Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accelerated periodontal tissue destruction in patients with labile insulin-dependent diabetes mellitus (DM) and localized juvenile periodontitis (LJP) has been suggested to be related to functional abnormalities of neutrophils. We have recently found that collagenase in gingival crevicular fluid (GCF) of adult periodontitis patients is primarily derived from neutrophils and that neutrophil collagenase activity is more sensitive to inhibition by tetracyclines than collagenase produced by fibroblasts. This study is to characterize the cellular sources, activation and inhibition of collagenase in GCF of DM patients and to compare it with collagenase in LJP GCF. We found differences which may have therapeutic implications. Specific doxycycline inhibition tests revealed that GCF collagenase in DM is derived from neutrophils, whereas the enzyme in LJP originates primarily from fibroblasts. Oxidant, sodium hypochlorite, activated efficiently GCF collagenase of DM but not LJP patients. In contrast, plasmin activated LJP GCF collagenase but not that of DM patients. In GCF of DM patients 50-60% of collagenase existed in an active form, whereas in LJP GCF, the enzyme was almost completely in a latent form. The results suggest that collagenase in GCF of periodontitis patients with labile DM is primarily derived from neutrophils and that tetracycline therapy may be an effective adjunct in treatment aimed at controlling the periodontal breakdown in these patients. On the other hand, in LJP the anti-collagenase property of tetracyclines may be less important for control of periodontal tissue destruction because of the tetracycline-resistance of fibroblast collagenase.
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PMID:Cellular source and tetracycline-inhibition of gingival crevicular fluid collagenase of patients with labile diabetes mellitus. 131 30

Mammalian interstitial collagenases (E.C.3.4.24.7) are considered as key initiators of collagen degradation in periodontal diseases. However, the cellular sources of collagenases present in gingival crevicular fluid have not been completely clarified. Resident fibroblasts and epithelial cells as well as infiltrating neutrophils and monocyte/macrophages are potential sources of the enzymes. We have recently found significant differences in tetracycline inhibition between human neutrophil and fibroblast interstitial collagenases. To address the cellular source of collagenase present in gingival crevicular fluid in 2 distinct periodontal diseases, we studied the tetracycline inhibition of collagenase in gingival crevicular fluid of patients with localized juvenile periodontitis and adult periodontitis. Gingival crevicular fluid samples were collected from deep (greater than 5 mm) periodontal pockets and assayed for collagenase in the presence of 0-1000 microM doxycycline as well as a chemically modified tetracycline devoid of antimicrobial activity (4-de-dimethylaminotetracycline). The drug concentration required to inhibit 50% of collagenase activity (IC50) in localized juvenile periodontitis gingival crevicular fluid was 280 microM for doxycycline and 470 microM for 4-de-dimethylaminotetracycline. Significantly lower values, 10-20 microM, were obtained for collagenase in gingival crevicular fluid of patients with adult periodontitis. We propose that systemic tetracycline levels are efficient inhibitors of collagenase in gingival crevicular fluid in affected sites of patients with adult periodontitis but not of patients with localized juvenile periodontitis and that the fibroblast type interstitial collagenase is the predominant collagenase type in gingival crevicular fluid in affected sites of patients with localized juvenile periodontitis and the neutrophil collagenase in adult periodontitis gingival crevicular fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tetracycline inhibition identifies the cellular origin of interstitial collagenases in human periodontal diseases in vivo. 132 40

The lymphocyte populations and subpopulations extracted from inflamed periodontal tissues of patients with adult periodontitis were determined. 34 patients were grouped according to the gingival index score (GI) of 1, 2 and 3. Gingival tissue from 2 involved teeth was excised, treated with collagenase, and infiltrating cells were isolated and identified using monoclonal antibodies for lymphocyte sets and subsets. The % of CD3+ cells was about 54.5% in all 3 patient groups, but the percentage of CD22+ cells increased from 28.9 +/- 3.3% in the group with GI = 1 to 33 +/- 1.2% in the group with GI = 3. %s of CD4+ cells and activated CD4+ cells increased from 30.2 +/- 2.1% and 4.7 +/- 1.7% in the group with GI = 1 to 38.4 +/- 1.2% and 16.0 +/- 3.4% in the group with GI = 3, respectively, while in the same groups, the % of CD8+ cells decreased from 24.9 +/- 2.0% to 17.7 +/- 1.6%. These data indicate a possible importance of activated CD4+ cells in pathogenetic mechanisms of periodontitis.
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PMID:Determination of lymphocyte populations and subpopulations extracted from chronically inflamed human periodontal tissues. 134 55

