Genome-wide transcriptome induced by Porphyromonas gingivalis LPS supports the notion of host-derived periodontal destruction and its association with systemic diseases

摘要

Chronic periodontitis (CP) is a prevalent pathogen-associated inflammatory disorder characterized by the destruction of tooth-supporting tissues, and linked to several systemic diseases. Both the periodontopathogen Porphyromonas gingivalis (Pg), and the genetically determined host immune response, are hypothesized to play a crucial role in this association. To identify new target genes for CP and its associated systemic diseases, we investigated the transcriptome induced by Pg in human monocytes using a genome-wide approach. Monocytes were isolated from healthy male volunteers of European origin and challenged with the Pg virulence factor LPS. Array-based gene expression analysis comprising >47,000 transcripts was performed followed by pathway analyses. Transcriptional data were validated by protein and cell surface markers. LPS Pg challenge led to the significant induction of 902 transcripts. Besides known periodontitis-associated targets, several new candidates were identified (CCL23, INDO, GBP 1/4, CFB, ISG20, MIR155HG, DHRS9). Moreover, various transcripts correspond to the host immune response, and have been linked to cancer, atherosclerosis and arthritis, thus highlighting the systemic impact of CP. Protein data of immunological markers validated our results. The present findings expand understanding of Pg elicited immune responses, and indicate new target genes and pathways of relevance to diagnostic and therapeutic strategies.