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)

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.
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PMID:Association of interleukin-1-induced, NF kappa B DNA-binding activity with collagenase gene expression in human gingival fibroblasts. 880 9

Expression of mRNA for IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6 and TNF-alpha in inflamed gingiva was quantitatively examined by ribonuclease protection assay and in situ hybridization. The IL-1 beta mRNA expression level was statistically high (P < 0.05) in periodontitis-affected tissues compared with that in gingivitis-affected tissues. The densities of macrophages (identified as CD68-positive cells) and CD45RO-positive cells infiltrating in the inflamed gingiva correlated statistically with IL-1 beta transcript levels (macrophages, P < 0.001; CD45RO-positive cells, P < 0.002). In situ hybridization revealed IL-1 beta mRNA expression in infiltrating cells, presumed to be macrophages. The IL-1 alpha and IL-6 mRNA expression levels were much lower than the IL-1 beta transcript level, and mRNAs for IL-2, IL-4, IL-5 and TNF-alpha were negligible in these gingival tissues. The results indicate that IL-1 beta is a cytokine expressed predominantly in inflamed gingiva and reflects the density of infiltrating macrophages and other leukocytes.
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PMID:IL-1 beta mRNA as the predominant inflammatory cytokine transcript: correlation with inflammatory cell infiltration into human gingiva. 883 19

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.
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PMID:Interleukin-1 alpha produced in human gingival fibroblasts induces several activities related to the progression of periodontitis by direct contact. 885 40

This study presents oral rehabilitation with osseointegrated implants in partially edentulous patients treated for generalized severe adult periodontitis. Five female patients aged between 31 and 44 received a total of 36 implants and were observed for 1 year after insertion of the superstructure. Three months before implantation, venous blood samples were taken from the patients and five periodontally healthy controls, and the serum examined with highly sensitive ELISA test kits for interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6). Clinical examination covered the plaque index (PI) and gingival index (GI) at teeth and implants plus probing depth (PD) and clinical attachment level (CAL) at the teeth. Microbiological evaluation of teeth and implants was performed by dark-field analysis, and DNA analysis was performed in addition 1 year after insertion of the superstructure. Radiological controls of the teeth were carried out with standard single-tooth films in the 2 years preceding implantation and at baseline. Following implantation, further controls of the teeth and implants were undertaken immediately after insertion of the superstructure and 1 year thereafter. The immunological examination revealed that the IL-1 beta (0.22 +/- 0.2 pg/ml) (means +/- SD) and IL-6 (2.27 +/- 2.8 pg/ml) level was slightly, but not significantly, higher in the patients than in the control group (IL-1 beta: 0.06 +/- 0.06 pg/ml and IL-6: 0.64 +/- 0.2 pg/ml) (P > 0.05). The clinical results show that the GI at the teeth rose slightly from 0.0 to 0.2, and at the implants from 0.3 to 0.4. The PI rose slightly from 0.3 to 0.7 at the teeth and from 0.2 to 0.9 at the implants. Neither the GI nor the PI revealed any significant difference between teeth and implants. Clinical attachment loss at the teeth was minimal at 4.7 to 4.8 mm. Comparison between the teeth and the implants revealed no essential difference in bacterial flora; neither Actinobacillus actinomycetemcomitans nor Porphyromonas gingivalis was recorded at any location. Small quantities of Prevotella intermedia were detected at the teeth and implants of one patient. Radiological evaluation 1 year after insertion of the superstructure revealed a mean bone loss of 0.62 mm at the implants. The bone loss at the teeth during the same period was 0.3%, whereas it had been 1.5% in each of the 2 previous years. These results suggest that there is only a slight difference between the periodontal and peri-implant areas in patients with generalized severe adult periodontitis. The full potential for implants in these patients, however, needs to be shown in controlled longitudinal studies.
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PMID:Osseointegrated implants in patients treated for generalized severe adult periodontitis. An interim report. 886 17

Within the in vivo environment human gingival fibroblasts (HGF) may be challenged with bacteria or bacterial products. This interaction may result in the release of cytokines which are directly or indirectly involved in connective tissue and bone catabolism, such as interleukin (IL)-1 beta, IL-6, and IL-8. Our investigation has tested the hypothesis that HGF from Actinobacillus actinomycetemcomitans (Aa)-infected patients with rapidly destructive forms of periodontitis, such as localized juvenile periodontitis (LJP), respond to Aa challenge with an exaggerated secretion of IL-1 beta, IL-6, and IL-8. We have compared the in vitro profiles of these cytokines by Aa-challenged HGF obtained from 2 healthy subjects, 2 Aa-infected, slowly progressing adult periodontitis (AP) patients and 2 LJP patients. HGF were challenged throughout a 48-hour period with formalinized whole bacterial cells, and culture supernatants were analyzed for cytokine content using RIA. No differences were noted in the IL-1 beta secretion levels among the different HGF cultures. Although basal (unchallenged) IL-6 and IL-8 production was similar in all HGF cultures, HGF from the two LJP patients responded to Aa challenge with a more rapid IL-6 and a more pronounced IL-8 secretion than healthy or AP HGF. We also tested the ability of human serum antibodies against Aa to moderate the Aa-elicited HGF cytokine secretion by adding human serum, with normal or elevated antibody content. Both sera appeared to have an upregulating effect on IL-6 and IL-8 secretion. Depletion of 95% of the anti-Aa antibody from serum by absorption did not affect its activity. Based on the response of HGF from two LJP patients, we propose that Aa-induced pathology in LJP may be modulated by stimulation of rapid and/or exaggerated secretion of cytokines with potential catabolic effects, although studies with a larger group of LJP patients are needed to further test this hypothesis. Furthermore, serum antibodies against this microorganism do not appear to have a neutralizing effect in cytokine-eliciting HGF-Aa interactions.
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PMID:Gingival fibroblast cytokine profiles in Actinobacillus actinomycetemcomitans-associated periodontitis. 888 44

