Association of pocket epithelial cell proliferation in periodontitis with TLR9 expression and inflammatory response

Association of pocket epithelial cell proliferation in periodontitis with TLR9 expression and inflammatory response
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DOI:
10.1016/j.jfma.2012.07.043
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发表时间:
2014-08-01
影响因子:
3.2
通讯作者:
Ku, Chia-Chi
Ku, Chia-Chi
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Yen-Chun;Liu, Cheing-Meei;Ku, Chia-Chi

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背景/目的:炎症反应是由Toll样受体(TLRs)和核苷酸寡聚化结构域(NOD)样受体(NLRs)等先天受体识别微生物配体后触发的。在这项研究中,我们通过免疫组织化学的方法检测了牙周炎或牙周炎患者的连续冰冻切片,分析了所选择的先天受体在临床健康和病变牙龈组织中的表达模式及其与细胞增殖的关系。方法:共19例患者的牙龈活检标本均来自国立台湾大学医学中心牙科学院,并经知情同意。在使用牙龈指数进行临床评估后,样本被分配到牙周炎组或牙周炎组。冰冻切片行苏木精-伊红染色进行组织学评价。用一组抗体对同一样本的连续切片进行免疫组织化学分析。结果:细胞角蛋白19(CK19)在口腔上皮基底膜和囊袋上皮各层的表达均明显增强,导致槽状上皮细胞明显增殖和向牙周炎组织固有层迁移。无论疾病状态如何,TLR4和胞浆NLRP3在所有切片中均有表达。但TLR9、CK19、胶原降解基质金属蛋白酶13和活化的核因子-kappaB亚单位p65在牙周炎组织中的表达高于牙周炎组织。结论:TLR9信号通路的激活与牙周炎密切相关,可能与牙周组织的完整性丧失有关。进一步研究TLR9信号在牙周上皮细胞中被激活的机制可能会导致治疗牙周炎的新策略。版权所有(C)2012,爱思唯尔台湾有限责任公司及台湾医学会。版权所有。
Background/Purpose: Inflammatory response is triggered after recognition of microbial ligands by innate receptors such as Toll-like receptors (TLRs) and Nucleotide oligomerization domain (NOD)-like receptors (NLRs). In this study, we examined serial frozen sections of gingival biopsies from patients with gingivitis or periodontitis by immunohistochemical analysis for the topographic expression patterns of selected innate receptors and their association with cell proliferation in clinically healthy and diseased gingival tissues.Methods: A total of 19 gingival biopsies were collected from patients at the School of Dentistry, National Taiwan University Medical Center according to approved protocol and with informed consent. The specimens were assigned to either the gingivitis group or periodontitis group after clinical evaluation using gingival index. Frozen sections of gingival biopsies were stained with hematoxylin and eosin for histological evaluation. Serial sections of the same samples were stained with a panel of antibodies for immunohistochemical analysis. Expression of each protein marker was compared in the oral versus the sulcular epithelium of the same section.Results: Expression of cytokeratin 19 (CK19) was markedly increased in the basement membranes of the oral epithelium and in all layers of the pocket epithelium where it caused evident cell proliferation and migration of sulcular epithelial cells into the lamina propria of periodontitis tissue. TLR4 and the cytoplasmic NLRP3 were expressed in all sections examined regardless of disease state. However, expression of TLR9-, CK19- and collagenolytic matrix metalloproteinase-13 and activated NF-kappa B subunit p65 was more commonly found in periodontitis tissues than in gingivitis tissues.Conclusion: Activation of TLR9 signaling in the pocket epithelium was highly associated with periodontal inflammation and possibly with loss of tissue integrity. Further studies of mechanisms by which TLR9 signaling is activated in the periodontal epithelium may lead to new strategies for treating periodontitis. Copyright (C) 2012, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.