The Role of Immune Regulatory Mechanisms in the Pathogenesis of Periapical Periodontitis

免疫调节机制在根尖周炎发病机制中的作用

• 批准号: 10470405
• 负责人: SHIMAUCHI Hidetoshi
• 金额: $ 4.86万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470405/
• 关键词: periapical periodontitis; pro-inflammatory cytokine; anti-inflammatory cytokine; superoxide; nitric oxide; growth factor; LPS-tolerance; cyclooxygenase-2; 根尖性歯周病; 活性酸素; プロスタグランディン合成; 調節性サイトカイン; 慢性化; 免疫応答制御機構; 根管浸出液; IL-1β; IL-1ra; 単球; マク

Chronic periapical periodontitis is a chronic destructive disease characterized by an interaction of bacteria infected in the root canal system and the host immune cells. The local host response results in the release of wide array of the pro-and anti-inflammatory cytokines and mediators in the periapical lesion. We quantified the levels of IL-1β and IL-1ra in periapical exudates, and indicated that IL-1ra-mediated antagonism occurred to block locally produced IL-1 activity. Decreased IL-1ra : IL-1β ratio resulted in an acute and higher inflammatory activity in periapical lesion. Our quantitative analysis also revealed increased IL-8 production in the periapical exudate from symptomatic periapical lesion. A significantly positive correlation was found between IL-8 and nitric oxide levels. Semi-quantitative RT-PCR analysis was performed to determine the expression of pro- and anti-inflammatory cytokine and growth factor messages in the periapical tissue specimen. Results showed that COX … More -2 and IL-8 messages were present in all samples tested, and suggested up-regulated production of pro-inflammatory mediators in periapical lesions. On the other hand, anti-inflammatory cytokines, IL-10 and TGF-β1 mRNA was detected in most samples. We also showed the presence of IGF-1 and EGF messages in the majority of test specimens. In vitro studies also revealed that the chronic exposure of human monocytes to Porphyromonas gingivalis LPS resulted in the induction of LPS tolerance that resulted in the selective up-or down-regulation of cell functions. Our data also suggested that IL-10 mediate IL-6 down-regulation in P. gingivalis LPS-tolerant monocytes in an autocrine manner. These results suggest the potential involvement of both the pro-and anti-inflammatory cytokines and mediators in the regulation of chronic inflammatory disease periapical periodontitis. In conclusion, dissection of the precise role of these cytokines and mediators that have an impact on perapical pathogenesis may provide opportunities for the development of new diagnostic procedures and therapeutic agents. Less

慢性根尖周炎是一种慢性破坏性疾病，其特征是根管系统中感染的细菌与宿主免疫细胞相互作用。局部宿主反应导致根尖周病变释放大量促炎和抗炎细胞因子和介质。我们定量了根尖周渗出液中 IL-1β 和 IL-1ra 的水平，并表明 IL-1ra 介导的拮抗作用阻止了局部产生的 IL-1 活性。 IL-1ra : IL-1β 比率降低导致根尖周病变急性且较高的炎症活动。我们的定量分析还显示，有症状的根尖周病变的根尖周渗出液中 IL-8 的产生增加。 IL-8 和一氧化氮水平之间存在显着正相关。进行半定量 RT-PCR 分析以确定根尖周组织标本中促炎和抗炎细胞因子和生长因子信息的表达。结果显示，所有测试样本中均存在 COX … 更多 -2 和 IL-8 信息，并表明根尖周病变中促炎介质的产生上调。另一方面，在大多数样品中检测到抗炎细胞因子、IL-10 和 TGF-β1 mRNA。我们还在大多数测试样本中显示了 IGF-1 和 EGF 信息的存在。体外研究还表明，人类单核细胞长期暴露于牙龈卟啉单胞菌 LPS 会导致 LPS 耐受性的诱导，从而导致细胞功能选择性上调或下调。我们的数据还表明，IL-10 以自分泌方式介导牙龈卟啉单胞菌 LPS 耐受性单核细胞中 IL-6 的下调。这些结果表明促炎和抗炎细胞因子和介质可能参与慢性炎症性疾病根尖周炎的调节。总之，剖析这些影响根尖部发病机制的细胞因子和介质的精确作用可能为开发新的诊断程序和治疗药物提供机会。较少的

项目成果

Shinmauchi H, Ogawa T, Hayashi T, Okuda K, Okada H.: "Induction of tolerance to Porphyromonas gingivalis LPS in human onocytes (in Japanese)"Jpn. J. Inflammation. 20(1) (in press). (2000)

Shinmauchi H、Okawa T、Hayashi T、Okuda K、Okada H.：“在人单核细胞中诱导牙龈卟啉单胞菌 LPS 耐受性（日语）”Jpn。

Shimauchi H: "Balance of Interleukin-1β and Interleukin-1 receptor antaonist in human periapical lesions"Journal of Endodontics. 20(2). 116-119

Shimauchi H：“人根尖病变中白细胞介素 1β 和白细胞介素 1 受体拮抗剂的平衡”《牙髓学杂志》20(2)。

Shimauchi H.et.al.: "An Autoregulatory Effect of Interleukin-10 on Proinflammatory Cytokine Production by Porphyromonas gingivalis Lipopolysaccharide-Tolerant Human Monocytes" Infection and Immunity. Vol.67(5)(印刷中). (1999)

Shimauchi H.et.al.：“Interleukin-10 对牙龈卟啉单胞菌脂多糖耐受性人单核细胞产生促炎细胞因子的自动调节作用”感染和免疫，第 67 卷（5）（出版中）。

Shimauchi H: "Autoreguratory effect of Interleukin-10 on proinflamatory cytokine production by Porphyromonas gingivalis lipopolysaccharide-tolerant huma monocytes"Infection and Immunity. 67(5). 2153-2159

Shimauchi H：“白细胞介素 10 对牙龈卟啉单胞菌脂多糖耐受的人单核细胞产生促炎细胞因子的自动调节作用”感染和免疫。

Shimauchi H, Takayama S, Imai-Tanaka T, Okada H.: "Balance of interleukin-1 β and interleukin-1 receptor antagonist in human periapical lesions."J. Endodon. 24(2). 116-9 (1998)

Shimauchi H、Takayama S、Imai-Tanaka T、Okada H.：“人根尖损伤中白细胞介素 1 β 和白细胞介素 1 受体拮抗剂的平衡”，J. Endodon 24(2)。