Treatment with the tetracycline HCL-containing (Actisite infinity) fiber has been shown to improve clinical measures of periodontitis, as well as reduce the number of sites infected with putative periodontal pathogens. In this study, we examined the effect of the tetracycline fiber on biochemical mediators of the host's inflammatory response in gingival crevicular fluid (GCF). The total amount of the lysosomal enzyme beta-glucuronidase (beta G), considered a marker of primary granule release from polymorphonuclear leukocytes and interleukin-1 beta, a cytokine with important proinflammatory effects, were examined in GCF. Patients with localized recurrent periodontitis were followed over a 16 week period. Treated teeth (Tx), teeth adjacent to treated teeth (ADJ) and control teeth (Cx) were studied. Following fiber therapy, the Tx teeth displayed statistically significant reductions in mean probing depth, depth of the deepest site and bleeding on probing over the 16 weeks of the trial. Significant reduction in the depth of the deepest site was also seen for the ADJ teeth over 16 weeks. Total beta G in GCF was reduced for the Tx teeth comparing baseline to 16 weeks, but no significant changes were observed for the ADJ or Cx teeth. Prior to treatment, total beta G for the Tx teeth was 211 +/- 49 U (mean +/- standard error), versus 146 +/- 174 U for the ADJ teeth and 121 +/- 33 U for the Cx teeth. 16 weeks treatment, the mean values for these 3 categories of teeth were comparable (Tx = 95 +/- 20 U, ADJ = 93 +/- 42 U and Cx = 103 +/- 29 U). For the Tx teeth, the maximum reduction in total beta G following therapy occurred at 6 weeks (65%). Total IL-1 beta was significantly reduced for the Tx teeth at 3 and 6 weeks, but rebounded at 16 weeks. In contrast to what was seen for beta G, the maximum reduction in total IL-1 beta for the Tx teeth was observed at 3 weeks (68%). These data suggest that host mediators associated with increased risk for active disease are reduced following tetracycline fiber therapy. Future studies will determine the relative importance of a reduced microbial challenge versus a tetracycline-mediated direct modification of the host response to account for the reduction in the host inflammatory response in GCF following tetracycline fiber therapy.
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PMID:The effect of tetracycline fiber therapy on beta-glucuronidase and interleukin-1 beta in crevicular fluid. 889 31

Ketoprofen creams were evaluated for the treatment of periodontal disease in a placebo-controlled, double-blind study in the rhesus monkeys, Macaca mulatta. Two formulations containing ketoprofen (1%), with or without vitamin E, were evaluated against appropriate controls (8 monkeys per group). Two weeks prior to treatment, the animals received prophylaxis on only the left side of the mouth (spontaneous model). Selected teeth on the right side of the mouth were ligated (ligature model). The creams were administered to the gingiva once daily at a standard dose of 1.8 ml per monkey for 6 months. Clinical assessments were made 2 wk before initiation, at baseline and 1, 2, 3 and 6 months post-treatment. The clinical parameters included plaque formation, gingival redness, edema, bleeding on probing and Ramfjord Attachment Level measurements (RAL). Radiographs were taken at 2 wk before initiation, baseline and at 3 and 6 months post-treatment. Digital, subtraction radiography was used to measure vertical linear bone loss along the interproximal root surfaces of the left and right mandibular first molars. Gingival crevicular fluid (GCF) was collected for biochemical assays on PGE2, TxB2, LTB4, IL-1 beta and TNF alpha. There were no significant differences among groups with respect to gingival indices. Radiographic data demonstrated significant positive effects on bone activity in both groups treated with ketoprofen formulations with improvement over time in the ligature model (0.01 < or = p < or = 0.04). The placebo group exhibited bone loss of 1.96 +/- 0.48 and 1.40 +/- 0.56 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream showed an apparent bone gain of 0.28 +/- 0.41 and 0.78 +/- 0.47 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream containing vitamin E showed a mean bone loss of 0.41-0.48 mm per site at 3 months with improvement to an apparent bone gain of 0.31 +/- 0.44 mm per site at 6 months. The biochemical data demonstrated early and significant suppression of GCF-LTB4 by both ketoprofen formulations at 1 month, which preceded the significant suppression of GCF-PGE2 at 2 and 3 months in the ligature model (p < 0.003) and at 2 to 6 months in the spontaneous model (p < 0.02). We conclude that ketoprofen at 1% level in suitable topical vehicles can effectively inhibit GCF-LTB4 and GCF-PGE2 and positively alter alveolar bone activity in the ligature-induced model of periodontitis in the monkey.
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PMID:The effect of ketoprofen creams on periodontal disease in rhesus monkeys. 897 50

