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Activation of the interleukin-1beta precursor by Treponema denticola: a potential role in chronic inflammatory periodontal diseases

There are several indications suggesting that interleukin-1beta (IL-1beta) may play an important role in inflammatory periodontal diseases. We hypothesized that periodontal sites would represent a unique combination of both cellular sources of IL-1beta precursor (pro-IL-1beta) and microbial proteases and proposed that Treponema denticola, a suspected periodontal pathogen, would play a critical role in the inflammatory nature of adult chronic periodontitis by activating pro-IL-1beta. The aim of this study was thus to demonstrate the proteolytic cleavage and activation of the inactive precursor pro-IL-1beta by T. denticola. After incubation of bacterial cells with recombinant pro-IL-1beta, proteolytic cleavage was monitored by Western immunoblotting, and the biological activity of the digestion products was tested in a bioassay. We report here that T. denticola can cleave pro-IL-1beta to yield two fragments with molecular masses of 18 and 19 kDa. Cleavage products showed a dose-dependent biological activity in the thymocyte proliferation bioassay, and this activity was inhibited by anti-IL-1beta neutralizing antibodies. These results suggest that T. denticola may have a proinflammatory role in periodontal diseases.