title: Secreted gingipains from Porphyromonas gingivalis colonies exert potent immunomodulatory effects on human gingival fibroblasts.
abstract: Periodontal pathogens, including Porphyromonas gingivalis, can form biofilms in dental pockets and cause inflammation, which is one of the underlying mechanisms involved in the development of periodontal disease, ultimately leading to tooth loss. Although P. gingivalis is protected in the biofilm, it can still cause damage and modulate inflammatory responses from the host, through secretion of microvesicles containing proteinases. The aim of this study was to evaluate the role of cysteine proteinases in P. gingivalis colony growth and development, and subsequent immunomodulatory effects on human gingival fibroblast. By comparing the wild type W50 with its gingipain deficient strains we show that cysteine proteinases are required by P. gingivalis to form morphologically normal colonies. The lysine-specific proteinase (Kgp), but not arginine-specific proteinases (Rgps), was associated with immunomodulation. P. gingivalis with Kgp affected the viability of gingival fibroblasts and modulated host inflammatory responses, including induction of TGF-β1 and suppression of CXCL8 and IL-6 accumulation. These results suggest that secreted products from P. gingivalis, including proteinases, are able to cause damage and significantly modulate the levels of inflammatory mediators, independent of a physical host-bacterial interaction. This study provides new insight of the pathogenesis of P. gingivalis and suggests gingipains as targets for diagnosis and treatment of periodontitis.
authors: Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors: Torbjörn
authors: T
authors: Bengtsson
authors: The PRO-CARE Group, School of Health and Society, Kristianstad University, Kristianstad, Sweden.
authors: Atika
authors: A
authors: Khalaf
authors: Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden. Electronic address: hazem.khalaf@oru.se.
authors: Hazem
authors: H
authors: Khalaf
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000276:immunology* / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology*; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism* / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000201:enzymology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D007155:Immunologic Factors; D015850:Interleukin-6; D016209:Interleukin-8; D053773:Transforming Growth Factor beta1; D003546:Cysteine Endopeptidases
keywords: Cytokine; Fibroblast; Gingipain; Porphyromonas gingivalis; Proteinase