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)

Polymorphonuclear leukocytes (PMNs) have been implicated in the pathogenesis of inflammatory gingivitis and periodontitis. To further study the role of PMNs in mediating gingival injury, we cocultured these cells in vitro with monolayers of human gingival epithelial cells. Scanning electron microscopy revealed that the epithelial cells were homogeneous and SDS-PAGE/immunoblot analysis identified the presence of keratins K3, K13 and the K6/16 pair which authenticated the oral origin of the cells. Injury to the gingival cells was determined by scanning electron microscopy and measurement of cell detachment and cytolysis. Unstimulated PMNs produced minimal lysis or detachment, but PMNs stimulated by phorbol myristate acetate produced marked epithelial cell detachment without lysis, which was time- and PMN-dose-dependent. Supernatants of activated PMNs were similarly effective, indicating that the mediator was a stable soluble substance. Elastase and cathepsin G, two neutral proteases of PMN origin, produced time- and concentration-dependent detachment of gingival epithelial cells, suggesting that these enzymes may mediate this form of injury. In other studies, gingival epithelial cells were exposed to PMN myeloperoxidase (MPO), chloride and glucose plus glucose oxidase (GO) as a hydrogen peroxide (H2O2) generating system. The toxic oxygen species produced by this system caused lysis of the epithelial targets which was dependent on the duration of incubation and the concentrations of MPO and GO. Azide, an inhibitor of MPO, and catalase, a scavenger of H2O2, inhibited the lytic activity of this system. Scanning electron micrographs of gingival epithelial cells cocultured with activated PMNs showed lifting of the cells from the plating surface, while target cells attacked by the MPO system revealed extensive damage of cell membranes. These studies indicate that activated PMNs cause nonlytic detachment injury to gingival epithelial cells which may be mediated by digestion of their extracellular matrix by granule neutral proteases. Furthermore, PMN MPO is capable of generating toxic oxygen species which can lyse these epithelial cells. Collectively, these actions could have profound adverse effects on the function and integrity of the gingival epithelium.
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PMID:Neutrophil-mediated damage to human gingival epithelial cells. 131 Oct 41

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

Interstitial collagenases (matrix metalloproteinase-1, EC 3.4.24.7), isolated from extracts of inflamed human gingiva, gingival crevicular fluid and saliva were characterized for their molecular weight, proteolytic and non-proteolytic activation and substrate specificity against soluble collagen types I, II and III. All three collagenases had Mr of 70 K. The enzymes existed predominantly in a latent form that could be activated by aminophenylmercuric acetate, gold thioglucose and hypochlorous acid. Among serine proteases tested, trypsin, chymotrypsin, neutrophil cathepsin G and a combination of trypsin and human gingival fibroblast prostromelysin activated gingival and salivary interstitial collagenases. Plasmin and plasma kallikrein, however, were relatively ineffective activators. The collagenases degraded soluble type I and II collagens at apparently equal rates but considerably faster than they did type III collagen. These findings suggest that the characteristics of interstitial collagenases found in inflamed human gingiva, gingival crevicular fluid and saliva are consistent with those of human neutrophil interstitial collagenase rather than the fibroblast-type interstitial collagenase. Thus, neutrophils are suggested to be the main source of such enzymes in inflamed human gingiva, crevicular fluid and saliva during adult periodontitis.
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PMID:The role of gingival crevicular fluid and salivary interstitial collagenases in human periodontal diseases. 196 17

Dental plaque is the major aetiological factor in periodontal diseases and contains several proteolytic enzymes. The origin of these proteinases is, however, poorly studied. This study was undertaken to characterize collagenase present in dental plaque of adult periodontitis patients. Vertebrate-type rather than bacterial-derived collagenase activity was detected in extracts of both supra- and subgingival dental plaque extracts of adult periodontitis patients. Dental plaque collagenase was found to exist predominantly in autoactive form. Dental plaque collagenase from periodontally healthy individuals existed in latent from. Latent dental plaque collagenase from periodontitis lesions could be activated by a 95 kD chymotrypsin-like proteinase from Treponema denticola and human leukocyte cathepsin G but not by human plasmin. Incubation of purified latent leukocyte collagenase with whole cells of Fusobacterium nucleatum, Eubacterium saburreum, Prevotella buccae and Porphyromonas gingivalis, however, did not result to the activation of the enzyme. Doxycycline in vitro inhibited dental plaque collagenase with an IC50-value of 20 microM. Dental plaque collagenase degraded more efficiently type I and II collagens than type III collagen. Western-blot analysis with specific anti-human neutrophil collagenase-antibody revealed that both in supra- and subgingival dental plaque extracts dental plaque collagenase had undergone proteolytic conversion from an 80 kD proform to a 58 kD active form which is associated with catalytic autoactivity as measured by functional collagenase assay. This reflects proteolytic activation of leukocyte collagenase in dental plaque probably by other proteases derived from potent periodontopathogenic bacteria such as T. denticola or other PMN proteases such as cathepsin G.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular source, activation and inhibition of dental plaque collagenase. 759 2

