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)

Kinins are potent mediators of rheumatoid inflammation. The components of the kinin-forming system are hyperactive in RA. Excessive release of kinins in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 receptors. These receptors could be stimulated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokines and cytokines mediators of inflammation, for example, PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessels proliferation, inflammatory cells migration, and possibly angiogenesis in pannus formation. These pathological changes, however, are not yet defined in human model of chronic inflammation (RA). Hence, the role of kinin and its interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory joint diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes (RA, periodontitis and osteomyelitis), and they represent and important area for continued research in rheumatology. Future development of specific, potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as pharmacological basis of more effective rationally-based therapies for RA. This may lead to significant advances in our knowledge of the mechanisms and therapeutics of rheumatic diseases.
 ...
PMID:Involvement of the kinin-forming system in the physiopathology of rheumatoid inflammation. 133 58

Interleukin-1(IL-1), a cytokine present in the gingiva and crevicular fluid of patients with periodontitis and in the periodontal ligament (PDL) of experimentally moved teeth, has multiple biological activities, including the ability to elicit bone resorption. Interleukin-6, also found in the gingiva of patients with periodontitis, may induce osteoclastic bone resorption through an effect on osteoclastogenesis. Here IL-6 production and its gene expression in response to recombinant IL-1 beta were examined in primary cultures of PDL cells. IL-1 beta stimulated IL-6 production by these cells in a dose- and time-dependent manner; this increase in IL-6 production was much higher than that in human gingival fibroblasts. In situ hybridization, using a synthetic oligonucleotide DNA probe of the IL-6 gene, revealed that most PDL cells expressed IL-6 mRNA in response to IL-1 beta treatment. The finding that IL-6 is produced by PDL cells and is regulated by IL-1 beta has revealed a potentially important mechanism for controlling alveolar bone resorption.
 ...
PMID:Stimulation by interleukin-1 of interleukin-6 production by human periodontal ligament cells. 141 23

We have estimated the levels of Interleukin-1 beta (IL-1 beta) by ELISA in gingival crevicular fluid (GCF) at 58 sites from 37 patients with adult periodontitis. GCF was collected for 5 s on filter papers and a 2nd sample was collected for 30 s 1 min later. 68/116 strips yielded detectable levels of IL-1 beta. IL-1 beta was present in both the 1st and 2nd samples at 28 sites, in the 1st only at 4 sites and in the 2nd only at 8 sites; 18 sites were below the level of detection for the assay. When the concentrations of IL-1 beta were calculated in the original volume of GCF on each strip, the mean value for positive strips was 34.16 +/- 29.45 (SD) pg/microliters with a range from 1.75 to 97.13 pg/microliters. There were no statistically significant correlations with the plaque index, bleeding index or probable crevice depth (pocket depth). The results indicate that IL-1 is present in the GCF from a proportion of sites with evidence of previous periodontal destruction.
 ...
PMID:Interleukin-1 beta (IL-1 beta) levels in gingival crevicular fluid from adults with previous evidence of destructive periodontitis. A cross sectional study. 173 10

Samples of gingival crevicular fluid (GCF) were harvested from sites manifesting features characteristic of active disease including inflammation, periodontal attachment loss, and radiographic signs of alveolar bone destruction in untreated patients with advanced periodontitis. The presence and concentrations of interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) were measured using ELISAs specific for these cytokine molecules. IL-1 alpha and/or IL-1 beta were identified in the GCF of 15 of 15 patients having untreated periodontitis. Ninety percent (71 of 79) of the sites tested contained measureable amounts of IL-1, with IL-1 beta as the more frequently occurring form. IL-1 alpha levels ranged from 0.23 nM to 13.9 nM in the GCFs. IL-1 beta levels were between 0.04 nM and 5.28 nM. Marked reductions of total IL-1 levels were observed following effective treatment. Both forms of IL-1 messenger RNA (mRNA) were detected in 17 of 17 gingival tissue samples from 6 patients. These results demonstrate that IL-1 is produced and released locally in periodontal disease at concentrations sufficient to mediate tissue inflammation and bone resorption. IL-1 may serve as a marker of periodontal tissue destruction.
 ...
PMID:Measurement of interleukin-1 alpha and -1 beta in gingival crevicular fluid: implications for the pathogenesis of periodontal disease. 214 75

