State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Biochim Biophys Acta Mol Basis Dis. 2018 Jan;1864(1):226-237. doi: 10.1016/j.bbadis.2017.10.025. Epub 2017 Oct 21.
Apical periodontitis (AP) is an inflammation affecting the periapical region of tooth root. Microbial pathogens activate inflammasomes and promote the production of pro-inflammatory cytokines. Caspase-1-mediated pyroptosis is a possible mechanism involved in the initiation and progression of AP. The purpose of this study was to evaluate the role of caspase-1 and pyroptosis on AP at different stages. Human periapical inflammatory tissue was collected to study chronic AP stage. Human periodontal ligament fibroblasts (hPDLFs) were stimulated with lipopolysaccharide in vitro for 24h to simulate early AP stage. Experimental AP rat model was established to study acute AP stage from 0d to 28d. The results showed that NLRP3, cleaved caspase-1 and Interleukin (IL)-1β were enhanced in all AP stages. Caspase-1 activation was detectable in most cells. However, the level of pyroptosis was in accordance with the degree of AP inflammation. Early and chronic AP showed a comparable hemostasis state, with pyroptosis remaining in a reduced level. On the contrary, extensive pyroptosis accelerated inflammation and induced cell death in acute AP. VX765, a caspase-1 inhibitor, was used in an experimental AP rat model. The results showed that VX765 suppressed bone loss, suggesting a role of pyroptosis on bone resorption in acute AP. VX765 also inhibited the expressions of IL-1β, Monocyte chemoattractant protein-1 (MCP-1), IL-6 and IL-8 in vitro, thus decreased inflammatory responses during AP. In conclusion, caspase-1 and pyroptosis contributed to AP inflammation and lesion and pyroptosis extent was in line with AP progression.
根尖周炎（AP）是一种影响牙根根尖区域的炎症。微生物病原体激活炎性体并促进促炎细胞因子的产生。半胱天冬酶-1 介导的细胞焦亡是参与 AP 起始和进展的可能机制。本研究旨在评估 caspase-1 和细胞焦亡在不同 AP 阶段的作用。收集人根尖炎性组织研究慢性 AP 期。体外用人牙周膜成纤维细胞（hPDLFs）用脂多糖刺激 24h 模拟早期 AP 期。建立急性 AP 大鼠模型从 0d 到 28d 研究急性 AP 期。结果表明，NLRP3、裂解的半胱天冬酶-1 和白细胞介素（IL）-1β在所有 AP 期均增强。在大多数细胞中可检测到半胱天冬酶-1 的激活。然而，细胞焦亡的水平与 AP 炎症的程度一致。早期和慢性 AP 显示出相似的止血状态，细胞焦亡保持在较低水平。相反，广泛的细胞焦亡加速了急性 AP 的炎症并诱导细胞死亡。在急性 AP 大鼠模型中使用半胱天冬酶-1 抑制剂 VX765。结果表明，VX765 抑制了骨丢失，提示细胞焦亡在急性 AP 中的骨吸收作用。VX765 还抑制了体外 IL-1β、单核细胞趋化蛋白-1（MCP-1）、IL-6 和 IL-8 的表达，从而减轻了 AP 期间的炎症反应。总之，半胱天冬酶-1 和细胞焦亡参与了 AP 炎症和病变，细胞焦亡的程度与 AP 的进展一致。
