Abstract |
Cysteine proteinases from Porphyromonas gingivalis, or gingipains, are considered to be key virulence factors of the bacterium in relation to periodontal diseases. Incubation of human oral epithelial cells with lysine-specific gingipain (Kgp) and high-molecular-mass arginine-specific gingipain (HRgpA) resulted in a decrease in the production of interleukin (IL)-8, but not in the production of other pro-inflammatory cytokines. In contrast, arginine-specific gingipain 2 (RgpB) increased IL-8 production. RNA interference assays demonstrated that Kgp- and HRgpA-mediated downregulation and RgpB-mediated upregulation occurred through protease-activated receptor (PAR)-1 and PAR-2 signalling. Although the RgpB-mediated upregulation of IL-8 production occurred through nuclear factor-kappa B ( NF-kappaB), the Kgp- and HRgpA-mediated downregulation was not negated in NF-kappaB-silenced cells. Both the haemagglutinin and the enzymic domains are required for Kgp and HRgpA to downregulate the production of IL-8 in human oral epithelial cells, and the two domains are thought to co-exist. These results suggest that gingipains preferentially suppress IL-8, resulting in attenuation of the cellular recognition of bacteria, and as a consequence, sustain chronic inflammation.
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Authors | Akiko Uehara, Mariko Naito, Takahisa Imamura, Jan Potempa, James Travis, Koji Nakayama, Haruhiko Takada |
Journal | Journal of medical microbiology
(J Med Microbiol)
Vol. 57
Issue Pt 4
Pg. 500-507
(Apr 2008)
ISSN: 0022-2615 [Print] England |
PMID | 18349372
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adhesins, Bacterial
- Gingipain Cysteine Endopeptidases
- Interleukin-8
- Cysteine Endopeptidases
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Topics |
- Adhesins, Bacterial
(metabolism, pharmacology, physiology)
- Cell Line, Tumor
- Cysteine Endopeptidases
(metabolism, pharmacology, physiology)
- Down-Regulation
- Epithelial Cells
(immunology, microbiology)
- Gene Expression Regulation
- Gingipain Cysteine Endopeptidases
- Humans
- Interleukin-8
(biosynthesis)
- Mouth Mucosa
(cytology, immunology)
- Porphyromonas gingivalis
(enzymology, immunology, metabolism)
- Up-Regulation
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