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Suppression of inflammatory responses of human gingival fibroblasts by gingipains from Porphyromonas gingivalis
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Örebro University, School of Medicine, Örebro University, Sweden.
2015 (English)In: Molecular Oral Microbiology, ISSN 2041-1006, E-ISSN 2041-1014, Vol. 30, no 1, p. 74-85Article in journal (Refereed) Published
Abstract [en]

The interaction between human gingival fibroblasts (HGFs) and Porphyromonas gingivalis plays an important role in the development and progression of periodontitis. Porphyromonas gingivalis possesses several virulence factors, including cysteine proteases, the arginine-specific (Rgp) and lysine-specific (Kgp) gingipains. Studying the mechanisms that P.gingivalis, and its derived virulence, use to propagate and interact with host cells will increase the understanding of the development and progression of periodontitis. In this study, we aimed to elucidate how P.gingivalis influences the inflammatory events in HGFs regarding transforming growth factor-(1) (TGF-(1)), CXCL8, secretory leucocyte protease inhibitor (SLPI), c-Jun and indoleamine 2,3-dioxygenase (IDO). HGFs were inoculated for 6 and 24h with the wild-type strains ATCC 33277 and W50, two gingipain-mutants of W50 and heat-killed ATCC 33277. The P.gingivalis regulated CXCL8 and TGF-(1) in HGFs, and the kgp mutant gave significantly higher immune response with increased CXCL8 (P<0.001) and low levels of TGF-(1). We show that HGFs express and secrete SLPI, which was significantly suppressed by P.gingivalis (P<0.05). This suggests that by antagonizing SLPI, P.gingivalis contributes to the tissue destruction associated with periodontitis. Furthermore, we found that P.gingivalis inhibits the expression of the antimicrobial IDO, as well as upregulating c-Jun (P<0.05). In conclusion, P.gingivalis both triggers and suppresses the immune response in HGFs. Consequently, we suggest that the pathogenic effects of P.gingivalis, and especially the activity of the gingipains on the inflammatory and immune response of HGFs, are crucial in periodontitis.

Place, publisher, year, edition, pages
2015. Vol. 30, no 1, p. 74-85
Keywords [en]
CXCL8, gingipain, indoleamine 2, 3-dioxygenase, periodontitis, secretory leucocyte protease inhibitor, transforming growth factor-β
National Category
Microbiology in the medical area Medical and Health Sciences
Research subject
Microbiology; Medicine
Identifiers
URN: urn:nbn:se:oru:diva-42617DOI: 10.1111/omi.12073ISI: 000347897100007PubMedID: 25055828Scopus ID: 2-s2.0-84920913980OAI: oai:DiVA.org:oru-42617DiVA, id: diva2:788220
Funder
Swedish Research CouncilSwedish Heart Lung Foundation
Note

Funding Agencies:

Foundation of Olle Engkvist

Knowledge Foundation

Available from: 2015-02-13 Created: 2015-02-13 Last updated: 2018-01-11Bibliographically approved
In thesis
1. Inflammatory responses of gingival fibroblasts in the interaction with the periodontal pathogen Porphyromonas gingivalis
Open this publication in new window or tab >>Inflammatory responses of gingival fibroblasts in the interaction with the periodontal pathogen Porphyromonas gingivalis
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro university, 2015. p. 70
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 113
Keywords
Porphyromonas gingivalis, fibroblasts, CXCL8, TGF-β1, IL-6, SLPI, IDO, c-JUN, PKC, p38, periodontitis
National Category
Medical and Health Sciences Biomedical Laboratory Science/Technology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-38660 (URN)978-91-7529-056-0 (ISBN)
Public defence
2015-02-06, Universitetssjukhuset, Bomanssonsalen, Södra Grev Rosengatan, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2014-11-17 Created: 2014-11-17 Last updated: 2017-10-17Bibliographically approved

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Palm, EleonorKhalaf, HazemBengtsson, Torbjörn

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School of Health and Medical Sciences, Örebro University, SwedenSchool of Medicine, Örebro University, Sweden
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Molecular Oral Microbiology
Microbiology in the medical areaMedical and Health Sciences

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