Inflammasomes cleave and activate interleukin- (IL-) 1β and IL-18 which have both shared and unique biological functions. IL-1β is an important mediator of the acute phase response to infections and tissue damage, whereas IL-18 takes part in activation and tailoring of the adaptive immune response. While IL-1β has served as the prototypic indicator of inflammasome activation, few studies have compared the potential differences in IL-1β and IL-18 production during inflammasome activation. Since these cytokines partake in different immune pathways, the involvement of inflammasome activity in different conditions needs to be described beyond IL-1β production alone. To address a potential heterogeneity in inflammasome functionality, ATP, chitosan, or silica oxide (SiO₂) were used to induce NLRP3 inflammasome activation in THP-1 cells and the subsequent outcomes were quantified. Despite using doses of the inflammasome inducers yielding similar release of IL-1β, SiO₂-stimulated cells showed a lower concentration of released IL-18 compared to ATP and chitosan. Hence, the cells stimulated with SiO₂ responded with a distinctly different IL-18 : IL-1β ratio. The difference in the IL-18 : IL-1β ratio for SiO₂ was constant over different doses. While all downstream responses were strictly dependent on a functional NLRP3 inflammasome, the differences did not depend on the level of gene expression, caspase-1 activity, or pyroptosis. We suggest that the NLRP3 inflammasome response should be considered a dynamic process, which can be described by taking the ratio between IL-1β and IL-18 into account and moving away from an on/off perspective of inflammasome activation.

中文翻译：

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分子上不同的 NLRP3 诱导剂介导来自人单核细胞的白细胞介素 1β 和白细胞介素 18 的不同比率

炎症小体切割并激活具有共同和独特生物学功能的白细胞介素- (IL-) 1 β和 IL-18。IL-1 β是对感染和组织损伤的急性期反应的重要介质，而 IL-18 参与适应性免疫反应的激活和调整。虽然 IL-1 β已作为炎症小体激活的原型指标，但很少有研究比较炎症小体激活过程中 IL-1 β和 IL-18 产生的潜在差异。由于这些细胞因子参与不同的免疫途径，炎症小体活动在不同条件下的参与需要在 IL-1 β之外进行描述单独生产。为了解决炎性体功能的潜在异质性，使用 ATP、壳聚糖或氧化硅 (SiO ₂ ) 在 THP-1 细胞中诱导 NLRP3 炎性体活化，并量化随后的结果。尽管使用不同剂量的炎性体诱导剂产生类似的 IL-1 β释放，但与 ATP 和壳聚糖相比，SiO ₂刺激的细胞显示出较低浓度的 IL-18 释放。因此，用 SiO ₂刺激的细胞以明显不同的 IL-18 : IL-1 β比率作出反应。IL-18 : IL-1 β比值对于 SiO ₂的差异在不同剂量下是恒定的。虽然所有下游反应都严格依赖于功能性 NLRP3 炎症小体，但差异并不取决于基因表达水平、caspase-1 活性或细胞焦亡。我们建议 NLRP3 炎症小体反应应被视为一个动态过程，可以通过考虑 IL-1 β和 IL-18之间的比率并远离炎症小体激活的开/关角度来描述。