Dual regulation of interleukin-8 production in human oral epithelial cells upon stimulation with gingipains from Porphyromonas gingivalis.
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.
Uehara
Akiko
A
Department of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Naito
Mariko
M
Division of Microbiology and Oral Infection, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Imamura
Takahisa
T
Division of Molecular Pathology, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Potempa
Jan
J
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA.|Department of Microbiology, Faculty of Biotechnology, Jagiellonian University, Kraków, Poland.
Travis
James
J
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA.
Nakayama
Koji
K
Division of Microbiology and Oral Infection, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Takada
Haruhiko
H
Department of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
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
D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D016209:Interleukin-8; D003546:Cysteine Endopeptidases