An in vitro model is used to investigate the hypothesis that activated fibroblasts produce collagenolytic activity in inflammatory sites. Interleukin-1, a cytokine present in the gingiva and crevicular fluid of periodontitis patients, has multiple biologic activities including the ability to stimulate collagenase in dermal and synovial fibroblasts. In this report IL-1 is tested on gingival (GF) and periodontal ligament fibroblasts (PLF) for its ability to increase collagenolytic activity and procollagenase mRNA and protein. GF produce a 3- to 7-fold increase in collagenase activity, while PLF collagenase activity is rarely increased above control amounts by IL-1 treatment. In contrast, both cell types demonstrate an increase in procollagenase protein production with IL-1 treatment. RNA from both GF and PLF contain procollagenase mRNA as demonstrated when northern blots of fibroblast total RNA are hybridized with the cDNA for human procollagenase. Treatment with IL-1 increases the steady-state levels of this message in GF by up to 10-fold in 48 hours when measured with dot blot analysis standardized for poly-A RNA. PLF also produce up to 7 times more message at the same dose and time. Since fibroblasts present in the lesion are exposed to inflammatory cell products it is possible that the production of collagenase by these cells could result in the destruction of the periodontal fibrous attachment.
 ...
PMID:Interleukin-1 regulation of procollagenase mRNA and protein in periodontal fibroblasts in vitro. 216 52

The evidence that periodontitis-associated bacteria contain potent PBA factors is very strong. Clearly, antibodies directed against non-oral antigens are produced in the inflamed periodontal lesion, and PBA appears to contribute to that production. It is also clear that B cells and plasma cells are the major cell types in the periodontal lesion. Furthermore, alterations in the regulation of B-cell responses to PBA factors are associated with severe periodontal disease. However, evidence demonstrating that activated B cells and plasma cells are directly involved in the pathogenic mechanisms leading to destruction of the periodontal support is still circumstantial. Polyclonal B-cell activation and potential pathways by which PBA-stimulated cells could be involved in periodontal destruction remain largely hypothetical. It appears that IL-1 is an important osteoclast-activating agent, and that LPS, which is a potent PBA factor in many systems, can elicit IL-1 production by B cells as well as by the monocyte/macrophage lineage. Recent data indicating that IL-1 is produced by numerous malignant B-cell lines lend support for the idea that B-cell IL-1 could be important in bone resorption. It is also likely that polyclonal activation may lead to production of autoantibody such as anti-type I and anti-type III collagens, and the destruction of self tissues through ADCC reactions, immune complex formation, and complement activation. Further research is needed to determine how the B cell/plasma cell may participate in tissue injury in periodontitis, and how the B-cell response to PBA factors is regulated.
 ...
PMID:Polyclonal B-cell activation in periodontitis. 252 22

The role of the polymorphonuclear leukocyte (PMNL) as a primary protective cell in periodontal diseases has been well recognized. Functional abnormalities of PMNL chemotaxis have been implicated in the pathogenesis of some types of periodontitis. However, no consistent correlation with other PMNL functions has been reported. In the present study, phagocytosis and intracellular killing (oxidative product formation) of the PMNL from the patients with various forms of periodontal disease were evaluated by flow cytometry. Moreover, interleukin 1 (IL-1) production by the PMNL was determined by means of the enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies against rIL-1 alpha and rIL-1 beta. In order to examine these functions of peripheral (p-PMNL) and/or gingival crevicular PMNL (g-PMNL), 15 patients with localized juvenile periodontitis (LJP), 13 patients with generalized juvenile periodontitis (GJP) and 52 patients with adult periodontitis (AP) served as subjects. About 50% of the patients in LJP and GJP group exhibited depressed p-PMNL phagocytosis. While only a minimal number of the AP patients and no healthy subjects showed any reduction of p-PMNL phagocytosis. The reduction of phagocytosis was not related to the clinical periodontal status, and no detectable improvement of p-PMNL phagocytosis could be observed after periodontal therapy. In addition, it was suggested that complement receptors on the p-PMNL might be closely related with the reduction. Compared to p-PMNL, g-PMNL from the same individual have a lower phagocytic capacity in all subjects. However, no significant difference in g-PMNL phagocytosis could be demonstrated among three patient groups. Incremental oxidative responses in p-PMNL were observed in LJP, GJP and AP patients without any significant difference being found among these three groups. The increased rate of oxidative product formation was related to the clinical periodontal status, and it followed that periodontal therapy had significant effect on the improvement of this p-PMNL function. In IL-1 production assay of PMNL, a significant amount of IL-1, especially IL-1 beta, was observed in g-PMNL, but not in p-PMNL. The g-PMNL of the patients was found to produce greater amounts of IL-1 alpha and IL-1 beta than did the healthy controls. In addition, IL-1 production of p-PMNL was induced by the stimulation with some pathogenic bacteria including Bacteroides gingivalis. These results suggest that impaired PMNL phagocytosis may contribute to the early onset of periodontal deterioration in some young patients.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Phagocytosis, intracellular killing and interleukin 1 production of polymorphonuclear leukocytes in human periodontal diseases]. 263 96

