beta release (XREF_FIG), extracellular accumulation of p20 caspase-1 subunit and p17 mature IL-1beta (XREF_FIG), formation of ASC oligomers (XREF_FIG), and induction of pyroptotic propidium 2+ influx (XREF_FIG)."

"Extracellular Rb -based buffer, but not a Li -based buffer, also blocked the stable NLRP3 BRET signal decrease induced by nigericin (Fig. 2C)."

"In no experiments did C4BP affect nigericin-induced responses, suggesting that C4BP specifically inhibits NLRP3 signalling by insoluble activators, such as crystals or particles."

"We previously reported that 1 μM CRID3 abolished LPS-induced IL-1ß secretion from wild-type and Nlrp3 mutant BMDMs, but this concentration was ineffective in inhibiting IL-1ß secretion from LPS+nigericin-stimulated Nlrp3 BMDMs (Vande Walle et al, 2019)."

"Suppression of nigericin stimulated NLRP3 inflammasome signaling by BAPTA and 2-APB can be dissociated from perturbation of Ca 2+ signaling."

"For instance, nigericin-induced NLRP3 activation can be suppressed by PGE2, in a PKA-dependent manner, whereas PGE2-induced suppression of MSU and silica responses is not PKA mediated and thus, may not involve phosphorylation of NLRP3 at S295 (43)."

"We confirmed previously reported observations that pre-treatment of LPS primed myeloid cells with 2-APB prior to stimulation by nigericin (or ATP) completely suppresses all indices of the activated NLRP3 signaling cascade."

"As shown in Figure 2 B, triacsin C treatment significantly inhibited LPS/Nigericin-induced NLRP3 palmitoylation ( Figure 2 B), caspase-1 activation, IL-1β release ( Figure 2 C), and ASC oligomerizatio[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"It indicates acacetin’s inhibition of Nigericin-induced NLRP3 inflammation activation."