Department of Anesthesiology, Nihon University School of Dentistry, Tokyo, Japan.
Division of Immunology and Pathology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
J Periodontal Res. 2021 Jun;56(3):492-500. doi: 10.1111/jre.12849. Epub 2021 Feb 28.
Periodontal pathogens initiate various diseases and induce inflammatory host responses. The activation of inflammasomes triggers caspase-1 and interleukin (IL)-1β-mediated pyroptosis via gasdermin D (GSDMD). Differentiated embryo chondrocyte 2 (Dec2) is a transcription repressor that controls the expression of genes involved in innate immune and inflammatory responses. However, the effects of Dec2 on inflammasome-induced pyroptosis in periodontal tissues remain elusive. This study aimed to characterize the activation of Dec2 inflammasomes that contribute to P. gingivalis lipopolysaccharide (LPS)-induced pyroptosis and its functional and regulatory importance in periodontal inflammation.
Human gingival fibroblasts (HGFs) and human periodontal ligament fibroblasts (HPDLFs) were stimulated with P. gingivalis LPS in vitro. An experimental periodontitis mouse model (wild-type (WT) and Dec2KO) was established to profile periodontal pyroptosis.
The results demonstrate that P. gingivalis LPS activates caspase-1, caspase-11, and NF-κB in HGFs and in HPDLFs. siRNA knockdown of Dec2 stimulated the induction and further upregulated LPS-induced pyroptosis in HGFs and HPDLFs, resulting in the release of IL-1β. Further, a deficiency of Dec2 alleviated periodontal pyroptosis via the transcriptional induction of GSDMD. In addition, P. gingivalis-induced IL-1β expression and Dec2-deficient mice subsequently increased the inflammatory effect of P. gingivalis in HGFs and in HPDLFs, confirming the importance of Dec2 in the activation of inflammasomes and the regulation of pyroptosis.
Our results demonstrate that Dec2 alleviates periodontal pyroptosis by regulating the expression of NF-κB, caspase-1 and GSDMD, suggesting that Dec2 is a crucial component of inflammasome activation and subsequent pyroptosis.
牙周病原体引发多种疾病，并诱导炎症反应。炎症小体的激活通过gasdermin D（GSDMD）触发半胱天冬酶-1（caspase-1）和白细胞介素（IL）-1β介导的细胞焦亡。分化胚胎软骨细胞 2（Dec2）是一种转录抑制因子，控制参与固有免疫和炎症反应的基因的表达。然而，Dec2 对牙周组织中炎症小体诱导的细胞焦亡的影响尚不清楚。本研究旨在描述参与牙龈卟啉单胞菌脂多糖（LPS）诱导的细胞焦亡的 Dec2 炎症小体的激活及其在牙周炎症中的功能和调节作用。
体外刺激人牙龈成纤维细胞（HGFs）和人牙周韧带成纤维细胞（HPDLFs）用牙龈卟啉单胞菌 LPS。建立实验性牙周炎小鼠模型（野生型（WT）和 Dec2KO）以描绘牙周细胞焦亡。
结果表明，牙龈卟啉单胞菌 LPS 在 HGFs 和 HPDLFs 中激活半胱天冬酶-1、半胱天冬酶-11 和 NF-κB。Dec2 的 siRNA 敲低刺激了诱导，并进一步上调了 HGFs 和 HPDLFs 中 LPS 诱导的细胞焦亡，导致 IL-1β的释放。此外，Dec2 缺乏通过 GSDMD 的转录诱导减轻了牙周细胞焦亡。此外，牙龈卟啉单胞菌诱导的 IL-1β表达和 Dec2 缺陷小鼠随后增加了牙龈卟啉单胞菌在 HGFs 和 HPDLFs 中的炎症效应，证实了 Dec2 在炎症小体激活和细胞焦亡调节中的重要性。
我们的结果表明，Dec2 通过调节 NF-κB、半胱天冬酶-1 和 GSDMD 的表达来减轻牙周细胞焦亡，表明 Dec2 是炎症小体激活和随后细胞焦亡的关键组成部分。