The biological activities of lipopolysaccharide from Bacteroides gingivalis 381 (B-LPS) were examined in vivo and in vitro. Intra-oral mucosal injection of B-LPS induced an acute inflammation at the injection site. Intravenous injection of B-LPS induced necrotic lesions with many thrombi in the liver and lymphocytic reduction in the spleen. By immunohistochemical examination, B-LPS was detected in macrophages in the liver, spleen and lymph nodes. In vitro analysis showed that B-LPS was a potent activator of both neutrophils and macrophages in luminol-dependent response and IL-1 secretion from macrophages and was mitogenic to the spleen cells not only from BALB/c mice but also from LPS-non-responder C3H/HeJ mice. Interferon production from human peripheral mononuclear leucocytes was induced, in vitro, by stimulation with B-LPS but not with the other enterobacterial LPS. These findings clarified the various biological activities of B-LPS affecting various cells and tissues, especially neutrophils, macrophages and lymphocytes. The potent inflammability of B-LPS shown in the present study indicates that it is one of the effective agents to induce periodontitis.
 ...
PMID:Histological changes and some in vitro biological activities induced by lipopolysaccharide from Bacteroides gingivalis. 314 May 33

Whole Gram-negative bacteria associated with juvenile and adult periodontitis, and their respective extracted lipopolysaccharides (LPS), were tested for the ability to activate quiescent human peripheral blood monocytes. All pathogenic Gram-negative bacteria and all LPS tested were able to induce the production of significant amounts of IL-1 and TNF, monokines known to induce osteoclastic bone resorption. Haemophilus segnis, which has not been associated with any form of periodontal disease, did not activate monocytes. Purified LPS from Actinobacillus actinomycetemcomitans Y4 was able to elicit IL-1 and TNF release at a threshold concentration of 1-10 ng/mL. To examine the mechanism whereby whole bacteria activated monocytes, we added polymixin B in culture with glutaraldehyde-fixed bacteria to bind LPS. This resulted in the abrogation of IL-1 and TNF production. To compare the effects of Gram-positive oral bacteria on monocytes, we also tested Staphylococcus epidermidis and the Gram-positive amphipathic equivalent of LPS, lipoteichoic acid (LTA) extracted from Staphylococcus aureus bacteria. Whereas whole Gram-positive bacteria had no stimulatory effect on monocytes, LTA induced IL-1 and TNF production at a concentration range equivalent to that of the LPS. These results indicate that monocytes are activated by free LPS or LPS bound to Gram-negative pathogenic periodontal bacteria to produce monokines which may contribute to the destruction of periodontal bone.
 ...
PMID:Production of interleukin-1 and tumor necrosis factor by human peripheral monocytes activated by periodontal bacteria and extracted lipopolysaccharides. 326 3

Endothelial cell activation by endotoxin (LPS), tumor necrosis factor (TNF), Interleukin-1-alpha, beta (IL-1-alpha, beta) and phorbolesters (TPA) results in increased monocyte adhesion. Examination of kinetics of monocyte adhesion shows that the onset of adherence enhancement (AE) is similar in all five agents (about 300% AE at 6 h), while its decrease is delayed in LPS/TNF versus IL-1-alpha, beta/TPA-induced activation (LPS versus IL-1-beta:260% versus 60% at 18 h). Monoclonal antibody (4D10), raised against 24 h LPS-stimulated endothelial cells detects an endothelial cell-specific activation antigen at Mr 81,000 that is induced by LPS, TNF, IL-1-alpha, beta and TPA (within 6 h about 100% positive cells). Decrease in antigen-positive cells is delayed in LPS/TNF versus IL-1-alpha, beta/TPA-induced antigen expression (LPS vs. IL-1-beta: 60% vs. 5% at 24 h). In situ the antigen is not expressed in normal and chronic inflammatory tissues. Acute inflammatory tissues, including contact and atopic dermatitis, psoriasis and periodontitis, however, show endothelial cells staining strongly positive. In contact eczemas at different times after elicitation (0, 6, 24, 72, 96 h), expression of the antigen is first seen after 24 h and is still strong at 96 h. These data indicate that LPS/TNF conduct an endothelial cell activation program in vitro, showing the same prolonged kinetics that is found for endothelial cell activation in the acute inflammatory process in vivo.
 ...
PMID:Characterization and expression kinetics of an endothelial cell activation antigen present in vivo only in acute inflammatory tissues. 331 46


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