Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Mol Oral Microbiol. 2012 Feb;27(1):23-33. doi: 10.1111/j.2041-1014.2011.00629.x. Epub 2011 Nov 15.
Periodontal diseases result from the interaction of bacterial pathogens with the host's gingival tissue. Gingival epithelial cells are constantly challenged by microbial cells and respond by altering their transcription profiles, inducing the production of inflammatory mediators. Different transcription profiles are induced by oral bacteria and little is known about how the gingival epithelium responds after interaction with the periodontopathogenic organism Aggregatibacter actinomycetemcomitans. In the present study, we examined the transcription of genes involved in signaling transduction pathways in gingival epithelial cells exposed to viable A. actinomycetemcomitans. Immortalized gingival epithelial cells (OBA-9) were infected with A. actinomycetemcomitans JP2 for 24 h and the transcription profile of genes encoding human signal transduction pathways was determined. Functional analysis of inflammatory mediators positively transcribed was performed by ELISA in culture supernatant and in gingival tissues. Fifteen of 84 genes on the array were over-expressed (P < 0.01) after 24 h of infection with viable A. actinomycetemcomitans. Over-expressed genes included those implicated in tissue remodeling and bone resorption, such as CSF2, genes encoding components of the LDL pathway, nuclear factor-κB-dependent genes and other cytokines. The ELISA data confirmed that granulocyte-macrophage colony-stimulating factor/colony-stimulating factor 2, tumor necrosis factor-α and intercellular adhesion molecule-1 were highly expressed by infected gingival cells when compared with control non-infected cells, and presented higher concentrations in tissues from patients with aggressive and chronic periodontitis than in tissues from healthy controls. The induction in epithelial cells of factors such as the pro-inflammatory cytokine CSF2, which is involved in osteoclastogenesis, may help to explain the outcomes of A. actinomycetemcomitans infection.
牙周病是由细菌病原体与宿主牙龈组织相互作用引起的。牙龈上皮细胞不断受到微生物细胞的挑战，并通过改变其转录谱来响应，从而诱导炎症介质的产生。口腔细菌会诱导不同的转录谱，而对于牙龈上皮在与牙周致病菌聚集放线杆菌相互作用后如何反应，人们知之甚少。在本研究中，我们研究了暴露于活的 A. actinomycetemcomitans 的牙龈上皮细胞中参与信号转导途径的基因的转录。用 A. actinomycetemcomitans JP2 感染永生化的牙龈上皮细胞（OBA-9）24 小时，并确定编码人类信号转导途径的基因的转录谱。通过 ELISA 在培养上清液和牙龈组织中对转录呈阳性的炎症介质进行功能分析。在感染活的 A. actinomycetemcomitans 24 小时后，84 个基因中有 15 个（P < 0.01）过表达。过表达的基因包括与组织重塑和骨吸收有关的基因，如 CSF2、编码 LDL 途径成分的基因、核因子-κB 依赖性基因和其他细胞因子。ELISA 数据证实，与对照未感染细胞相比，感染牙龈细胞中粒细胞-巨噬细胞集落刺激因子/集落刺激因子 2、肿瘤坏死因子-α和细胞间黏附分子-1 的表达水平较高，并且在侵袭性和慢性牙周炎患者的组织中表达水平高于健康对照组。上皮细胞中促炎细胞因子 CSF2 的诱导，CSF2 参与破骨细胞形成，这可能有助于解释 A. actinomycetemcomitans 感染的结果。