The levels of cathepsin G in gingival crevicular fluid (GCF) from chronic adult periodontitis patients and experimental gingivitis subjects were determined both by activity measurement using N-benzoyl-(DL)-phenylalanine-2-naphthyl ester as a substrate and by enzyme immunoassay using anti-human cathepsin G IgG. The activity level of cathepsin G in GCF of both periodontitis and experimental gingivitis has no significant correlation with all measured clinical parameters. Western immunoblotting using antibodies specific for cathepsin G or alpha 1-proteinase inhibitor revealed that the difficulty in demonstrating the association of its activity with the severity of these diseases was due largely to formation of the enzyme-inhibitor complexes. By contrast, statistically significant positive correlation was found between cathepsin G content in GCF of periodontitis, which was determined by enzyme immunoassay, and such clinical parameters as the GCF volume, the gingival index and probing depth. The increased cathepsin G content with increasing severity of periodontal inflammation was markedly diminished by the initial treatment. Although no significant activity was detectable in GCF of experimental gingivitis, a rapid increase of the immunoreactive cathepsin G was found in GCF at 3-5 d after refraining from oral hygiene measures, which rapidly decreased by 10 d. The progressively increased cathepsin G between 10th and 21st d rapidly decreased by cleaning of the teeth. The results indicate that cathepsin G is involved in the host's defensive mechanism against the invasion of etiologic microbes and/or the development of either periodontitis or gingivitis.
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PMID:Identification and possible function of cathepsin G in gingival crevicular fluid from chronic adult periodontitis patients and from experimental gingivitis subjects. 772 46

The purpose of this study was to evaluate whether the reduced microbicidal activity of polymorphonuclear leukocytes (neutrophils) in patients with early-onset periodontitis is associated with a deficiency of nonoxidative microbicidal proteins. Neutrophils from 10 patients with early-onset periodontitis and 8 healthy control subjects were assessed for elastase isozymes 1 through 4, cathepsin G isozymes 1 through 4 and defensins (HNP-1, HNP-2 and HNP-3) using cationic and acid urea polyacrylamide gel electrophoresis. The results showed that both the total content and the relative distribution of elastase and cathepsin G isozymes was normal in neutrophils of patients with early-onset periodontitis. However, the HNP-3 content was significantly reduced in neutrophils from patients with generalized early-onset periodontitis. These findings indicate that the impaired microbicidal activities of neutrophils in patients with early-onset periodontitis does not appear to be based on an elastase or cathepsin G abnormality in neutrophils. Due to the high variability of HNP-1 + 2 and HNP-3 in neutrophils of control subjects, the reduced HNP-3 content in neutrophils probably plays a minor role in the pathogenesis of generalized early-onset periodontitis.
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PMID:Neutrophil lysosomal nonoxidative microbicidal proteins in early-onset periodontitis. 780 68

The presence, localization and activities of cathepsin G in gingival tissue specimens and crevicular fluid (GCF) from 9 adult periodontitis patients and 6 controls with clinically healthy periodontium were studied by use of avidinbiotin-peroxidase complex method, Western and dot blotting, and spectrophotometric activity assay. In contrast to healthy gingival tissue specimens, gingival tissue specimens collected from adult periodontitis patients contained inflammatory cells in lamina propria, beneath the oral sulcular epithelium, 10-50% of which were cathepsin G positive polymorphonuclear neutrophilic leukocytes (PMNs) and monocyte/macrophage-like cells. Cathepsin G activities were increased in adult periodontitis GCF when compared to periodontally healthy controls' GCF (p < 0.05). In adult periodontitis GCF, Western blotting disclosed free cathepsin G but also clear complexes of cathepsin G with its predominant endogenous inhibitor alpha 1-antichymotrypsin (alpha 1-ACT). The present results demonstrate that part of the cathepsin G, despite the presence of increased concentrations of alpha 1-ACT, was in an uncomplexed, free and functionally active form. Our results suggest that GCF cathepsin G reflects the disease process in adjacent inflamed gingiva and also increased host response to microbiota and/or dental plaque in the periodontitis lesions. Cathepsin G may contribute to periodontal tissue destruction directly and indirectly, via proteolytic activation of latent neutrophil procollagenase (promatrix metalloproteinase-8 [proMMP-8]).
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PMID:Cathepsin G in gingival tissue and crevicular fluid in adult periodontitis. 884 41

