Excess adipose tissue (AT) associates with inflammation and obesity-related diseases. We studied whether calcium-sensing receptor (CaSR)-mediated NLRP3 inflammasome activation in THP-1 macrophages elevates inflammation in LS14 preadipocytes, modeling deleterious AT cell crosstalk. THP-1 macrophages exposed to cinacalcet (CaSR activator, 2 μM, 4 h) showed elevated proinflammatory marker and NLRP3 inflammasome mRNA, pro-IL-1β protein and caspase-1 activity, whereas preincubation with CaSR negative modulators prevented these effects. The key NLRP3 inflammasome component ASC was silenced (siRNA) in THP-1 cells, and inflammasome activation was evaluated (qPCR, Western blot, caspase-1 activity) or they were further cultured to obtain conditioned medium (CoM). Exposure of LS14 preadipocytes to CoM from cinacalcet-treated THP-1 elevated LS14 proinflammatory cytokine expression, which was abrogated by THP-1 inflammasome silencing. Thus, CaSR activation elevates THP-1-induced inflammation in LS14 preadipocytes, via macrophage NLRP3 inflammasome activation. Modulating CaSR activation may prevent deleterious proinflammatory cell crosstalk in AT, a promising approach in obesity-related metabolic disorders.

中文翻译：

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THP-1巨噬细胞中的钙感应受体激活会触发NLRP3炎性小体和人脂肪细胞的炎症。

过多的脂肪组织（AT）与炎症和肥胖相关疾病有关。我们研究了THP-1巨噬细胞中钙敏感受体（CaSR）介导的NLRP3炎性小体激活是否会加剧LS14前脂肪细胞的炎症，从而模拟有害的AT细胞串扰。暴露于cinacalcet（CaSR激活剂，2μM，4 h）的THP-1巨噬细胞显示出较高的促炎标记和NLRP3炎性体mRNA，pro-IL-1β蛋白和caspase-1活性，而与CaSR负调节剂一起预孵育阻止了这些作用。在THP-1细胞中沉默关键的NLRP3炎性体成分ASC（siRNA），评估炎性体激活（qPCR，Western印迹，caspase-1活性）或进一步培养以获得条件培养基（CoM）。通过cinacalcet处理的THP-1将LS14前脂肪细胞暴露于CoM会提高LS14促炎细胞因子的表达，这种表达已被THP-1炎症小体沉默所消除。因此，CaSR激活通过巨噬细胞NLRP3炎性体激活，提高了LS14前脂肪细胞中THP-1诱导的炎症。调节CaSR激活可以预防AT中有害的促炎细胞串扰，这是肥胖相关代谢性疾病的一种有前途的方法。