Expression and regulation of the NALP3 inflammasome complex in periodontal diseases
Expression and regulation of the NALP3 inflammasome complex in periodontal diseases
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DOI：
10.1111/j.1365-2249.2009.03972.x
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发表时间：
2009-09-01
影响因子：
4.6
通讯作者：
Belibasakis, G. N.
中科院分区：
文献类型：
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作者：
Bostanci, N.;Emingil, G.;Belibasakis, G. N.
牙周炎是一种感染过程，其特征是炎症影响牙齿的支撑结构。牙龈卟啉单胞菌是一种与牙周炎发病有关的主要口腔细菌。白介素1家族细胞因子的处理受细胞内天然免疫反应系统的调节，该系统被称为NALP3[NACHT域，富含亮氨酸重复序列和含有吡咯域(PYD)的蛋白3]炎症体复合体。本研究采用实时定量聚合酶链式反应(PCR)技术，检测牙周炎(n=10)、慢性牙周炎(n=18)、全身性侵袭性牙周炎(n=20)及健康人(n=20)体外培养的人单核细胞系(Mono-Mac-6)中NALP3、NLRP2(NLR家族，含PYD蛋白2)、IL-1β和IL-18(I)的基因表达。临床数据表明，NALP3和NLRP2在三种类型的炎症性牙周病中的表达水平明显高于健康牙周病，而ASC的表达水平并不显著。此外，NALP3与IL-1β和IL-18在这些组织中的表达水平呈正相关。体外实验数据表明，牙龈假单胞菌通过增强NALP3，下调NLRP2和ASC的表达，解除对Mono-Mac-6细胞中NALP3炎症体复合体的调控。总之，这项研究揭示了NALP3炎症体复合体在炎症性牙周病中的作用，并通过证明细菌攻击对这一细胞因子信号通路的调节，为宿主免疫反应参与疾病的发病机制提供了一个机械性的见解。
Periodontitis is an infectious process characterized by inflammation affecting the supporting structures of the teeth. Porphyromonas gingivalis is a major oral bacterial species implicated in the pathogenesis of periodontitis. Processing of interleukin (IL)-1 family cytokines is regulated by an intracellular innate immune response system, known as the NALP3 [nacht domain-, leucine-rich repeat-, and pyrin domain (PYD)-containing protein 3] inflammasome complex. The aim of the present study was to investigate by quantitative real-time polymerase chain reaction (PCR) the mRNA expression of NALP3, its effector molecule apoptosis associated speck-like protein (ASC), its putative antagonist NLRP2 (NLR family, PYD-containing protein 2), IL-1 beta and IL-18 (i) in gingival tissues from patients with gingivitis (n = 10), chronic periodontitis (n = 18), generalized aggressive periodontitis (n = 20), as well as in healthy subjects (n = 20), (ii) in vitro in a human monocytic cell line (Mono-Mac-6), in response to P. gingivalis challenge for 6 h. The clinical data indicate that NALP3 and NLRP2, but not ASC, are expressed at significantly higher levels in the three forms of inflammatory periodontal disease compared to health. Furthermore, a positive correlation was revealed between NALP3 and IL-1 beta or IL-18 expression levels in these tissues. The in vitro data demonstrate that P. gingivalis deregulates the NALP3 inflammasome complex in Mono-Mac-6 cells by enhancing NALP3 and down-regulating NLRP2 and ASC expression. In conclusion, this study reveals a role for the NALP3 inflammasome complex in inflammatory periodontal disease, and provides a mechanistic insight to the host immune responses involved in the pathogenesis of the disease by demonstrating the modulation of this cytokine-signalling pathway by bacterial challenge.