1887

Abstract

Cysteine proteinases from , 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-B), the Kgp- and HRgpA-mediated downregulation was not negated in NF-B-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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2008-04-01
2020-04-08
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