Inhibition of the activities of matrix metalloproteinases 2, 8, and 9 by chlorhexidine.
Matrix metalloproteinases (MMPs) are a host cell-derived proteolytic enzyme family which plays a major role in tissue-destructive inflammatory diseases such as periodontitis. The aim of the present study was to evaluate the inhibitory effect of chlorhexidine (CHX) on MMP-2 (gelatinase A), MMP-9 (gelatinase B), and MMP-8 (collagenase 2) activity. Heat-denatured type I collagen (gelatin) was incubated with pure human MMP-2 or -9 activated with p-aminophenylmercuric acetate (APMA), and the proteolytic degradation of gelatin was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Coomassie blue staining. The effect of CHX on MMP-8 activity was also studied with a cellular model addressing the ability of phorbol myristate acetate (PMA)-triggered human peripheral blood neutrophils (polymorphonuclear leukocytes [PMNs]) to degrade native type I collagen. CHX inhibited the activities of both gelatinases (A and B), but MMP-2 appeared to be more sensitive than MMP-9. Adding calcium chloride to the assay mixtures almost completely prevented the inhibition of MMP-9 activity by CHX, while the inhibition of MMP-2 activity could be reversed only when CHX was used at a low concentration. This observation suggests that CHX may act via a cation-chelating mechanism. CHX dose-dependently inhibited collagenolytic activity of MMP-8 released by PMA-triggered PMNs. MMP-8 without APMA activation was inhibited clearly more efficiently than APMA-activated MMP-8. Our study suggests that the direct inhibition of the MMPs' activities by CHX may represent a new valuable effect of this antimicrobial agent and explains, at least in part, the beneficial effects of CHX in the treatment of periodontitis.
Gendron
R
R
Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Université Laval, Québec, Canada.
Grenier
D
D
Sorsa
T
T
Mayrand
D
D
D002710:Chlorhexidine / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D018093:Gelatinases / Q000037:antagonists & inhibitors; D006801:Humans; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D011480:Protease Inhibitors / Q000494:pharmacology; D012394:Rosaniline Dyes; D013194:Staining and Labeling
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D012394:Rosaniline Dyes; C048139:Coomassie blue; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D002710:Chlorhexidine