Tetracyclines have recently been shown to inhibit the activity of mammalian
matrix metalloproteinases, i.e. type I
collagenase (MMP-1) and type IV
collagenase/
gelatinase (MMP-2). The specificity of this effect, however, has not been examined in detail. In the present study,
doxycycline (a clinically widely used commercial
tetracycline) and
4-de-dimethylaminotetracycline (CMT-1, a chemically modified non-antimicrobial
tetracycline) were tested, at a wide range of concentrations, for their ability to inhibit human neutrophil and fibroblast interstitial
collagenases, which are distinct gene products, as well as
collagenase in human gingival crevicular fluid (an inflammatory exudate in periodontal lesions) obtained from adult, juvenile and diabetic
adult periodontitis patients. The concentrations of these two
tetracyclines, required to inhibit 50% of the
collagenase activity (IC50), were found to be 15-30 microM for purified human
neutrophil collagenase as well as
collagenase in gingival crevicular fluid of
adult periodontitis patients and diabetic
adult periodontitis patients, thus approximating in vivo therapeutic
tetracycline levels. In contrast, the
fibroblast collagenase and
collagenase in gingival crevicular fluid of patients with
juvenile periodontitis were relatively resistant to
tetracycline inhibition: the IC50 for
doxycycline and
CMT-1 were 280 and 500 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)