目的：基于白介素（IL）-37信号通路探讨口腔黏膜免疫稳态的机制。方法：通过牙龈绦虫感染后人巨噬细胞诱导的口腔炎症模型,在C57BL/6J小鼠中建立实验性牙周炎模型,分为对照组和rhIL-37b组。qPCR检测IL-37、炎症因子IL-6,肿瘤坏死因子（TNF）-α、IL-10和IL-1β和核转录因子（NF）-κB通路,蛋白印迹检测IL-37和NF-κB通路的表达。微电脑断层扫描（微CT）成像用于确定骨质流失。结果：THP-1细胞在牙龈绦虫感染后显示出IL-37 mRNA表达增高,与对照组相比,rhIL-37b处理的细胞显示牙龈绦虫感染后人巨噬细胞的IL-6、TNF-α和IL-1β的产生减少,IκBα降解增加,磷酸化的p65水平降低。在小鼠牙周炎模型rhIL-37b组牙龈炎症和骨质流失降低,差异有统计学意义。结论：IL-37通过抑制NF-κB信号通路来调节牙周炎的炎性细胞因子反应,降低了牙龈组织骨质流失和细胞因子表达。
Abstract
Objective This study aims to elucidate the mechanism behind oral mucosal immune homeostasis by investigating the IL-37 signaling pathway. Methods An experimental model of oral inflammation was established in C57BL/6J mice through gingival nematode infection and induction of oral inflammation by human macrophages. The mice were categorized into control and rhIL-37b treatment groups. IL-37, inflammatory cytokines (IL-6, TNF-α, IL-10, IL-1β), and the NF-κB pathway were assessed using qPCR. Western blotting was employed to analyze the protein expression of IL-37 and the NF-κB pathway. Micro-computed tomography (microCT) imaging was utilized to quantify bone loss. Results Following gingival nematode infection, THP-1 cells exhibited elevated IL-37 mRNA expression. In human macrophages treated with rhIL-37b, production of IL-6, TNF-α, and IL-1β was reduced, accompanied by enhanced degradation of IκBα and diminished levels of phosphorylated p65 after gingival nematode infection, as compared to the control group. In the mouse periodontitis model, the rhIL-37b-treated group demonstrated a significant reduction in gingival inflammation and bone loss. Conclusion IL-37 plays a regulatory role in the inflammatory cytokine response of periodontitis by inhibiting the NF-κB signaling pathway. Consequently, IL-37 contributes to the mitigation of gingival tissue bone loss and cytokine expression.
关键词
IL-37 /
口腔黏膜免疫稳态 /
牙周炎 /
NF-κB
Key words
IL-37 /
oral mucosal immune homeostasis /
periodontitis /
NF-κB
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基金
江苏省卫生健康委员会科研项目（20210435）
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