title: Genome-wide transcriptome induced by Porphyromonas gingivalis LPS supports the notion of host-derived periodontal destruction and its association with systemic diseases.
abstract: 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.
authors.affiliation: Center of Dento-Maxillo-Facial Medicine, University Hospital of Bonn, Bonn, Germany lgoelz@uni-bonn.de.
authors.forename: Lina
authors.initials: L
authors.lastname: Gölz
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Benedikt C
authors.initials: BC
authors.lastname: Buerfent
authors.affiliation: Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hofmann
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Hübner
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University Hospital of Bonn, Bonn, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Rühl
authors.affiliation: Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Fricker
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Schmidt
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University Hospital of Bonn, Bonn, Germany.
authors.forename: Oldenburg
authors.initials: O
authors.lastname: Johannes
authors.affiliation: Center of Dento-Maxillo-Facial Medicine, University Hospital of Bonn, Bonn, Germany.
authors.forename: Søren
authors.initials: S
authors.lastname: Jepsen
authors.affiliation: Center of Dento-Maxillo-Facial Medicine, University Hospital of Bonn, Bonn, Germany.
authors.forename: James
authors.initials: J
authors.lastname: Deschner
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.affiliation: Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
authors.affiliation: Center of Dento-Maxillo-Facial Medicine, University Hospital of Bonn, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jäger
mesh_terms: D000328:Adult; D001168:Arthritis / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics; D016866:Bacteroidaceae Infections / Q000235:genetics / Q000276:immunology*; D063646:Carcinogenesis / Q000235:genetics; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D055113:Chronic Periodontitis / Q000276:immunology*; D016678:Genome; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000276:immunology*; D059467:Transcriptome; D055815:Young Adult
chemical_list: C105504:CCL23 protein, human; D019742:Chemokines, CC; D008070:Lipopolysaccharides
keywords: Porphyromonas gingivalis; human monocytes; innate immunity; periodontitis; transcriptome