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Porphyromonas gingivalis downregulates the immune response of fibroblasts
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.
2013 (English)In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 13, p. 155-Article in journal (Refereed) Published
Abstract [en]

Background: Porphyromonas gingivalis is a key pathogen in periodontitis, an inflammatory disease leading to destruction of bone and tooth-supporting tissue. P. gingivalis possesses a number of pathogenic properties to enhance growth and survival, including proteolytic gingipains. Accumulating data shows that gingipains are involved in the regulation of host inflammatory responses. The aim of this study was to determine if P. gingivalis infection modulates the inflammatory response of fibroblasts, including the release of chemokines and cytokines. Human gingival fibroblasts or primary dermal fibroblasts were pre-stimulated with tumor-necrosis factor-alpha (TNF-alpha) and cocultured with P. gingivalis. Gingipain inhibitors were used to explore the effect of gingipains. CXCL8 levels were determined with ELISA and the relative levels of various inflammatory mediators were determined by a cytokine assay.

Results: TNF-alpha-triggered CXCL8 levels were completely abolished by viable P. gingivalis, whereas heat-killed P. gingivalis did not suppress CXCL8. Accumulation of CXCL8 was partially restored by an arginine-gingipain inhibitor. Furthermore, fibroblasts produced several inflammatory mediators, notably chemokines, all of which were suppressed by viable P. gingivalis.

Conclusion: These findings provide evidence that fibroblast-derived inflammatory signals are modulated by heat-instable gingipains, whereby the bacteria can escape killing by the host immune system and promote its own growth and establishment. In addition, we show that fibroblasts are important mediators of inflammation in response to infection and thereby play a crucial role in determining the nature and magnitude of the invasion of immune cells.

Place, publisher, year, edition, pages
2013. Vol. 13, p. 155-
Keywords [en]
Porphyromonas gingivalis, Fibroblasts, Chemokines, Cytokines
National Category
Microbiology in the medical area
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-30310DOI: 10.1186/1471-2180-13-155ISI: 000322041700001Scopus ID: 2-s2.0-84880027349OAI: oai:DiVA.org:oru-30310DiVA, id: diva2:642752
Funder
Swedish Research CouncilSwedish Heart Lung Foundation
Note

Funding Agency: Foundation of Olle Engkvist; Mats Kleberg Foundation

Available from: 2013-08-23 Created: 2013-08-23 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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Microbiology in the medical area

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