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Titolo:
DOXYCYCLINE INHIBITS NEUTROPHIL (PMN)-TYPE MATRIX METALLOPROTEINASES IN HUMAN ADULT PERIODONTITIS GINGIVA
Autore:
GOLUB LM; SORSA T; LEE HM; CIANCIO S; SORBI D; RAMAMURTHY NS; GRUBER B; SALO T; KONTTINEN YT;
Indirizzi:
UNIV HELSINKI,INST DENT,DEPT PERIODONTOL,PB 41,MNNERHEIMINTIE 172 SF-00014 HELSINKI FINLAND UNIV HELSINKI,INST DENT,DEPT PERIODONTOL SF-00014 HELSINKI FINLAND UNIV HELSINKI,DEPT MED CHEM SF-00014 HELSINKI FINLAND SUNY STONY BROOK,DEPT ORAL BIOL & PATHOL STONY BROOK NY 00000 SUNY STONY BROOK,DEPT MED STONY BROOK NY 00000 SUNY BUFFALO,DEPT PERIODONT BUFFALO NY 00000 UNIV OULU,DEPT ORAL SURG & PATHOL OULU FINLAND UNIV HELSINKI,DEPT ANAT HELSINKI FINLAND
Titolo Testata:
Journal of clinical periodontology
fascicolo: 2, volume: 22, anno: 1995,
pagine: 100 - 109
SICI:
0303-6979(1995)22:2<100:DIN(MM>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLYMORPHONUCLEAR LEUKOCYTE COLLAGENASE; CREVICULAR FLUID; INTERSTITIAL COLLAGENASES; BACTEROIDES-GINGIVALIS; TETRACYCLINE INHIBITION; COLLAGENOLYTIC ACTIVITY; JUVENILE PERIODONTITIS; SALIVARY COLLAGENASE; DISEASE PROGRESSION; ELASTASE;
Keywords:
MATRIX METALLOPROTEINASES; GINGIVA; PERIODONTITIS; TETRACYCLINE DOXYCYCLINE-INHIBITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
L.M. Golub et al., "DOXYCYCLINE INHIBITS NEUTROPHIL (PMN)-TYPE MATRIX METALLOPROTEINASES IN HUMAN ADULT PERIODONTITIS GINGIVA", Journal of clinical periodontology, 22(2), 1995, pp. 100-109

Abstract

We previously reported that low-dose doxycycline (DOXY) therapy reduces host-derived collagenase activity in gingival tissue of adult periodontitis (AP) patients. However, it was not clear whether this in vivoeffect was direct or indirect. In the present study, inflamed human gingival tissue, obtained from AP patients during periodontal surgery, was extracted and the extracts partially purified by (NH4)(2)SO4 precipitation. The extracts were then analyzed for collagenase activity using SDS-PAGE/fluorography/laser densitometry, and for gelatinase activity using type I gelatin zymography as well as a new quantitative assayusing biotinylated type I gelatin as substrate. DOXY was added to theincubation mixture at a final concentration of 0-1000 mu M. The concentration of DOXY required to inhibit 50% of the gingival tissue collagenase (IC50) was found to be 16-18 mu M in the presence or absence of 1,2 mM APMA (an optimal organomercurial activator of latent procollagenases); this IC50 for DOXY was similar to that exhibited for collagenase or matrix metalloproteinase (MMP)-8 from polymerphonuclear leukocytes (PMNs) and from gingival crevicular fluid (GCF) of AP patients. Of interest, Porphyromonas gingivalis collagenase was also inhibited by similar DOXY levels (IC50=15 mu M), however the collagenase activity observed in the gingival tissue extracts was found to be of mammalian not bacterial origin based on the production of the specific alpha(A) (3/4) and alpha(B) (1/4) collagen degradation fragments. In contrast, the inhibition of collagenase purified from culture media of human gingival fibroblasts (MMP-1) required much greater DOXY levels (IC50 = 280 mu M). The predominant molecular forms of gelatinolytic activity present in the AP patients gingival tissue extracts were found to closely correspond to the 92 kD PMN-type gelatinase (MMP-9) although small quantities of 72 kD fibroblast-type gelatinase (MMP-2), and some other lowmolecular weight gelatinases, were also detected. The IC50 of DOXY versus gingival tissue gelatinolytic activity was estimated at 30-50 mu M measured using either type I gelatin zymography or the biotinylated type I gelatin assay. We conclude that MMPs in inflamed gingival tissue of AP patients, like those in GCF, originate primarily from infiltrating PMNs rather than resident gingival cells (fibroblasts and epithelial cells) or monocyte/macrophages, and that their pathologically-elevated tissue-degrading activities can be directly inhibited by pharmacologic levels of doxycycline.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 03:26:45