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.
Beauséjour
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A
Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Université Laval, Québec, Canada.
Deslauriers
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N
Grenier
D
D
D000818:Animals; D002908:Chronic Disease; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010446:Peptide Fragments / Q000502:physiology*; D010518:Periodontitis / Q000209:etiology*; D011498:Protein Precursors / Q000378:metabolism*; D014208:Treponema / Q000502:physiology*
D007375:Interleukin-1; D010446:Peptide Fragments; D011498:Protein Precursors