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The role of toll-like and protease-activated receptors in the expression of cytokines by gingival fibroblasts stimulated with the periodontal pathogen Porphyromonas gingivalis
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Biomedicine, Örebro University Hospital, Örebro, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Biomedicine, Örebro University Hospital, Örebro, Sweden.
Örebro University, School of Medicine, Örebro University, Sweden. Department of Biomedicine, Örebro University Hospital, Örebro, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Biomedicine, Örebro University Hospital, Örebro, Sweden.
2015 (English)In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 76, no 2, p. 424-432Article in journal (Refereed) Published
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Text
Abstract [en]

Porphyromonas gingivalis is a periodontitis-associated pathogen and interactions between the bacterium and gingival fibroblasts play an important role in development and progression of periodontitis, an inflammatory disease leading to degeneration of tooth-supporting structures. Gingival fibroblasts, which expresses protease activated receptors (PARs) as well as toll-like receptors (TLRs), produces inflammatory mediators upon bacterial challenges. In this study, we elucidated the importance of PAR1, PAR2, TLR2 and TLR4 for the expression and secretion of CXCL8, interleukin-6 (IL-6), transforming growth factor-beta 1 (TGF-beta 1) and secretory leukocyte inhibitor (SLPI). Human gingival fibroblasts were transfected with small-interfering RNA against the target genes, and then stimulated with P. gingivalis wild-type W50 and W50-derived double rgp mutant E8 and kgp mutant K1A. TLR2-silencing reduced P. gingivalis-induced CXCL8 and IL-6. IL-6 was also reduced after PAR1-silencing. No effects were observed for TGF-beta 1. SLPI was suppressed by P. gingivalis and silencing of PAR1 as well as TLR2, gave additional suppression at the mRNA level. TLR4 was not involved in the regulation of the investigated mediators. CXCL8 and IL-6 are important for progression and development of periodontitis, leading to a chronic inflammation that may contribute to the tissue destruction that follows an exacerbated host response. Therefore, regulating the expression of TLR2 and subsequent release of CXCL8 and IL-6 in periodontitis could attenuate the tissue destruction seen in periodontitis.

Place, publisher, year, edition, pages
Academic Press, 2015. Vol. 76, no 2, p. 424-432
Keywords [en]
Fibroblasts, Porphyromonas gingivalis, CXCL8, Interleukin-6, Secretory leukocyte protease inhibitor
National Category
Microbiology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Immunology in the medical area
Research subject
Biomedicine; Immunology
Identifiers
URN: urn:nbn:se:oru:diva-47006DOI: 10.1016/j.cyto.2015.08.263ISI: 000364244400041PubMedID: 26318255Scopus ID: 2-s2.0-84943819518OAI: oai:DiVA.org:oru-47006DiVA, id: diva2:878719
Funder
Swedish Research CouncilSwedish Heart Lung FoundationKnowledge Foundation
Note

Funding Agencies:

Mats Kleberg Foundation

Foundation of Olle Engkvist

Available from: 2015-12-09 Created: 2015-12-09 Last updated: 2018-07-02Bibliographically approved

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Palm, EleonorDemirel, IsakBengtsson, TorbjörnKhalaf, Hazem

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Palm, EleonorDemirel, IsakBengtsson, TorbjörnKhalaf, Hazem
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School of Health and Medical Sciences, Örebro University, SwedenSchool of Medicine, Örebro University, Sweden
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Cytokine
Microbiology in the medical areaMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)Immunology in the medical area

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