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首页> 外文期刊>Cell and Tissue Research >Activation of the NLRP3/caspase-1 inflammasome in human dental pulp tissue and human dental pulp fibroblasts
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Activation of the NLRP3/caspase-1 inflammasome in human dental pulp tissue and human dental pulp fibroblasts

机译：NLRP3 / caspase-1炎性小体在人牙髓组织和人牙髓成纤维细胞中的活化

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摘要

The NLRP3/caspase-1 inflammasome pathway plays an important role in cellular immune defence against bacterial infection; however, its function in human dental pulp tissue and human dental pulp fibroblasts remains poorly understood. We demonstrate that NLRP3 protein expression occurs to a greater extent in pulp tissue with irreversible pulpitis than in normal pulp tissue and in tissue with reversible pulpitis. Caspase-1 is present in its active (cleaved) form only in pulp tissue with irreversible pulpitis. NLRP3 and caspase-1 are expressed in the odontoblast layers in normal human dental pulp tissue, whereas in inflamed pulp tissue, the odontoblast layers are disrupted and dental pulp cells are positive for NLRP3 and caspase-1. Additionally, we investigate the role of the NLRP3/caspase-1 inflammasome pathway in human dental pulp fibroblasts and show that ATP activates the P2X7 receptor on the cell membrane triggering K+ efflux and inducing the gradual recruitment of the membrane pore pannexin-1. Extracellular lipopolysaccharide is able to penetrate the cytosol and activate NLRP3. Furthermore, the low intracellular K+ concentration in the cytosol triggers reactive oxygen species generation, which also induces the NLRP3 inflammasome. Thus, the NLRP3/caspase-1 pathway has a biological role in the innate immune response mounted by human dental pulp fibroblasts.
机译：NLRP3 / caspase-1炎性体途径在细胞抵抗细菌感染的免疫防御中起着重要作用。然而，其在人类牙髓组织和人类牙髓成纤维细胞中的功能仍知之甚少。我们证明与正常牙髓组织和可逆性牙髓炎组织相比，NLRP3蛋白表达在不可逆性牙髓炎的牙髓组织中发生的程度更大。 Caspase-1以其活性（裂解）形式仅存在于具有不可逆性牙髓炎的牙髓组织中。 NLRP3和caspase-1在正常人牙髓组织的成牙本质细胞层中表达，而在发炎的牙髓组织中，成牙本质细胞层被破坏，牙髓细胞对NLRP3和caspase-1呈阳性。此外，我们调查了NLRP3 / caspase-1炎性小体通路在人牙髓成纤维细胞中的作用，并显示ATP激活了细胞膜上的P2X7受体，触发K +外排并诱导膜孔pannexin-1的逐渐募集。细胞外脂多糖能够穿透细胞质并激活NLRP3。此外，胞浆中低的细胞内K +浓度会触发活性氧的产生，这也会诱导NLRP3炎性体。因此，NLRP3 / caspase-1途径在人类牙髓成纤维细胞固有的免疫应答中具有生物学作用。

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