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)

In previous studies, elevations in the levels of active and latent collagenase in gingival crevicular fluid (GCF) have been correlated positively with periodontal disease activity. To provide a simple diagnostic approach for testing collagenolytic activity, the feasibility of using a 3.0 ml water mouthrinse to collect GCF simultaneously from all sites in the mouth was assessed. Patients with adult periodontitis (AP, n = 23) and local juvenile periodontitis (LJP, n = 7) were sampled before periodontal therapy and some (12 AP, 4 LJP) were also assessed longitudinally after scaling and root planing, administration of antibiotics, and following periodontal surgery. Healthy patients (n = 19) were used as controls. The levels of active collagenase, procollagenase, and collagenase inhibitor activity were determined by functional assays and quantitated after SDS-PAGE and fluorography. Gelatinase and progelatinase were assayed by enzymography on gelatin-substrate gels. Active collagenase levels were found to be significantly higher (14- to 20-fold) in AP and LJP patients compared to controls, whereas matrix metalloproteinase activity was not detected in mouthrinses from edentulous patients. Collagenase inhibitor levels were generally low in all groups of subjects tested. Following clinical treatment the levels of active collagenase and gelatinase were reduced; the reduction was significant for active collagenase after tetracycline treatment and scaling in LJP patients. Of the clinical indices recorded (gingival index, plaque index, and pocket depth) there were no significant correlations with enzyme activity but similar trends were observed between the changes in active collagenase and gingival index. In patients with untreated periodontal disease, collagenase occurred predominantly in the active form. N-ethylmaleimide (NEM) and p-aminophenylmercuric acetate (AMPA) were equally effective as activators of the latent collagenase, indicating that the collagenase was derived from PMNs, which were also the source of gelatinase. The results of these studies indicate that measurement of active collagenase and gelatinase in mouthrinse samples is potentially useful in the diagnosis and assessment of periodontal disease activity.
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PMID:Identification of polymorphonuclear leukocyte collagenase and gelatinase activities in mouthrinse samples: correlation with periodontal disease activity in adult and juvenile periodontitis. 217 Jun 17

Eight adult periodontitis (AP) patients were studied immunohistochemically to determine the presence of matrix metalloproteinases (MMPs) MMP-1, MMP-3, and MMP-8 in the marginal gingival and gingival granulation tissue specimens obtained from periodontal flap surgery after scaling and root planing. Clinically healthy gingival tissue specimens obtained from impacted third-molar extraction operations served as controls. MMP-type-specific antisera were applied by the avidin-biotin-peroxidase complex staining method. Moderate immunoreactivity for neutrophil collagenase (MMP-8) was found both in the AP patients' marginal gingival connective tissue and in gingival granulation tissue specimens. Immunoreactivity for fibroblast-type collagenase (MMP-1) and stromelysin-1 (MMP-3) was detected only in the AP patients' gingival granulation tissue specimens. In the control specimens, no immunoreactivity for the MMPs could be detected. For the first time, this finding demonstrates immunohistochemically the presence of MMP-8 in human inflamed gingiva in situ, and further highlights the importance of MMP-8 in periodontal tissue destruction, evidently during the acute phase(s) of the disease. However, our results confirm and extend previous studies indicating that other types of MMPs from resident gingival cell sources also seem to participate in the chronic and destructive course of periodontal inflammation.
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PMID:Immunohistochemical study of neutrophil- and fibroblast-type collagenases and stromelysin-1 in adult periodontitis. 787 57

Human gingival fibroblasts were treated with recombinant interleukin-1 (IL-1) to determine the effect of this stimulus on the relative expression of collagenase (MMP-1), stromelysin (MMP-3) and plasminogen activator (PA) mRNA. The steady-state mRNA levels for these genes were determined on Northern blots. IL-1 induced steady-state levels of these mRNAs to different extents. Nuclear run-on transcription studies showed that IL-1 induction of neutral metalloproteinase may be transcriptionally regulated. Actinomycin D and protein kinase inhibitors decreased the mRNA production for all three metalloproteinases, whereas cycloheximide decreased the production of collagenase and stromelysin mRNA. Protein kinase inhibitors (H7/H8) decreased production of the three mRNAs to different extents. This study demonstrates a potentially important role for IL-1 in the regulation of metalloproteinase expression in human gingival fibroblasts. The ability of IL-1 to induce the expression of stromelysin, collagenase and PA may define a pivotal role for this cytokine in the pathogenesis of periodontitis.
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PMID:Mechanistic features associated with induction of metalloproteinases in human gingival fibroblasts by interleukin-1. 798 Jan 14

