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Suppression of inflammatory responses of human gingival fibroblasts by gingipains from Porphyromonas gingivalis
Örebro universitet, Institutionen för hälsovetenskap och medicin.
Örebro universitet, Institutionen för hälsovetenskap och medicin.
Örebro universitet, Institutionen för läkarutbildning.
2015 (engelsk)Inngår i: Molecular Oral Microbiology, ISSN 2041-1006, E-ISSN 2041-1014, Vol. 30, nr 1, s. 74-85Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
2015. Vol. 30, nr 1, s. 74-85
Emneord [en]
CXCL8, gingipain, indoleamine 2, 3-dioxygenase, periodontitis, secretory leucocyte protease inhibitor, transforming growth factor-β
HSV kategori
Forskningsprogram
Mikrobiologi; Medicin
Identifikatorer
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
Forskningsfinansiär
Swedish Research CouncilSwedish Heart Lung Foundation
Merknad

Funding Agencies:

Foundation of Olle Engkvist

Knowledge Foundation

Tilgjengelig fra: 2015-02-13 Laget: 2015-02-13 Sist oppdatert: 2018-01-11bibliografisk kontrollert
Inngår i avhandling
1. Inflammatory responses of gingival fibroblasts in the interaction with the periodontal pathogen Porphyromonas gingivalis
Åpne denne publikasjonen i ny fane eller vindu >>Inflammatory responses of gingival fibroblasts in the interaction with the periodontal pathogen Porphyromonas gingivalis
2015 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
sted, utgiver, år, opplag, sider
Örebro: Örebro university, 2015. s. 70
Serie
Örebro Studies in Medicine, ISSN 1652-4063 ; 113
Emneord
Porphyromonas gingivalis, fibroblasts, CXCL8, TGF-β1, IL-6, SLPI, IDO, c-JUN, PKC, p38, periodontitis
HSV kategori
Forskningsprogram
Biomedicin
Identifikatorer
urn:nbn:se:oru:diva-38660 (URN)978-91-7529-056-0 (ISBN)
Disputas
2015-02-06, Universitetssjukhuset, Bomanssonsalen, Södra Grev Rosengatan, Örebro, 09:00 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2014-11-17 Laget: 2014-11-17 Sist oppdatert: 2017-10-17bibliografisk kontrollert

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