IndraLab

Statements


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"TLR signaling is required for caspase-1 activation induced by SLO and LPS or synthetic lipopeptide but not S. pyogenes infection."

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"Because activation of caspase-1 induced by LPS or lipopeptide and SLO requires TLR signaling, the results suggest that MyD88 and Trif independent activation of the Nlrp3 inflammasome in response to S. pyogenes infection can not be explained by SLO mediated internalization of TLR ligands."

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"However, SLO could promote caspase-1 activation by mediating internalization of microbial molecules distinct of TLR ligands."

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"Consistently, activation of caspase-1 induced by LPS or synthetic lipopeptide in the presence of SLO was impaired in macrophages deficient in Myd88 and Trif (XREF_FIG)."

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"Notably, this activation of caspase-1 mediated by SLO and heat-killed bacteria was abolished in cryopyrin-deficient macrophages ( Figure 6 A)."

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"Consistent with the results obtained with heat-killed bacteria, LPS- and SLO-induced activation of caspase-1 required cryopyrin, but not pannexin-1 ( Figure 6 D)."

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"We tested whether sublytic SLO challenge promotes inflammasome activation by comparing Casp1 activation and HMGB1 secretion in WT, NLRP3 -/-, and Casp1 -/- BMDM treated with sublytic or lytic doses of SLO."

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"We found that in WT BMDM, sublytic SLO doses activated Casp1 and depleted HMGB1 from cell lysates, resulting in extracellular HMGB1 release."

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"SLO also stimulates the activation of NLRP3 and caspase-1 in THP-1 macrophage-like cells (93)."

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"Thus, sublytic SLO can promote HMGB1 release and Casp1 activation in a NLRP3 inflammasome dependent manner."

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"The addition of recombinant SLO to cells exposed to bacterial molecules such as muramyl dipeptide or flagellin can induce the activation of caspase-1."

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"TLR signaling is required for caspase-1 activation induced by SLO and LPS or synthetic lipopeptide but not S. pyogenes infection."

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"Although not required, additional stimulation of bacterial RNA transfected cells with the classical second signals ATP or pore forming bacterial toxins nigericin and SLO enhanced and accelerated caspase-1 activation and release of IL-1beta (XREF_FIG; note decrease in pro-IL-1beta levels due to cleavage)."