It is known that the host responds to an increased concentration of collagenase [or matrix metalloproteinase (MMP)-1] by preferentially expressing mRNA for the tissue inhibitor of metalloproteinase-1 (TIMP-1) in order to overcome tissue destruction due to periodontitis. To further elucidate the relation between MMPs and TIMPs in periodontitis-affected tissues, the expression of mRNA for MMP-1, -3 and -8, and TIMP-1 and -2, in 10 gingival samples from patients and five from healthy individuals was assessed by reverse transcription-polymerase chain reaction. The diseased group showed significantly higher levels of MMP-1, -3, -8 and TIMP-1 mRNA relative to beta-actin than the control group (mean +/- SE: diseased vs healthy (%): 0.26 +/- 0.05 vs 0.018 +/- 0.0040 for MMP-1; 0.09 +/- 0.16 vs 0.063 +/- 0.016 for MMP-3; 0.068 +/- 0.017 vs 0.006 +/- 0.0010 for MMP-8; 12.66 +/- 2.90 vs 2.71 +/- 0.54 for TIMP-1; p < 0.01). TIMP-2 did not significantly differ between the two groups (1.79 +/- 0.33 vs 1.42 +/- 0.53; p > 0.05). The preferential increase in the level of MMP-3 mRNA relative to that of MMP-1 and -8 in inflamed gingiva would be relevant to tissue destruction because MMP-3 is a broad-spectrum MMP and a pivotal activator of latent MMP-1 and -8. Therefore, the overall increase in MMP-1, -3 and -8 mRNA in periodontitis-affected gingiva might account for a concerted action of MMPs during connective tissue destruction in periodontitis.
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PMID:Expression of mRNA for matrix metalloproteinases and tissue inhibitors of metalloproteinases in periodontitis-affected human gingival tissue. 873 11

The proteolytic erosion of the temporal bone is the key event in the pathognomonic course of cholesteatoma progression. The molecular mechanisms of bone resorption, endangering the ossicles, the inner ear, the facial nerve, large vessels or the brain, are not understood. Recently, a new family of proteolytic enzymes, the matrix-metalloproteinases (MMP's) has been described and identified, which seems to play a pivotal role in matrix- and bone homeostasis and inflammatory osteolytic diseases, e.g. osteoarthritis and periodontitis. These enzymes are sophisticatedly controlled by specific inhibitors and activation cascades. We investigated whether human cholesteatoma tissue expresses MMP's and MMP-inhibitors. By immunocytochemistry of cholesteatoma-cryosections, the expression of MMP-2 (72 kD collagenase), MMP-9 (92 kD collagenase), and MMP-3 (stromelysin-1) could be seen to be strictly confined to the basal and suprabasal cell layer of the cholesteatoma epithelium. The neutrophil collagenase (MMP-8) showed a more disseminated expression in the epithelium and the granulation tissue as well. The tissue inhibitor of metalloproteases, TIMP-1, could be detected only in very limited areas of the granulation tissue in a quite randomized manner. Therefore, a derailment in favor of proteolysis of the normally tightly controlled MMP-system might be postulated. The results indicate that members of the MMP-family could play an active role in the molecular mechanisms of cholesteatoma invasion into the temporal bone. This offers new insights into the pathophysiology of the disease and of potential therapeutic approaches.
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PMID:Expression of matrix-metalloproteinases and their inhibitors in human cholesteatomas. 879 Jul 47

Matrix metalloproteinases (MMPs) and serine proteinases seem to be related to tissue destruction in periodontitis. The presence of MMPs in gingival crevicular fluid (GCF) and saliva, however, has not been studied comprehensively with the enzyme-linked immunosorbent assay (ELISA)-technique. We therefore examined the levels of MMP-1, -3, -8 and -9, and their endogenous inhibitor, tissue inhibitor of matrix metalloproteinases (TIMP-1), in GCF and saliva of patients with adult periodontitis (AP) and localized juvenile periodontitis (LJP). Elevated levels of MMP-1 were detected in LJP GCF compared to AP and control GCF. Elevated levels of TIMP-1 were also detected in LJP GCF in comparison to AP and control GCF. Higher MMP-8 levels were detected in AP GCF compared to LJP and control GCF. The relative low levels of MMP-3 were present in all studied GCF samples. Elevated levels of MMP-8 were further detected in saliva of AP compared to LJP and the controls. Both MMP-1 and TIMP-1 were detected in all studied saliva samples, but not significant differences were detected between the studied groups. Our ELISA-results confirm that (i) PMN MMP-8 and MMP-9 are the main collagenase and gelatinase in AP GCF, whereas GCF collagenase in LJP seems to be of the MMP-1-type; (ii) only low levels of TIMP-1, endogenous MMP-inhibitor, are present in AP GCF, which emphasises the importance of doxycycline as a possible adjunctive drug in the treatment of AP patients; (iii) tests based on specific antibodies against PMN MMPs, especially MMP-8, might serve as a reliable method of measuring and monitoring enzyme levels in GCF from different periodontitis patients.
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PMID:Matrix metalloproteinases and their inhibitors in gingival crevicular fluid and saliva of periodontitis patients. 899 58

