title: Identification and Characterization of MicroRNA Differentially Expressed in Macrophages Exposed to Porphyromonas gingivalis Infection.
abstract: MicroRNAs (miRNAs) are short, noncoding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Bacterial infection modulates miRNA expression to subvert any innate immune response. In this study we analyzed, using microarray analysis, the bacterial modulation of miRNAs in bone marrow-derived macrophages (BMMs) in which activity was induced by infection withPorphyromonas gingivalisThe expression of several miRNAs was modulated 3 h postinfection (at a multiplicity of infection of 25). A bioinformatic analysis was performed to further identify pathways related to the innate immune host response under the influence of selected miRNAs. To assess the effects of the miRNAs identified on cytokine secretion (tumor necrosis factor alpha [TNF-α] and interleukin-10 [IL-10]), BMMs were transfected with selected miRNA mimics and inhibitors. Transfection with mmu-miR-155 and mmu-miR-2137 did not modify TNF-α secretion, while their inhibitors increased it. Inhibitors of mmu-miR-2137 and mmu-miR-7674 increased the secretion of the anti-inflammatory factor IL-10. InP. gingivalis-infected BMMs, mmu-miR-155-5p significantly decreased TNF-α secretion while inhibitor of mmu-miR-2137 increased IL-10 secretion.In vivo, in a mouse model ofP. gingivalis-induced calvarial bone resorption, injection of mmu-miR-155-5p or anti-mmu-miR-2137 reduced the size of the lesion significantly. Furthermore, anti-mmu-miR-2137 significantly reduced inflammatory cell infiltration, osteoclast activity, and bone loss. Bioinformatic analysis demonstrated that pathways related to cytokine- and chemokine-related pathways but also osteoclast differentiation may be involved in the effects observed. This study contributes further to our understanding ofP. gingivalis-induced modulation of miRNAs and their physiological effects. It highlights the potential therapeutic merits of targeting mmu-miR-155-5p and mmu-miR-2137 to control inflammation induced byP. gingivalisinfection.
authors.affiliation: Université de Strasbourg, Faculté de Chirurgie-Dentaire, Department of Periodontology, Strasbourg, France.|INSERM 1109, Osteoarticular & Dental Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.|Department of Molecular and Cell Biology, Boston University School of Dental Medicine, Boston, Massachusetts, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Huck
authors.affiliation: Department of Molecular and Cell Biology, Boston University School of Dental Medicine, Boston, Massachusetts, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Al-Hashemi
authors.affiliation: Complex Systems and Translational Bioinformatics, ICube, UMR 7357, CNRS, Université de Strasbourg, Fédération de Médecine Translationnelle, Strasbourg, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Poidevin
authors.affiliation: Complex Systems and Translational Bioinformatics, ICube, UMR 7357, CNRS, Université de Strasbourg, Fédération de Médecine Translationnelle, Strasbourg, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Poch
authors.affiliation: Université de Strasbourg, Faculté de Chirurgie-Dentaire, Department of Periodontology, Strasbourg, France.|INSERM 1109, Osteoarticular & Dental Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Davideau
authors.affiliation: Université de Strasbourg, Faculté de Chirurgie-Dentaire, Department of Periodontology, Strasbourg, France.|INSERM 1109, Osteoarticular & Dental Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Tenenbaum
authors.affiliation: Department of Pharmacology, NYMC, Touro College and University System, Valhalla, New York, USA salomon_amar@nymc.edu.
authors.forename: Salomon
authors.initials: S
authors.lastname: Amar
mesh_terms: D000818:Animals; D016866:Bacteroidaceae Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology*; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D016966:Porphyromonas gingivalis / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Porphyromonas gingivalis; inflammation; innate immunity; macrophages; miRNA