State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
Front Cell Infect Microbiol. 2017 Nov 14;7:474. doi: 10.3389/fcimb.2017.00474. eCollection 2017.
Periodontitis is defined as inflammation affecting the supporting tissue of teeth. Periodontal pathogens initiate the disease and induce inflammatory host response. Hypoxia may accelerate the process by producing pro-inflammatory factors. The aim of this study is to investigate the effect of () lipopolysaccharides (LPS) and () LPS in inducing caspase-1 activation in normoxic or hypoxic phases. The results showed that healthy gingiva was in a normoxic phase (HIF-1α negative). However, hypoxia appeared in periodontitis, in which NLRP3, cleaved-caspase-1, interleukin 1 beta (IL-1β) and caspase-1-induced cell death was enhanced in periodontitis specimens. The experiment showed that LPS slightly decreased the level of NLRP3 and IL-1β in gingival fibroblasts under normoxia. Surprisingly, hypoxia reversed the effects of LPS, highly promoted caspase-1 activation and IL-1β maturation. LPS, a kind of pathogen-associated molecular pattern (PAMP) was chosen to simulate the effect of Gram-negative microbiota. Different from LPS, LPS enhanced IL-1β maturation both in normoxia and hypoxia. Moreover, LPS turned normoxia into hypoxia phase in experimental periodontitis model, which may subsequently propel the inflammatory effect of LPS. It was concluded that LPS induced a hypoxic phase, which is a combing pathological factor of LPS in caspase-1 activating and IL-1β maturation in periodontal inflammation.
牙周炎被定义为影响牙齿支持组织的炎症。牙周病原体引发疾病并诱导炎症宿主反应。缺氧可能通过产生促炎因子加速这一过程。本研究旨在探讨（）脂多糖（LPS）和（）LPS 在诱导正常氧或缺氧阶段 caspase-1 激活中的作用。结果表明，健康牙龈处于正常氧阶段（HIF-1α 阴性）。然而，在牙周炎中出现了缺氧，其中 NLRP3、切割的 caspase-1、白细胞介素 1β（IL-1β）和 caspase-1 诱导的细胞死亡在牙周炎标本中增强。实验表明，LPS 在正常氧条件下轻度降低牙龈成纤维细胞中 NLRP3 和 IL-1β 的水平。令人惊讶的是，缺氧逆转了 LPS 的作用，高度促进 caspase-1 激活和 IL-1β 成熟。LPS 是一种病原体相关分子模式（PAMP），用于模拟革兰氏阴性微生物群的作用。与 LPS 不同，LPS 增强了正常氧和缺氧条件下的 IL-1β 成熟。此外，LPS 在实验性牙周炎模型中将正常氧转变为缺氧阶段，这可能随后推动 LPS 的炎症作用。结论是，LPS 诱导了缺氧阶段，这是 LPS 在 caspase-1 激活和牙周炎中 IL-1β 成熟中的一种联合病理因素。
