Pro-inflammatory cytokine interleukin-6-induced hepcidin, a key mediator of periodontitis-related anemia of inflammation
Pro-inflammatory cytokine interleukin-6-induced hepcidin, a key mediator of periodontitis-related anemia of inflammation
复制标题
促炎细胞因子白细胞介素 6 诱导的铁调素，是牙周炎相关炎症性贫血的关键介质
DOI：
10.1111/jre.12865
复制
发表时间：
2021-03-03
影响因子：
3.5
通讯作者：
Hou, Jianxia
中科院分区：
文献类型：
--
作者：
Han, Ye;Huang, Wenxue;Hou, Jianxia
目的 探讨牙周炎患者是否发生炎症性贫血（AI），并通过实验性牙周炎模型进一步探讨牙周炎相关AI的潜在发病机制。 背景 以往的研究报道牙周炎患者可能表现出AI倾向。然而，牙周炎与AI之间的关系尚不清楚，相关病理机制尚未明确。材料与方法比较98例侵袭性牙周炎（AgP）患者和103名健康受试者的牙周临床参数、炎症标志物和贫血相关指标。通过对小鼠进行结扎来诱导实验性牙周炎模型。检测小鼠炎症标志物、贫血指标、铁调素 mRNA 表达量以及血清铁调素浓度的变化。用白细胞介素-6 (IL-6) 处理人和小鼠肝细胞，根据 mRNA 和蛋白质水平分析铁调素表达的变化。结果 AgP 患者表现出较高的白细胞计数、IL-6 和 C 反应蛋白。调整后的线性回归分析显示 AgP 与血红蛋白 (HGB) 和血细胞比容 (HCT) 下降之间存在相关性。结扎引起的牙周炎引起全身炎症和 IL-6 水平升高。检测到红细胞计数、HGB 和 HCT 降低，而铁调素 mRNA 表达水平和血清铁调素浓度升高。用IL-6处理肝细胞可诱导铁调素mRNA表达和铁调素分泌。结论牙周炎引起的全身炎症导致AI风险增加。 IL-6诱导的铁调素可以发挥核心调节作用并作为关键的病理机制。我们的结果表明牙周炎可能被认为是促进人工智能发展的另一种炎症性疾病。
Objectives To investigate whether anemia of inflammation (AI) occurs in periodontitis patients and to further explore underlying pathogenesis of periodontitis-related AI by an experimental periodontitis model.Background Previous studies have reported periodontitis patients could show a tendency toward AI. However, the relationship between periodontitis and AI remains unclear, and the related pathological mechanisms have not been identified.Materials and Methods Periodontal clinical parameters, inflammatory markers, and anemia-related indicators were compared between 98 aggressive periodontitis (AgP) patients and 103 healthy subjects. An experimental periodontitis model was induced by ligature placement in mice. The changes in mice inflammatory markers, anemia indicators, hepcidin mRNA expression, and serum hepcidin concentrations were measured. Human and mouse liver cells were treated with interleukin-6 (IL-6) for analyzing the changes in hepcidin expression based on mRNA and protein levels.Results AgP patients exhibited higher white blood cell counts, IL-6, and C-reactive protein. Adjusted linear regression analyses showed correlations between AgP and decreased hemoglobin (HGB) and hematocrit (HCT). The ligature-induced periodontitis caused systemic inflammation and elevated IL-6 levels. Lower red blood cell counts, HGB, and HCT were detected, whereas the levels of hepcidin mRNA expression and serum hepcidin concentrations increased. The treatment of hepatocytes with IL-6 induced both hepcidin mRNA expression and hepcidin secretion.Conclusions Systemic inflammation induced by periodontitis leads to an increased risk for AI. IL-6-induced hepcidin could play a central mediator role and act as a key pathologic mechanism. Our results demonstrate periodontitis may be considered as an additional inflammatory disease contributing to the development of AI.