He Dawei, Li Xiaoyan, Zhang Fengzhu, Wang Chen, Liu Yi, Bhawal Ujjal K, Sun Jiang
Department of Periodontics and Oral Mucosa Disease, Dalian Stomatological Hospital, Dalian, China.
Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
J Periodontal Implant Sci. 2022 Feb;52(1):28-38. doi: 10.5051/jpis.2101380069.
Macrophages play crucial roles as early responders to bacterial pathogens and promote/ or impede chronic inflammation in various tissues. Periodontal macrophage-induced pyroptosis results in physiological and pathological inflammatory responses. The transcription factor Dec2 is involved in regulating immune function and inflammatory processes. To characterize the potential unknown role of Dec2 in the innate immune system, we sought to elucidate the mechanism that may alleviate macrophage pyroptosis in periodontal inflammation.
lipopolysaccharide (LPS) was used to induce pyroptosis in RAW 264.7 macrophages. Subsequently, we established an LPS-stimulated Dec2 overexpression cellular model in macrophages. Human chronic periodontitis tissues were employed to evaluate potential changes in inflammatory marker expression and pyroptosis. Finally, the effects of Dec2 deficiency on inflammation and pyroptosis were characterized in a -treated experimental periodontitis -knockout mouse model.
Macrophages treated with LPS revealed significantly increased messenger RNA expression levels of Dec2 and interleukin (IL)-1β. Dec2 overexpression reduced IL-1β expression in macrophages treated with LPS. Overexpression of Dec2 also repressed the cleavage of gasdermin D (GSDMD), and the expression of caspase-11 was concurrently reduced in macrophages treated with LPS. Human chronic periodontitis tissues showed significantly higher gingival inflammation and pyroptosis-related protein expression than non-periodontitis tissues. , -challenged mice exhibited a significant augmentation of F4/80, tumor necrosis factor-α, and IL-1β. Dec2 deficiency markedly induced GSDMD expression in the periodontal ligament of -challenged mice.
Our findings indicate that Dec2 deficiency exacerbated LPS-induced periodontal inflammation and GSDMD-mediated pyroptosis. Collectively, our results present novel insights into the molecular functions of macrophage pyroptosis and document an unforeseen role of Dec2 in pyroptosis.
巨噬细胞作为细菌病原体的早期应答者发挥着关键作用，并促进或阻碍各种组织中的慢性炎症。牙周巨噬细胞诱导的细胞焦亡会导致生理和病理炎症反应。转录因子Dec2参与调节免疫功能和炎症过程。为了阐明Dec2在先天免疫系统中潜在的未知作用，我们试图阐明可能减轻牙周炎症中巨噬细胞焦亡的机制。
使用脂多糖（LPS）诱导RAW 264.7巨噬细胞发生细胞焦亡。随后，我们在巨噬细胞中建立了LPS刺激的Dec2过表达细胞模型。用人慢性牙周炎组织评估炎症标志物表达和细胞焦亡的潜在变化。最后，在经治疗的实验性牙周炎敲除小鼠模型中表征Dec2缺陷对炎症和细胞焦亡的影响。
用LPS处理的巨噬细胞显示Dec2和白细胞介素（IL）-1β的信使RNA表达水平显著增加。Dec2过表达降低了用LPS处理的巨噬细胞中IL-1β的表达。Dec2的过表达还抑制了gasdermin D（GSDMD）的切割，并且在用LPS处理的巨噬细胞中caspase-11的表达同时降低。人慢性牙周炎组织显示牙龈炎症和细胞焦亡相关蛋白表达显著高于非牙周炎组织。经LPS攻击的小鼠表现出F4/80、肿瘤坏死因子-α和IL-1β的显著增加。Dec2缺陷显著诱导了经LPS攻击的小鼠牙周膜中GSDMD的表达。
我们的研究结果表明，Dec2缺陷加剧了LPS诱导的牙周炎症和GSDMD介导的细胞焦亡。总体而言，我们的结果为巨噬细胞焦亡的分子功能提供了新的见解，并记录了Dec2在细胞焦亡中意想不到的作用。
