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人牙龈成纤维细胞对多种体外龈下生物膜反应的转录谱分析

Transcriptional profiling of human gingival fibroblasts in response to multi-species in vitro subgingival biofilms.

作者信息

Belibasakis G N, Bao K, Bostanci N

机构信息

Oral Microbiology and Immunology, Institute of Oral Biology, Centre of Dental Medicine, University of Zürich, Zürich, Switzerland.

出版信息

Mol Oral Microbiol. 2014 Aug;29(4):174-83. doi: 10.1111/omi.12053. Epub 2014 May 13.

Abstract

Periodontitis is an infectious inflammatory disease that destroys the tooth-supporting tissues. It is initiated by complex subgingival biofilms, triggering an inflammatory response by the juxtaposed gingival tissue. The range of transcriptional events initiated in the gingiva following biofilm challenge is not fully elucidated. By employing gene microarray technology, this study aimed to characterize the overall transcriptional changes (more than two-fold regulation) of cultured human gingival fibroblasts in response to a 10-species in vitro subgingival biofilm model (BF), over a challenge period of 6 h. The relative involvement of the three 'red complex' species in these transcriptional events was evaluated by omitting these species from the biofilm composition (BF-RC). When compared with the unchallenged control, challenge with BF and BF-RC differentially regulated 386 and 428 genes, respectively, with an overlap of 52-75%. Interestingly, the expression of only three genes was significantly different between the BF and BF-RC challenged groups. There was also a strong overlap of the affected signalling pathways and gene ontology processes. These signalling pathways involved primarily the immune response, and included toll-like receptors, interleukin-1, interleukin-17 and heat-shock proteins 60 and 70. In conclusion, subgingival biofilms elicited a large number of transcriptional changes in gingival fibroblasts, while the presence of the 'red complex' in the biofilm did not yield any substantial differences. These findings show a uniform 'non-specific' transcriptional response of host cells to subgingival biofilms, and denote that redundancies may exist in the virulence properties of individual bacterial species within a polymicrobial biofilm community.

摘要

牙周炎是一种破坏牙齿支持组织的感染性炎症性疾病。它由复杂的龈下生物膜引发,通过相邻的牙龈组织触发炎症反应。生物膜刺激后牙龈中引发的转录事件范围尚未完全阐明。本研究通过基因芯片技术,旨在表征培养的人牙龈成纤维细胞在6小时的刺激期内对10种体外龈下生物膜模型(BF)的总体转录变化(超过两倍调节)。通过从生物膜组成中省略这些菌种(BF-RC)来评估三种“红色复合体”菌种在这些转录事件中的相对参与度。与未受刺激的对照相比,BF和BF-RC刺激分别差异调节了386和428个基因,重叠率为52-75%。有趣的是,BF和BF-RC刺激组之间只有三个基因的表达有显著差异。受影响的信号通路和基因本体过程也有很强的重叠。这些信号通路主要涉及免疫反应,包括Toll样受体、白细胞介素-1、白细胞介素-17以及热休克蛋白60和70。总之,龈下生物膜在牙龈成纤维细胞中引发了大量转录变化,而生物膜中“红色复合体”的存在并未产生任何实质性差异。这些发现表明宿主细胞对龈下生物膜有一致的“非特异性”转录反应,并表明在多微生物生物膜群落中单个细菌物种的毒力特性可能存在冗余。

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