In view of the important role of fibroblast-type collagenase in the pathogenesis of periodontal disease (PD), we investigated the expression of this metalloproteinase in primary cultures of non-stimulated fibroblasts dissected from gingival tissues of patients with generalized moderate and localized severe chronic adult PD. Enhanced hybridization signals for collagenase RNA were observed in 8/8 PD-cases when compared with equivalent RNA amounts extracted from normal fibroblasts. Since both the proto-oncogene c-fos and the "early growth response" gene egr-1 might be involved in the transcriptional regulation of the collagenase gene expression in vivo, we also compared the relative expression of both potential transcriptional factors with collagenase RNA in the same fibroblast cytoplasmic extracts. Hybridization signals indicated elevated RNA amounts for c-fos in 8/8 PD-cases and for egr-1 in 7/8 PD-cases when compared with the cells from non-inflamed tissue. In periodontitis gingival tissue specimens, immunolocalization of collagenase could be confirmed in fibroblasts, macrophages and epithelial cells in situ. Collagenase label was not widely distributed within the tissues, but concentrated at the interface between epithelium and connective tissue. The data provide the first evidence that gingival fibroblasts producing elevated levels of collagenase RNA amounts express also c-fos and egr-1 indicating a crucial role for both genes in cellular proliferation and collagenase expression in gingival and periodontal tissue destruction in vivo.
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PMID:Expression of collagenase and potential transcriptional factors c-fos and egr-1 in periodontal gingival fibroblasts. 138 1

Activation of latent human fibroblast-type and neutrophil interstitial procollagenases as well as degradation of native type I collagen by supra- and subgingival dental plaque extracts, an 80-kDa trypsinlike protease from Porphyromas gingivalis (ATCC 33277), a 95-kDa chymotrypsinlike protease from Treponema denticola (ATCC 29522), and selected bacterial species commonly isolated in periodontitis was studied. The bacteria included were Prevotella intermedia (ATCC 25261), Prevotella buccae (ES 57), Prevotella oris (ATCC 33573), Porphyromonas endodontalis (ES 54b), Actinobacillus actinomycetemcomitans (ATCC 295222), Fusobacterium nucleatum (ATCC 10953), Mitsuokella dentalis (DSM 3688), and Streptococcus mitis (ATCC 15909). None of the bacteria activated latent procollagenases; however, both sub- and supragingival dental plaque extracts (neutral salt extraction) and proteases isolated from cell extracts from potentially periodontopathogenic bacteria P. gingivalis and T. denticola were found to activate latent human fibroblast-type and neutrophil interstitial procollagenases. The fibroblast-type interstitial collagenase was more efficiently activated by bacterial proteases than the neutrophil counterpart, which instead preferred nonproteolytic activation by the oxidative agent hypochlorous acid. The proteases were not able to convert collagenase tissue inhibitor of metalloproteinase (TIMP-1) complexes into active form or to change the ability of TIMP-1 to inhibit interstitial collagenase. None of the studied bacteria, proteases from P. gingivalis and T. denticola, or extracts of supra- and subgingival dental plaque showed any significant collagenolytic activity. However, the proteases degraded native and denatured collagen fragments after cleavage by interstitial collagenase and gelatinase. Our results indicate that proteases from periodontopathogenic bacteria can act as direct proteolytic activators of human procollagenases and degrade collagen fragments. Thus, in concert with host enzymes the bacterial proteases may participate in periodontal tissue destruction.
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PMID:Identification of proteases from periodontopathogenic bacteria as activators of latent human neutrophil and fibroblast-type interstitial collagenases. 139 63

