title: Contradictory roles of Porphyromonas gingivalis gingipains in caspase-1 activation.
abstract: Porphyromonas gingivalis utilizes its major proteases, Arg gingipains (RgpA and RgpB) and Lys gingipain (Kgp), for dysregulation of host immune systems. The aim of this study was to investigate the roles of gingipains in caspase-1 activation and its sequelae in P. gingivalis-infected macrophages. Infection with P. gingivalis at low multiplicity of infections (MOIs), but not at high MOIs, resulted in low levels of interleukin-1β and lactate dehydrogenase without detectable active caspase-1 in the culture supernatants. The proteins released from caspase-1-activated cells were rapidly degraded by gingipains. However, P. gingivalis with gingipains induced higher intracellular caspase-1 activity in the infected cells than the gingipain-null mutant, which was associated with ATP release from the infected cells. In addition, growing the gingipain-null mutant with gingipains enhanced caspase-1 activation by the mutant. In contrast, inhibition of the protease activity of Kgp or Rgps increased the caspase-1-activating potential of wild-type P. gingivalis, indicating an inhibitory effect of the collaborative action of Kgp and Rgps. These results illuminate the contradictory roles of gingipains in the manipulation of host defence systems by P. gingivalis, as they act by both stimulating and inhibiting innate immune responses.
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-749, Korea.
authors.forename: Young-Jung
authors.initials: YJ
authors.lastname: Jung
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-749, Korea.
authors.forename: Hye-Kyoung
authors.initials: HK
authors.lastname: Jun
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-749, Korea.|Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Bong-Kyu
authors.initials: BK
authors.lastname: Choi
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D000080867:Gingipain Cysteine Endopeptidases; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000201:enzymology* / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D003546:Cysteine Endopeptidases; D020170:Caspase 1