Novel inflammatory pathways in periodontitis.
Novel inflammatory pathways in periodontitis.
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DOI：
10.1177/0022034514526240
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发表时间：
2014-05-01
影响因子：
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通讯作者：
Sahingur, S E
中科院分区：
文献类型：
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作者：
Hajishengallis, G;Sahingur, S E
对参与调节牙周炎和牙槽骨丢失的生物学机制的新见解正在为牙周炎的新治疗策略铺平道路。中性粒细胞黏附级联反应在感染或炎症反应中的转运是免疫中的一个关键范例。发育内皮细胞基因座-1(Del-1)是新近发现的多种内源性白细胞黏附级联抑制因子之一。DEL-1与内皮细胞上的细胞间黏附分子-1(ICAM-1)竞争结合中性粒细胞上的LFA-1整合素，从而调节中性粒细胞的募集和局部炎症。在动物牙周炎模型中，Del-1缺乏导致严重的炎症和牙槽骨丢失，但局部应用重组Del-1可防止中性粒细胞渗入和骨丢失。促炎症细胞因子IL-17抑制Del-1的表达。核酸受体介导的炎症反应可能在牙周病的发病机制中起重要作用。炎症过程中释放的细菌核酸被宿主微生物DNA传感器检测到，例如Toll样受体-9(TLR-9)，导致激活促炎和/或抗炎信号通路。来自牙周炎相关细菌的DNA通过TLR-9和NF-kappaB信号通路诱导人巨噬细胞样细胞产生促炎细胞因子，但对人成骨细胞的影响较小。抑制人巨噬细胞中的TLR-9信号减少了对牙龈假单胞菌DNA的反应产生的细胞因子。在慢性牙周炎中，TLR-9基因启动子区域的一个多态位点的差异表达和TLR-9基因和蛋白表达的增加被报道。进一步的研究证实牙周细菌DNA有助于体内破坏性炎症，可能为控制牙周炎提供替代的治疗靶点。
New insights into the biological mechanisms involved in modulating periodontal inflammation and alveolar bone loss are paving the way for novel therapeutic strategies for periodontitis. The neutrophil adhesion cascade for transmigration in response to infection or inflammation is a key paradigm in immunity. Developmental endothelial locus-1 (Del-1) is one of several newly identified endogenous inhibitors of the leukocyte adhesion cascade. Del-1 competes with intercellular adhesion molecule-1 (ICAM-1) on endothelial cells for binding to the LFA-1 integrin on neutrophils, thereby regulating neutrophil recruitment and local inflammation. In animal periodontitis models, Del-1 deficiency resulted in severe inflammation and alveolar bone loss, but local treatment with recombinant Del-1 prevented neutrophil infiltration and bone loss. The expression of Del-1 is inhibited by the pro-inflammatory cytokine IL-17. Nucleic-acid-receptor-mediated inflammatory responses may be important in periodontal disease pathogenesis. Bacterial nucleic acids released during inflammation are detected by host microbial DNA sensors, e.g., Toll-like receptor-9 (TLR-9), leading to the activation of pro- and/or anti-inflammatory signaling pathways. DNA from periodontitis-associated bacteria induced pro-inflammatory cytokine production in human macrophage-like cells through the TLR-9 and NF-kappaB signaling pathways, but had less effect on human osteoblasts. Inhibition of TLR-9 signaling in human macrophages reduced cytokine production in response to P. gingivalis DNA. Differential expression of a polymorphic site in the TLR-9 gene promoter region and increased TLR-9 gene and protein expression were reported in chronic periodontitis. Further research to confirm that periodontal bacterial DNA contributes to destructive inflammation in vivo could provide alternative therapeutic targets to control periodontitis.