1 Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.
2 Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
J Dent Res. 2018 Nov;97(12):1391-1398. doi: 10.1177/0022034518775036. Epub 2018 May 23.
NLRP6, a member of the nucleotide-binding domain, leucine-rich repeat-containing (NLR) innate immune receptor family, has been reported to participate in inflammasome formation. Activation of inflammasome triggers a caspase-1-dependent programming cell death called pyroptosis. However, whether NLRP6 induces pyroptosis has not been investigated. In this study, we showed that NLRP6 overexpression activated caspase-1 and gasdermin-D and then induced pyroptosis of human gingival fibroblasts, resulting in release of proinflammatory mediators interleukin (IL)-1β and IL-18. Moreover, NLRP6 was highly expressed in gingival tissue of periodontitis compared with healthy controls. Porphyromonas gingivalis, which is a commensal bacterium and has periodontopathic potential, induced pyroptosis of gingival fibroblasts by activation of NLRP6. Together, we, for the first time, identified that NLRP6 could induce pyroptosis of gingival fibroblasts by activation of caspase-1 and may play a role in periodontitis.
NLRP6 是核苷酸结合域富含亮氨酸重复（NLR）先天免疫受体家族的成员，据报道它参与了炎症小体的形成。炎症小体的激活触发了一种称为细胞焦亡的 caspase-1 依赖性程序性细胞死亡。然而，NLRP6 是否诱导细胞焦亡尚未被研究。在这项研究中，我们表明 NLRP6 的过表达激活了 caspase-1 和 gasdermin-D，然后诱导人牙龈成纤维细胞发生细胞焦亡，导致促炎介质白细胞介素（IL）-1β和 IL-18 的释放。此外，与健康对照组相比，NLRP6 在牙周炎的牙龈组织中高表达。牙龈卟啉单胞菌是一种共生菌，具有牙周病的潜力，它通过激活 NLRP6 诱导牙龈成纤维细胞发生细胞焦亡。总之，我们首次发现 NLRP6 通过激活 caspase-1 诱导牙龈成纤维细胞发生细胞焦亡，并可能在牙周炎中发挥作用。
