title: Porphyromonas gingivalis-impaired innate immune response via NLRP3 proteolysis in endothelial cells.
abstract: Porphyromonas gingivalis (Pg) is involved in the link between periodontal diseases and atherosclerosis worsening. In periodontal cells, Pg modifies IL-1β expression via the NLRP3 inflammasome pathway activation. Our aim was to investigate NLRP3 inflammasome activation in endothelial cells (ECs) after Pg infection and Pg-LPS stimulation. In both situations, RT-PCR experiments demonstrated an increase of the NLRP3 mRNA level that can be potentiated by pre-treatment of ECs with 5 mM ATP. However, Western blotting analysis revealed that Pg infection induced a proteolysis of NLRP3 protein and a major decrease of the native protein. After ATP pre-treatment and/or Pg-LPS stimulation, this proteolysis was not observed, while NLRP3 protein levels were increased. Proteolysis of the NLRP3 protein was not observed with heat-killed Pg and inhibition of ECs protein synthesis with cycloheximide did not abolish the NLRP3 protein degradation induced by Pg infection in ATP pre-treated cells. Additionally, significant increases of secreted IL-1β were measured after ATP pre-treatment and/or Pg-LPS stimulation, but not after Pg infection. These data showed that Pg and Pg-LPS differentially controlled the NLRP3 inflammasome pathway in ECs, and suggested a novel potential mechanism developed by Pg to reduce IL-1β secretion and to escape host immune response.
authors.affiliation: INSERM UMR 1109, Institut National de la Santé et de la Recherche Médicale, "Osteoarticular and Dental Regenerative Nanomedicine" Team, Strasbourg, France Department of Periodontology, Dental Faculty, University of Strasbourg, Strasbourg, France huck.olivier@gmail.com.
authors.forename: Olivier
authors.initials: O
authors.lastname: Huck
authors.affiliation: INSERM UMR 1109, Institut National de la Santé et de la Recherche Médicale, "Osteoarticular and Dental Regenerative Nanomedicine" Team, Strasbourg, France Dental Faculty, University of Strasbourg, Strasbourg, France.
authors.forename: René
authors.initials: R
authors.lastname: Elkaim
authors.affiliation: INSERM UMR 1109, Institut National de la Santé et de la Recherche Médicale, "Osteoarticular and Dental Regenerative Nanomedicine" Team, Strasbourg, France Department of Periodontology, Dental Faculty, University of Strasbourg, Strasbourg, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Davideau
authors.affiliation: INSERM UMR 1109, Institut National de la Santé et de la Recherche Médicale, "Osteoarticular and Dental Regenerative Nanomedicine" Team, Strasbourg, France Department of Periodontology, Dental Faculty, University of Strasbourg, Strasbourg, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Tenenbaum
mesh_terms: D016866:Bacteroidaceae Infections / Q000276:immunology* / Q000382:microbiology; D002352:Carrier Proteins / Q000276:immunology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D042783:Endothelial Cells / Q000276:immunology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D058847:Inflammasomes; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D016966:Porphyromonas gingivalis / Q000276:immunology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003513:Cycloheximide
keywords: Inflammasome; NLRP3; Porphyromonas gingivalis; atherosclerosis; endothelial; inflammation