Here, we describe the influence of heparin(s) on the interleukin-1-beta (IL-1beta)-induced expression of collagenase (matrix metalloproteinase-1, MMP-1), stromelysin-1 (matrix metalloproteinase-3, MMP-3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in human gingival fibroblasts (HGF). Amounts of secreted enzymes and inhibitors as well as their mRNA steady-state levels increased significantly following supplementation of HGF culture medium with 2 ng/mL of IL-1 beta1. Addition of heparin to cell culture medium 1 hour following IL-1beta decreased MMP and TIMP-1 expression in a dose-dependent manner. The inhibitory effect of heparin was significant at a concentration as low as 1 microg/mL. These findings could be reproduced with a low Mr heparin fragment devoid of anticoagulant activity. Heparin and fragments might therefore reduce the excessive proteolytic capacity of the gingival fibroblast during inflammation and could be useful as pharmacological agent(s) in gingivitis and periodontitis.
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PMID:Influence of heparin(s) on the interleukin-1-beta-induced expression of collagenase, stromelysin-1, and tissue inhibitor of metalloproteinase-1 in human gingival fibroblasts. 982 76

Stromelysin 1 (MMP-3) is a matrix metalloproteinase with broad substrate specificity that has been linked to joint and tissue destruction associated with chronic inflammatory diseases such as rheumatoid arthritis and periodontitis. Transcription of the stromelysin gene is induced by inflammatory cytokines such as interleukin 1 (IL-1) and tumor necrosis factor as well as a number of other cytokines and mitogens, but the exact mechanisms involved in its regulation are not fully understood. To identify transcription factors and cis elements potentially involved in the IL-1 induction of stromelysin, the human stromelysin 5'-flanking region was screened by electrophoretic mobility shift assay for IL-1-induced DNA-binding complexes in human synovial and gingival fibroblasts. Here we report the identification of such a complex binding to the region -1614 to -1595 (5'-G(T)TTTTTCCCCCCATCAAAG-3') termed the stromelysin IL-1 responsive element site. Binding to this site is also induced by tumor necrosis factor but not by platelet-derived growth factor or interleukin 4. UV cross-linking demonstrates that there are at least two DNA-binding proteins involved, of approximately 48 and 52 kDa. Transient transfection experiments in human foreskin fibroblasts demonstrate that proteins binding to this site act as a repressor of IL-1-induced expression of the stromelysin gene.
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PMID:Identification of a cytokine-induced repressor of interleukin-1 stimulated expression of stromelysin 1 (MMP-3). 989 Sep 74

Chronic periodontitis is a destructive inflammatory disease linked with unbalanced production between matrix metalloproteinases (MMPs), such as interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3) and their endogenous tissue inhibitors of MMPs (TIMPs). In addition to aberrant MMP-1 and MMP-3 expression, periodontal lesions are characterized by dense infiltrations of activated T lymphocytes which may interact with CD40-expressing gingival fibroblasts in the connective tissue via the CD40L-CD40 pathway. In this study we investigated whether CD40 cross-linking influenced MMP production by gingival fibroblasts. Therefore, we analysed the CD40L-induced MMP production by these fibroblasts in the presence of cytokines that are increased in periodontal lesions, such as IL-1beta, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). We show that CD40 ligation on gingival fibroblasts resulted in a decrease of their MMP-1 and MMP-3 production, while MMP-2 and TIMP-1 production were unaffected as determined by Western blot. This down-regulatory effect of CD40 engagement on MMP-1 and MMP-3 production by gingival fibroblasts was also present when MMP production was up-regulated by IL-1beta and TNF-alpha or down-regulated by IFN-gamma. These results suggest that CD40 ligation on gingival fibroblasts leads to a restraining of MMP-1 and MMP-3 production by gingival fibroblasts and thereby may be an important mechanism in the retardation of further periodontal tissue damage.
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PMID:CD40 engagement modulates the production of matrix metalloproteinases by gingival fibroblasts. 993 37

Accumulating evidence indicates that TNFalpha plays an important role in the pathogenesis of periodontitis, but the effect of TNFalpha on the degradation of the periodontal ligament is not well understood. This study used reverse transcriptase-PCR to investigate the effects of TNFalpha on matrix metalloproteinase (MMP) mRNA expression in human periodontal ligament fibroblasts. TNFalpha increased MMP-1, MMP-3 and MMP-13 mRNA levels in both a time-dependent (0-24 h) and a dose-dependent (0.1-10 ng/ml) manner. TNFalpha also increased COX-2 mRNA levels. Because elevation of COX-2 mRNA levels enhances the production of prostaglandins, we therefore investigated whether endogenous prostaglandins are involved in the MMP mRNA expression that is enhanced by TNFalpha. Pretreatment with the selective COX-2 inhibitor, NS-398, increased MMP-13 mRNA levels, while prostaglandin E2 and dibutyryl cyclic AMP decreased MMP-13 mRNA levels. Neither MMP-1 nor MMP-3 mRNA levels were affected by these chemicals. These findings indicate that prostaglandin E2 has a lowering effect on TNFalpha-enhanced MMP-13 mRNA levels, and that this effect is dependent on cAMP. Our results suggest that TNFalpha participates in periodontal ligament destruction by stimulating the production of MMPs (MMP-1, MMP-3 and MMP-13), while endogenous prostaglandin E2 has a negative feedback role in TNFalpha-enhanced MMP-13 production.
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PMID:Effects of TNFalpha and prostaglandin E2 on the expression of MMPs in human periodontal ligament fibroblasts. 1211 50


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