Although specific bacteria, dental plaque, and age are associated with periodontal disease, there are currently no reliable predictors of periodontitis severity. Studies in twins have suggested a genetic contribution to the pathogenesis of periodontitis, but previous attempts to identify genetic markers have been unsuccessful. The pro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) are key regulators of the host responses to microbial infection. IL-1 is also a major modulator of extracellular matrix catabolism and bone resorption. We report a specific genotype of the polymorphic IL-1 gene cluster that was associated with severity of periodontitis in non-smokers, and distinguished individuals with severe periodontitis from those with mild disease (odds ratio 18.9 for ages 40-60 years). Functionally, the specific periodontitis-associated IL-1 genotype comprises a variant in the IL-1B gene that is associated with high levels of IL-1 production. In smokers severe disease was not correlated with genotype. In this study, 86.0% of the severe periodontitis patients were accounted for by either smoking or the IL-1 genotype. This study demonstrates that specific genetic markers, that have been associated with increased IL-1 production, are a strong indicator of susceptibility to severe periodontitis in adults.
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PMID:The interleukin-1 genotype as a severity factor in adult periodontal disease. 904 1

The gingival crevicular fluid (GCF) and monocytic secretion of prostaglandin E2 (PGE2) and interleukin 1 beta (IL-1 beta) were measured in a group of 39 insulin-dependent diabetes mellitus (IDDM) patients and 64 systemically healthy individuals. Diabetics were divided into Group A (gingivitis or mild periodontal disease) and Group B (moderate or severe periodontal disease). Diabetics had significantly higher GCF levels of both PGE2 and IL-1 beta as compared to non-diabetic controls who were matched with regard to periodontal disease severity (P < 0.00001 and P = 0.0005, respectively). Within the diabetic population, the GCF levels of these inflammatory mediators were almost 2-fold higher in Group B as compared to Group A (P = 0.01, P = 0.006, respectively for GCF-PGE2 and IL-1 beta). Furthermore, diabetics as a group had a significantly higher monocytic PGE2 and IL-1 beta production in response to various concentrations of both Escherichia coli and Prophyromonas gingivalis lipopolysaccharide (LPS) as compared to non-diabetic patients with adult periodontitis (P = 0.0001). LPS dose-response curves demonstrated that monocytes from Group B diabetics produced approximately 3 times more PGE2 than Group A monocytes; however, there was no significant difference in monocytic IL-1 beta secretion within the IDDM patients. The levels of GCF or monocytic mediators did not correlate with age, race, or glycosylated hemoglobin (HbA1C) levels. Our data suggest that the high GCF and monocytic secretion of PGE2 and IL-1 beta in IDDM patients may be a consequence of a systemic response trait and that the presence of Gram-negative infections such as periodontal diseases may interact synergistically to yield high local levels of these mediators and a more severe periodontal condition.
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PMID:Inflammatory mediator response as a potential risk marker for periodontal diseases in insulin-dependent diabetes mellitus patients. 905 29

Chronic adult periodontitis is usually characterized by inflammatory cell accumulation in the extravascular periodontal connective tissue. In order to reveal how the lymphocyte migration and retention in periodontal lesions is regulated, we have focused on the molecular basis for the adhesive interactions between lymphocytes and human gingival fibroblasts (HGF). In this study, we investigated the involvement of cell adhesion molecules in adhesive interactions between lymphocytes and HGF. We found that activated lymphocytes bound strongly to HGF and VLA integrins, extracellular matrix receptors, play crucial roles in the binding. Interestingly, we first revealed that CD44 molecules (hyaluronate receptor) on lymphocytes also participated in lymphocyte-HGF interactions and that hyaluronate anchored on the surface of HGF functioned as the ligand for CD44. In addition, when HGF were stimulated with inflammatory cytokines such as IL-1, TNF alpha and IFN gamma, the binding avidity between lymphocytes and HGF was significantly increased and the adhesion was mainly mediated by LFA-1/ICAM-1 pathway. We then examined the possibility whether lymphocyte-HGF interaction may cause activation of HGF. When HGF directly interacted with lymphocytes for 3 h, IL-1 beta mRNA expression was clearly increased in HGF. These findings suggested that the adhesive interactions between lymphocytes and HGF was mediated at least by VLA integrins, LFA-1/ICAM-1 and CD44/hyaluronate and that the heterotypic cell-cell interactions could mutually cause intracellular signal transduction.
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PMID:Immunoregulatory roles of adhesive interactions between lymphocytes and gingival fibroblasts. 908 19


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