Rapid and efficient inactivation of IL-6 gingipains, lysine- and arginine-specific proteinases from Porphyromonas gingivalis.
Deregulation of the cytokine network is an important adaptation of pathogenic bacteria to modulate and evade a host immune response. Here we describe that IL-6 is rapidly and efficiently cleaved and inactivated by the arginine- and lysine-specific proteinases from Porphyromonas gingivalis, referred to as RGP-A, RGP-B, and KGP. One of the primary cleavage sites for RGPs has been mapped between R18 and Q19 within the N-terminal region of the IL-6 polypeptide chain; however, both KGP and RGPs cleave IL-6 within the C-terminal region of the polypeptide chain. After these initial proteolytic cleavages, IL-6 is further degraded by each of the enzymes tested. Although KGP is the most potent IL-6-degrading proteinase, the initial C-terminal cleavage of IL-6 mediated by all gingipains is already sufficient to inactivate this cytokine. Our data are consistent with the observation that in periodontitis the IL-6 concentration is lowest in the gingival tissue adjacent to bacterial plaque, whereas significantly elevated concentrations of this cytokine are detected around the infected area. Degradation of IL-6 by gingipains may, therefore, represent an additional mechanism which influences the balance between pro- and anti-inflammatory reactions at distal versus proximal sites from the periodontal plaque.
Banbula
A
A
Institute of Molecular Biology, Jagiellonian University, Al. Mickiewicza 3, Krakow, 31-120, Poland.
Bugno
M
M
Kuster
A
A
Heinrich
P C
PC
Travis
J
J
Potempa
J
J
D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D001665:Binding Sites; D003545:Cysteine / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins / Q000378:metabolism*; D015850:Interleukin-6 / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D016966:Porphyromonas gingivalis / Q000201:enzymology*; D011480:Protease Inhibitors / Q000494:pharmacology
D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D015850:Interleukin-6; D011480:Protease Inhibitors; D003546:Cysteine Endopeptidases; D003545:Cysteine