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)
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PMID:Tetracycline inhibition identifies the cellular sources of collagenase in gingival crevicular fluid in different forms of periodontal diseases. 142 10

Human neutrophil cathepsin G has been identified as a potent proteolytic activator of latent human neutrophil collagenase in vitro. In order to examine the role of cathepsin G in the activation mechanism of latent human neutrophil collagenase in vivo, gingival crevicular fluid was collected from periodontal pockets of patients with adult periodontitis and the relationship of cathepsin G to the proportion of endogenously active collagenase and total collagenase activity was determined. The changes in these parameters were monitored before and after periodontal therapy and compared to control values obtained for periodontal sites without clinical signs of inflammation or increased pocket depth. A significant decrease in cathepsin G and collagenase activity in gingival crevicular fluid collected from initially deep periodontal pockets was observed in response to scaling and root planing (P less than 0.025, Wilcoxon signed rank test). Also the proportion of endogenously active collagenase decreased (P less than 0.05). There was a significant correlation of cathepsin G and total collagenase activity. However, no correlation of cathepsin G activity and endogenously active collagenase was observed. The results indicate the existence of several distinct activation pathways for latent human neutrophil collagenase in vivo and suggest that, apart from cathepsin G, other proteolytic activation cascades and/or non-proteolytic activation pathways participate in the activation of latent human neutrophil collagenase in vivo.
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PMID:Relationship of collagenase and cathepsin G activity in gingival crevicular fluid. 143 26

Traditional clinical variables of periodontal pathology have only limited value as indicators for future disease progression in patients with adult periodontitis. Consequently, other aspects of the periodontal lesion are being examined for their diagnostic utility. Analysis of the host response in gingival crevicular fluid (GCF) is among the most intensely studied of these new diagnostic approaches. Specific indicators of the humoral immune response, cellular immune response, and acute inflammatory response have been identified in GCF. The relationship of indicators of the humoral immune response to active periodontal disease is equivocal. Specific indicators of the cellular immune response in GCF may ultimately prove to be important diagnostically, but the relationship of any specific marker to active periodontal disease has not been reported. In contrast, the acute inflammatory response in GCF has been extensively studied and a number of factors appear to be associated with an increased risk for future disease progression. Indicators of enhanced polymorphonuclear leukocyte activity, (lysosomal beta-glucuronidase, lysosomal collagenase), prostaglandin E2, and an indicator of acute tissue destruction (the cytoplasmic enzymes aspartate aminotransferase) have been associated with the occurrence of clinical attachment loss. An example of the application of a GCF marker in a periodontitis clinical trial is provided by describing the relationship of lysosomal beta-glucuronidase in GCF at baseline and 2 weeks following root planing and scaling to the occurrence of disease activity during the following 6 months. Persistently elevated levels of this enzyme were related to clinical attachment loss. The positive, negative, and total predictive values for beta-glucuronidase as an identifier of clinical attachment loss were 86%, 71%, and 76%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The host response in gingival crevicular fluid: potential applications in periodontitis clinical trials. 147 31

Analysis of inflammatory exudate collected from sites of experimental periodontitis in cynomolgus monkeys has revealed the presence of collagenase and a 92-kDa gelatinase that comigrated after electrophoresis with the 92-kDa gelatinase released from polymorphonuclear leukocytes. Since neutralizing antibodies to fibroblast collagenase had no effect on the collagenase activity and bacterial collagenases could not be detected, polymorphonuclear leukocytes appear to be the major source of collagenolytic proteinases in inflammatory fluid from gingiva.
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PMID:Evidence for polymorphonuclear leukocyte collagenase and 92-kilodalton gelatinase in gingival crevicular fluid. 165 87

Collagenolytic activity (CA) in cervical fluid of patients with inflammation of periodontium was increased with increasing activity of the pathological process. Enhanced CA in patients with severe forms of periodontitis is probably due to depletion of endogenous inhibitors and to the transition of the latent collagenase to its active form. Studies of the effect of EDTA, PMSF and PCMB on CA show that proteinases are an essential factor in inflammation of periodontium.
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PMID:[Proteinases as a pathogenetic factor in inflammatory processes in periodontal tissues]. 166 Jul 39


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