title: Dual regulation of interleukin-8 production in human oral epithelial cells upon stimulation with gingipains from Porphyromonas gingivalis.
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.
authors: Department of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors: Akiko
authors: A
authors: Uehara
authors: Division of Microbiology and Oral Infection, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Mariko
authors: M
authors: Naito
authors: Division of Molecular Pathology, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Takahisa
authors: T
authors: Imamura
authors: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA.|Department of Microbiology, Faculty of Biotechnology, Jagiellonian University, Kraków, Poland.
authors: Jan
authors: J
authors: Potempa
authors: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA.
authors: James
authors: J
authors: Travis
authors: Division of Microbiology and Oral Infection, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Koji
authors: K
authors: Nakayama
authors: Department of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors: Haruhiko
authors: H
authors: Takada
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D005786:Gene Expression Regulation; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D009061:Mouth Mucosa / Q000166:cytology / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D016209:Interleukin-8; D003546:Cysteine Endopeptidases