title: The role of toll-like and protease-activated receptors and associated intracellular signaling in Porphyromonas gingivalis-infected gingival fibroblasts.
abstract: Porphyromonas gingivalis, which is considered a keystone agent in periodontitis, has evolved elaborate mechanisms to grow and survive in a hostile milieu. The gingival fibroblast is the major cell type in the gingiva and is considered to be important in the periodontitis-associated inflammation. As a part of the innate immune response, they produce cytokines such as CXCL8 and interleukin (IL)-6 which are believed to contribute to the destruction of the tooth-supporting tissues. This study investigates how the expression of protease-activated receptors (PAR1, PAR2) and toll-like receptors (TLR2, TLR4) changes with P. gingivalis exposure and how silencing of one receptor affects the expression of the other receptors. The importance of protein kinase C (PKC) and p38 in the regulation of CXCL8 and IL-6 was also examined. Receptors were knockdown with small-interfering RNA. PKC or p38 was blocked prior to stimulation with P. gingivalis. Fibroblasts were able to compensate for PAR1 knockdown with increased expression of PAR2. PKC and p38 were involved in the regulation of P. gingivalis-induced CXCL8 and IL-6. Our results indicate that PAR1 and PAR2 could be implicated in periodontitis and that PKC and P38 play a role in the inflammatory response in P. gingivalis-infected gingival fibroblasts.
authors.affiliation: School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Eleonor
authors.initials: E
authors.lastname: Palm
authors.affiliation: School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Isak
authors.initials: I
authors.lastname: Demirel
authors.affiliation: School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Bengtsson
authors.affiliation: School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Hazem
authors.initials: H
authors.lastname: Khalaf
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology* / Q000382:microbiology*; D020869:Gene Expression Profiling; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000276:immunology*; D011493:Protein Kinase C / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D044462:Receptors, Proteinase-Activated / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D044462:Receptors, Proteinase-Activated; D051193:Toll-Like Receptors; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases
keywords: 
  Porphyromonas gingivalis
  ; cell signaling; gingival fibroblasts; protease-activated receptors; toll-like receptors