title: Suppression of inflammatory responses of human gingival fibroblasts by gingipains from Porphyromonas gingivalis.
abstract: 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-β1 (TGF-β1 ), CXCL8, secretory leucocyte protease inhibitor (SLPI), c-Jun and indoleamine 2,3-dioxygenase (IDO). HGFs were inoculated for 6 and 24 h 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-β1 in HGFs, and the kgp mutant gave significantly higher immune response with increased CXCL8 (P < 0.001) and low levels of TGF-β1 . 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.
authors: Department of Biomedicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors: E
authors: E
authors: Palm
authors: H
authors: H
authors: Khalaf
authors: T
authors: T
authors: Bengtsson
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D000080867:Gingipain Cysteine Endopeptidases; D005881:Gingiva / Q000166:cytology / Q000276:immunology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism; D010518:Periodontitis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000201:enzymology* / Q000472:pathogenicity; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016209:Interleukin-8; D016755:Proto-Oncogene Proteins c-jun; D053481:Secretory Leukocyte Peptidase Inhibitor; D016212:Transforming Growth Factor beta; D003546:Cysteine Endopeptidases
keywords: CXCL8; gingipain; indoleamine 2,3-dioxygenase; periodontitis; secretory leucocyte protease inhibitor; transforming growth factor-β