Abstract | BACKGROUND/PURPOSE:
Lysine-specific gingipain (Kgp) is a virulence factor secreted from Porphyromonas gingivalis (P. gingivalis), a major etiological bacterium of periodontal disease. Keratin intermediate filaments maintain the structural integrity of gingival epithelial cells, but are targeted by Kgp to produce a novel cytokeratin 6 fragment (K6F). We investigated the release of K6F and its induction of cytokine secretion. METHODS: K6F present in the gingival crevicular fluid of periodontal disease patients and in gingipain-treated rat gingival epithelial cell culture supernatants was measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometer-based rapid quantitative peptide analysis using BLOTCHIP. K6F in gingival tissues was immunostained, and cytokeratin 6 protein was analyzed by immunofluorescence staining and flow cytometry. Activation of MAPK in gingival epithelial cells was evaluated by immunoblotting. ELISA was used to measure K6F and the cytokines release induced by K6F. Human gingival fibroblast migration was assessed using a Matrigel invasion chamber assay. RESULTS: CONCLUSION: Kgp degrades gingival epithelial cell cytokeratin 6 to K6F that, on release, induces invasion and cytokine secretion by human gingival fibroblasts. Thus, Kgp may contribute to the development of periodontal disease.
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Authors | Salunya Tancharoen, Takashi Matsuyama, Ko-Ichi Kawahara, Kenji Tanaka, Lyang-Ja Lee, Miho Machigashira, Kazuyuki Noguchi, Takashi Ito, Takahisa Imamura, Jan Potempa, Kiyoshi Kikuchi, Ikuro Maruyama |
Journal | PloS one
(PLoS One)
Vol. 10
Issue 2
Pg. e0117775
( 2015)
ISSN: 1932-6203 [Electronic] United States |
PMID | 25688865
(Publication Type: Journal Article)
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Chemical References |
- Adhesins, Bacterial
- Cytokines
- Gingipain Cysteine Endopeptidases
- Keratin-6
- Cysteine Endopeptidases
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Topics |
- Adhesins, Bacterial
(pharmacology)
- Animals
- Cells, Cultured
- Cysteine Endopeptidases
(pharmacology)
- Cytokines
(metabolism)
- Epithelial Cells
(drug effects, metabolism, pathology)
- Gingipain Cysteine Endopeptidases
- Gingiva
(drug effects, metabolism, pathology)
- Gingival Crevicular Fluid
(drug effects, metabolism)
- Humans
- Inflammation
(metabolism, pathology)
- Keratin-6
(metabolism)
- Periodontitis
(metabolism, pathology)
- Porphyromonas gingivalis
- Rats
- Signal Transduction
(drug effects)
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