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 pathogen ic bacteria to modulate and evade a host immune response. Here we describe that IL-6 is rapidly and efficiently cleaved and inactivated by the arginin e- 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 p olypeptide chain; however, both KGP and RGPs cleave IL-6 within the C-termi nal region of the polypeptide chain. After these initial proteolytic cleava ges, IL-6 is further degraded by each of the enzymes tested. Although KGP i s the most potent IL-6-degrading proteinase, the initial C-terminal cleavag e of IL-6 mediated by all gingipains is already sufficient to inactivate th is cytokine. Our data are consistent with the observation that in periodont itis the IL-6 concentration is lowest in the gingival tissue adjacent to ba cterial plaque, whereas significantly elevated concentrations of this cytok ine are detected around the infected area. Degradation of IL-6 by gingipain s may, therefore, represent an additional mechanism which influences the ba lance between pro- and anti-inflammatory reactions at distal versus proxima l sites from the periodontal plaque, (C) 1999 Academic Press.