Five host-response indicators were measured by enzyme-linked immunosorbent assays on unstimulated whole saliva samples from 45 adults (19 male, 26 female). The participants were distributed among four dentate groups representing oral health (I), gingivitis (II), moderate periodontitis (III), and severe periodontitis (IV), and one group of edentulous volunteers (V). Levels of the host-response indicators varied widely, from zero, primarily with groups I and V, to relatively high values with groups II, III and IV. The levels ranged as follows: alpha 2-macroglobulin, 0-4941 ng/ml; alpha 1-antitrypsin, 2-2271 ng/ml; C-reactive protein, 0-472 pg/ml; cathepsin G, 0-6035 ng/ml; elastase, 0-164 ng/ml (free), 0-732 ng/ml (bound to alpha 1-antitrypsin), and 0-318 ng/ml (bound to alpha 2-macroglobulin). Statistical evaluation by planned contrasts showed that levels of host-response indicators for group I were significantly lower (except for alpha 1-antitrypsin) than for groups II, III, and IV. A trend analysis of groups I-IV showed that mean scores (again, except for alpha 1-antitrypsin) increased significantly in a positive, monotonic manner. Group V showed significantly lower values for elastase than in the other groups. The findings demonstrate that these factors can be detected in whole saliva and suggest that, except for alpha 1-antitrypsin, their levels are directly related to an individual's periodontal status.
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PMID:Salivary levels of alpha 2-macroglobulin, alpha 1-antitrypsin, C-reactive protein, cathepsin G and elastase in humans with or without destructive periodontal disease. 885 Jun 55

Tissue destruction during periodontitis is believed to be primarily brought about by leukocyte proteinases. We postulate that oral spirochetes cause discharge of polymorphonuclear leukocyte (PMN) lysosomal enzymes. Effects of Treponema denticola 53-kDa outer membrane protein, lipopolysaccharide (LPS), and peptidoglycan on degranulation of matrix metalloproteinases (MMP)-8 (collagenase) and -9 (gelatinase), cathepsin G, and elastase by human peripheral blood PMNs were studied by specific enzyme assays and Western blot analysis. T. denticola 53-kDa kDa outer membrane protein was found to be a particularly efficient inducer of MMP-8 release. The induction was comparable with that of phorbol myristate acetate, a known inducer of PMN specific granule discharge. All of the treponemal substances, most notably the 53-kDa protein and LPS, induced release of MMP-9, a component of C-type granules. Both collagenase and gelatinase released from PMNs were mostly in active forms. Release of cathepsin G and elastase was also observed with the 53-kDa protein treatment. The other T. denticola substances did not induce release of these serine proteinases. Lactate dehydrogenase was not released from PMNs by the treatments, indicating that the degranulation was specific and not caused by toxic effects of the substances. This was confirmed by transmission electron microscopy of PMNs treated with the 53-kDa protein that showed rapid vacuole formation and cell shape changes but no disintegration of the cells. Thus, T. denticola may participate in the PMN-dependent extracellular matrix degradation during the course of periodontal inflammation by triggering the secretion and activation of matrix metalloproteinases.
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PMID:Membrane components of Treponema denticola trigger proteinase release from human polymorphonuclear leukocytes. 903 54

Cathepsin G and medullasin are 2 major serine proteinases associated with the granular fraction of polymorphonuclear leukocytes (PMNs). To know their possible involvement in the pathophysiological gingival connective tissue turnover, we have determined the distribution and localization of these 2 enzymes in inflamed gingival tissues from periodontal patients by immunohistochemistry with discriminating antibodies specific for each enzyme. The gingival connective tissues were obtained from periodontitis patients with various inflammatory conditions and control healthy subjects without any clinical signs of periodontal inflammation. In all gingival specimens examined, cathepsin G and medullasin were found mainly in neutrophil-like cells and partly in macrophage-like cells. No positive staining for both enzymes was obtained in endothelial cells and fibroblasts in every part of the gingival tissues. Immunoreactivity for each enzyme in the gingival tissues from the periodontitis group was stronger and greater in the intensity and frequency than that from the control group and appeared to be increased with the severity of the disease In both groups, the number of immunoreactive cells for each enzyme was greater in the vicinity of pocket epithelium (zone I) than in the area of central connective tissue (zone II) or the area subjacent to the oral epithelium (zone III). While both enzymes in zones II and III were exclusively found in coarse granules, their stainings in zone I were not only coarse but also diffuse. These results strongly suggest that both enzymes may have some association with inflamed gingival tissue degradation.
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PMID:Immunohistochemical study of cathepsin G and medullasin in inflamed gingival tissues from periodontal patients. 908 94


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