title: Porphyromonas gingivalis downregulates the immune response of fibroblasts.
abstract: 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-α (TNF- α) 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-α-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden. eleonor.palm@oru.se
authors.forename: Eleonor
authors.initials: E
authors.lastname: Palm
authors.forename: Hazem
authors.initials: H
authors.lastname: Khalaf
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Bengtsson
mesh_terms: D002478:Cells, Cultured; D018920:Coculture Techniques; D005347:Fibroblasts / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D057131:Immune Evasion; D016209:Interleukin-8 / Q000276:immunology; D050296:Microbial Viability; D016966:Porphyromonas gingivalis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha