UMLS:C0031099 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0031099 (periodontitis)
12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During earlier examination of interleukin-1 (IL-1)-induced matrix metalloproteinase gene expression in human gingival fibroblasts a highly induced immediate early gene, I kappa B-alpha, a NF kappa B DNA-binding inhibitor, was identified. The aim now was to investigate whether recombinant (r)IL-1 beta induces the stimulation of NF kappa B and its inhibitor proteins in human gingival fibroblasts and to understand if inhibition of its activity affects collagenase gene expression. Primary gingival fibroblasts (human) were treated with rIL-1 beta to determine the effect on NF kappa B-like DNA-binding activity. IL-1 induced the production of steady-state mRNA levels of I kappa B-alpha in the cultured fibroblasts. Nuclear run-on transcription studies demonstrated that rIL-1 induction of I kappa B-alpha may be transcriptionally regulated. Using electrophoretic mobility gel-shift assays it was shown that rIL-1 activates NF kappa B-like, DNA-binding activity in these fibroblasts. NF kappa B-like DNA-binding activity was rapidly induced and turned over in gingival fibroblasts with peak activity at 30 min after rIL-1 treatment. Further, treatment with chymotrypsin protease inhibitor and antioxidant inhibitor prevented IL-1-induced, NF kappa B-like, DNA-binding activity and collagenase mRNA production. When coupled with the existence of NF kappa B consensus DNA-binding sites on the collagenase gene promoter, these findings suggest that the stimulation of NF kappa B in gingival fibroblasts by rIL-1 could play an important part in the regulation of their collagenase gene expression. The ability of IL-1 to stimulate this expression may define a pivotal role for this cytokine in the pathogenesis of periodontitis.
...
PMID:Association of interleukin-1-induced, NF kappa B DNA-binding activity with collagenase gene expression in human gingival fibroblasts. 880 9

Previous observations suggest that interleukin-1 (IL-1) may play an important role in the progression of periodontitis. In the present study, we investigated whether a cell-associated IL-1 alpha (CAIL-1 alpha) produced in human gingival fibroblasts (HGF) induces biological activities related to the progression of periodontitis. HGF were treated with recombinant human IL-1 beta (rhIL-1 beta) for 12 h. After that, the cell layers of HGF were washed 3 times with fresh medium and were then fixed with 1% paraformaldehyde. The fixed cell layers of HGF were used for assays for bone resorbing activity, prostaglandin E2 (PGE2) production and collagenase activity. Fixed cell layers of HGF treated with rhIL-1 beta enhanced not only calcium release from BALB/c mouse calvaria but also PGE2 production and collagenase activity in HGF and human periodontal ligament fibroblasts (HPLF) cultured on the fixed cell layers. These activities were neutralized by treatment with monoclonal mouse anti-human IL-1 alpha antibody, but monoclonal mouse anti-human IL-1 beta antibody showed no effects on these activities. The induction of these activities by fixed cell layers of HGF required direct contact between the fixed cell layers and the calvaria, HGF, or HPLF. These results suggest that CAIL-1 alpha produced in HGF treated with rhIL-1 beta induces bone resorbing activity, PGE2 production and collagenase activity in the target cells by direct contact; CAIL-1 alpha may play an important role in the progression of periodontitis.
...
PMID:Interleukin-1 alpha produced in human gingival fibroblasts induces several activities related to the progression of periodontitis by direct contact. 885 40

Previous studies have shown increased susceptibility to periodontal diseases in children with Down's syndrome (DS). The mechanisms involved in the periodontal inflammatory processes in DS are not fully understood. The present study characterized the periodontal status of 9 non-institutionalized DS children 9 to 17 years old (mean 13.6 years) relative to their age-matched systemically and periodontally healthy controls. The periodontal status was assessed by visible plaque index (VPI), gingival bleeding index (GBI), and probing depth. We also assessed, by sodium dodecyl sulphate polyacrylamide gel electrophoresis/laser densitometry and by zymography, the collagenase and gelatinase activities in the gingival crevicular fluid (GCF) and saliva samples collected from DS patients and from the controls. Eight of the nine DS children showed a periodontium comparable to that seen in healthy controls; beginning alveolar bone loss was radiographically seen in the DS patient with deep periodontal pockets. The endogenously active collagenase and total collagenase activities were slightly higher in GCF of DS children compared to healthy controls. Western blot demonstrated that GCF collagenase of DS patients was human neutrophil collagenase (MMP-8 or collagenase-2), which occurred in 75 kDa proMMP-8 and in DS patients, but not in controls, also in 65 kDa active MMP-8 form and occasionally lower 40-50 kDa MMP-8 species. Zymographic analysis revealed the presence of 120 kDa (MMP-9 complexed with neutrophil gelatinase associated lipocalin or NGAL), 92 kDa (MMP-9) and 72 kDa (MMP-2) gelatinases in DS and control GCF. Especially in DS GCF MMP-9 occurred in part in 82-85 kDa activated form. Salivary collagenase in DS was high when compared to controls but of the same MMP-8 type as in control saliva. Our findings suggest that in vivo activated MMP-8 in GCF derived from triggered PMNs and/or cytokine-induced periodontal fibroblasts may reflect periodontal tissue and alveolar bone destruction seen in the early stages of gingivitis/periodontitis associated with Down's syndrome.
...
PMID:Characterization of matrix metalloproteinase (MMP-8 and -9) activities in the saliva and in gingival crevicular fluid of children with Down's syndrome. 886 13

The Porphyromonas gingivalis collagenase-specific serum immunoglobulin A (IgA), IgM, and IgG responses from 20 patients with early-onset periodontitis (EOP), 20 patients with adult periodontitis, (AP), and 20 age- and sex-matched healthy controls were examined by immunoblot analysis. A recombinant collagenase antigen used for the immunoblot analysis was produced by using the plasmid pGEX-2T, which allows the fusion between the collagenase and glutathione S-transferase. There was no significant difference in collagenase-specific IgG antibody detection between samples from the EOP, AP, and control groups. In contrast, 85% of AP and EOP sera had collagenase-specific IgA antibodies, whereas only 20% of control sera showed collagenase-specific IgA reactivity. Plaque samples from all groups were assessed by PCR with primers complementary to the collagenase-encoding gene prtC. The results indicated that 90% of AP and EOP plaque samples and 10% of control samples were positive for P. gingivalis. All patients with collagenase-specific IgA antibodies were PCR positive. The results of the study indicate a nearly complete concordance (k = 0.856) between the presence of collagenase-specific IgA antibodies and PCR detection of P. gingivalis. By using PCR as the "gold standard," the sensitivity and specificity of the IgA immunoblot test were 94.7 and 90.9%, respectively. Therefore, the recombinant collagenase is a potential candidate for use in the serodiagnosis of periodontitis.
...
PMID:Serodiagnosis of Porphyromonas gingivalis infection by immunoblot analysis with recombinant collagenase. 888 Apr 90

Numerous data strongly suggest the involvement of cytokines and the matrix metalloproteinase collagenase (MMP-1) in the pathogenesis of periodontitis. Recently, we have demonstrated that, upon culturing under the influence of IL-1 alpha + EGF, a large amount of inactive procollagenase (MMP-1) is stored in the extracellular matrix of periosteal tissue. We now show that this endogenous reservoir of proenzyme can be operative after activation with plasmin and is able to induce a rapid and almost complete breakdown of the collagenous extracellular matrix. The level of collagen degradation following activation showed a strong correlation with the amount of proenzyme that was incorporated in the tissue. The highest level of degradation (70% of the total amount of collagenous proteins) was found with the IL-1 alpha + EGF-treated explants, followed by those treated with IL-1 alpha alone (35%). Explants cultured with EGF or in the absence of cytokines, containing only small amounts of procollagenase, showed little collagen breakdown following plasmin activation (7%). Inhibition of metalloproteinases by EDTA, or blockage of plasmin by PMSF, prevented the degradation in all explants irrespective of the amount of proenzyme present in the tissue. Our findings demonstrate that endogenous proenzyme stored in a native connective tissue matrix can be activated at a later time interval which results in a massive breakdown of the tissue. This study shows a possible pathway of collagenase-induced breakdown without recent de novo synthesis of the enzyme. Such a sequence may be operative in chronic inflammatory diseases, such as periodontitis, where production of procollagenase under the influence of cytokines spans a longer time period, whereas breakdown is often characterized by a cyclic behaviour.
...
PMID:Cytokine-induced endogenous procollagenase stored in the extracellular matrix of soft connective tissue results in a burst of collagen breakdown following its activation. 891 51

The authors, including an academic-inventor, the director of the University's tech-transfer office, and the CEO of a "start-up" pharmaceutical company based on the professor's (and his colleague's) inventions, relate the history and current status of their interactions. To start, the basic research leading to the "eureka" experiment (such things really do happen) is summarized: namely, the discovery of (i) the surprising ability of the tetracycline antibiotics to inhibit mammalian tissue-destructive proteinases (collagenase, gelatinase) during a variety of disease processes, e.g., periodontitis, the arthritides, osteopenia/osteoporosis, sterile corneal ulcers, tumor invasion/metastasis/angiogenesis, and (ii) a series of chemically-modified, non-antibacterial analogs of tetracyclines to inhibit these enzymes without producing typical antibiotic side effects. The role of the University in obtaining the services of patent attorneys, and its assistance in developing the strategy to deal with an industrial partner, is addressed. Above all, the authors stress the need for close cooperation and collegial interactions between all three groups in this high-risk (but potentially high-benefit-to-the-public) enterprise.
...
PMID:New therapeutic uses for an old family of drugs: travels of a dental researcher from the lab to the university's office of technology transfer and beyond. 893 Dec 41

Immunomodulation by periodontopathic bacteria has been implicated in the pathogenesis of inflammatory periodontal diseases. A novel class of microbial-derived T cell mitogens, referred to as superantigens, has recently been described. Superantigens are unique in that they induce a tremendous activation and expansion of specific subsets of T cells in an antigen-independent manner, thereby causing immune dysfunction. Subsets of superantigen-expanded T cells can be identified with reagents that discriminate among different families of the variable domains of the T cell antigen receptor beta-chain (V beta). Since superantigens expand one or a few of these T cell antigen receptor V beta families, T cell subsets that have been expanded by superantigens have restricted expression of one or a few V beta families. In the present study, we investigated the presence of putative superantigen-stimulated T cells in periodontitis sites, utilizing a panel monoclonal antibodies to T cell antigen receptor V beta families. Leukocytes were isolated from gingival tissues obtained from 8 periodontitis and 4 non-periodontitis patients by collagenase digestion. Three-color flow cytometric analysis of these gingival cells demonstrated that in most periodontitis patients examined, patterns of V beta expression among T cells are characteristic of superantigen stimulation, i.e., there is an elevation in the proportion of one or a few V beta families. Specifically, these analyses revealed that T cell subsets expressing V beta 5a and V beta 5b, V beta 6, V beta 8 and V beta 12 were each elevated greater than 2 standard deviations in at least one periodontitis patient compared with the mean of the non-periodontitis subjects. In some periodontitis patients, a less marked elevation of T cells that express V beta 3, V beta 5a, V beta 5b, V beta 6, V beta 8, V beta 12, and V beta 13 was noted (greater than 1 standard deviation higher than the mean of the V beta families in non-periodontics subjects). Interestingly, V beta 8+ T cells were elevated to some degree in all periodontitis patients examined. In contrast, T cells expressing V beta 2, V beta 17 and V beta 19 were not significantly different in any of the subjects studied. In most periodontitis but not non-periodontitis patients, up to 50% of all gingival T cells expressed one or a few T cell antigen receptor V beta families, suggesting that superantigens constitute a major pathway of T cell activation and expansion. Hence, our data support the hypothesis that a large proportion of T cells in periodontitis sites have been stimulated and expanded by superantigens, presumably produced by periodontitis-associated bacteria.
...
PMID:Evidence for involvement of superantigens in human periodontal diseases: skewed expression of T cell receptor variable regions by gingival T cells. 894 59

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.
...
PMID:Matrix metalloproteinases and their inhibitors in gingival crevicular fluid and saliva of periodontitis patients. 899 58

Interstitial collagenases, including matrix metalloproteinase-1 (MMP-1) and -8 (MMP-8), serve as initiators of extracellular matrix destruction in periodontal disease. Collagenase activities are mainly regulated by tissue inhibitors of metalloproteinases (TIMPs). We tested the effects of inflammation on MMP-1 and MMP-8 gene expression in periodontal disease. To determine the relative abundance of these mRNAs in gingiva, we used a reverse transcription-polymerase chain reaction (RT-PCR) assay. Gingival biopsies were divided into 2 groups; a control group and an inflamed group with severe gingivitis or periodontitis. The MMP-1 mRNA levels were significantly elevated in inflamed gingiva, while the levels of the MMP-8 transcript were not different in the 2 groups and barely detectable by RT-PCR assay. The expression of the TIMP-1 gene was not altered, and remained higher than any of these other genes in both control and diseased gingivae. These results suggest that MMP-1 rather than MMP-8 may play an important role in the initiation of collagen degradation in periodontal disease. However, the possibility remains that MMP-8 plays an important role in periodontal tissue destruction, since the mRNA abundance and not the enzyme activity was assessed.
...
PMID:Matrix metalloproteinases-1 and -8 and TIMP-1 mRNA levels in normal and diseased human gingivae. 902 26

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.
...
PMID:Membrane components of Treponema denticola trigger proteinase release from human polymorphonuclear leukocytes. 903 54

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>