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)

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.
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PMID:Involvement of the kinin-forming system in the physiopathology of rheumatoid inflammation. 133 58

Excessive release of kinin (BK) in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 kinin receptors. Activation of the kinin forming system could be mediated 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-cytokine and cytokine mediators of inflammation, e.g., 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, vessel proliferation, inflammatory cell migration and, possibly, angiogenesis in pannus formation. These pathological changes, however, are not yet defined in the human model of chronic inflammation. The role of kinins and their interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes, such as rheumatoid arthritis, periodontitis, inflammatory diseases of the gut and osteomyelitis. Future development of specific potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as a pharmacological basis for more effective treatment of joint inflammatory and related diseases.
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PMID:Pathogenic responses of bradykinin system in chronic inflammatory rheumatoid disease. 770 72

Periodontitis is a chronic inflammatory disease of the soft and hard supporting tissues of the teeth and is a major cause of tooth loss in adults. The local host response to periodontopathic bacteria results in the release of inflammatory mediators and cytokines. Since cytokines are indicative of effector functions, we compared the pattern of cytokine production in periodontal patients and healthy controls. Specifically, we investigated the simultaneous presence of cytokines produced by T helper (Th)1, Th 2, and inflammatory cells which could be involved in periodontitis. We also compared the expression of these cytokine mRNAs in healthy and diseased tissues. No significant differences were detected at the protein or mRNA levels of the cytokines in the systemic circulation of patients and controls. The surface markers CD16 and CD56 were expressed on significantly fewer peripheral mononuclear cells of patients when compared to controls. gamma delta + T cells were found in half of the diseased tissues, but in none of the healthy tissues of either patients or controls. Finally, significant differences were observed between healthy and inflamed gingival tissues in the cytokine mRNA profile. Expression of IL-6 and IFN-alpha mRNA was significantly higher in diseased tissues compared to healthy tissues in patients.
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PMID:Detection of local and systemic cytokines in adult periodontitis. 872 10

Cytokines play an important role in the pathology associated with chronic inflammatory diseases. We measured the total amounts [picograms (pg)] and concentrations.(pg/microliter) of interleukin-1 alpha (IL-1 alpha), interleukin-8 (IL-8) and interferon-alpha (IFN-alpha) in 20 s gingival crevicular fluid (GCF) samples obtained from 2 diseased and 2 healthy sites in 20 subjects with periodontitis, and from 2 healthy sites in 20 subjects without disease. Both the mean amount and concentration of IL-1 alpha were significantly higher (p < 0.001) in diseased sites compared to healthy sites in subjects with disease. The results for IL-8 and IFN-alpha differed depending on the method of reporting. Whereas the amount of IL-8 was significantly higher (p < 0.01) in diseased sites, the mean concentration of IL-8 was lower compared to healthy sites. The mean amount of IFN-alpha was similar in health and disease; however, the concentration of IFN-alpha was significantly lower in diseased sites (p < 0.001) corresponding to the significant increase in crevicular fluid volume (p < 0.001). There were no significant differences in the amount or concentrations of the 3 cytokines between healthy sites from subjects with disease and healthy sites from healthy controls. The total amounts of both IFN-alpha and IL-8 were correlated between healthy and diseased sites in subjects. These data suggest that, while the disease status of a site is the major determinant of the levels of these cytokines locally, subjects with high levels of IL-8 and IFN-alpha in healthy sites also tend to have high levels of these cytokines in diseased sites. Finally, both the concentrations and total amounts of IL-8 and IFN-alpha were significantly correlated in diseased sites, suggesting that levels of these two cytokines rise or fall in tandem. The combination of decreased IL-8 and decreased IFN-alpha concentrations at diseased sites may reflect the reduced anti-bacterial host defense activity at that site.
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PMID:Interleukin-1 alpha, interleukin-8 and interferon-alpha levels in gingival crevicular fluid. 891 52

Chronic inflammatory reactions are usually characterized by inflammatory cell accumulation in the extravascular connective tissue. In such sites, inappropriate activation of circulating or resident lymphocytes becomes self-perpetuating and can lead to chronic tissue destruction. In addition to that, the locally infiltrated lymphocytes should have an opportunity to interact directly with fibroblasts composing the connective tissue. The direct interactions of those different cell types seem to play important roles in lymphocyte lodging and retention in such sites. Thus, for clarification of the immunopathogenesis of the chronic inflammatory diseases, including periodontitis, it is important that the molecular mechanisms involved in the heterotypic cell-cell interactions be revealed. In fact, it has been demonstrated that lymphocytes interact with various non-hematopoietic cells, such as epithelial cells and endothelial cells. Regarding interactions with fibroblasts, it has been shown that IFN gamma-stimulated fibroblasts can regulate the proliferative responses of T-lymphocytes both positively and negatively. Furthermore, activated lymphocytes have demonstrated strong binding ability to various fibroblast cell lines. Blocking experiments utilizing monoclonal antibodies specific to various cell adhesion molecules revealed that very late antigen (VLA) integrins, lymphocyte-function-associated antigen (LFA-1)/intercellular adhesion molecule-1 (ICAM-I), CD44/hyarulonate are, at least in part, involved in lymphocyte-fibroblast interactions. In addition, recent findings raised the possibility that the adhesive interactions between lymphocytes and fibroblasts influenced the various cellular functions of each cell type. In fact, it was recently demonstrated that the adhesive interactions stimulated fibroblasts to increase expression of inflammatory cytokine mRNA. These results strongly suggest that fibroblasts are not merely innocent bystanders but actively participate in local inflammatory reactions by directly interacting with locally infiltrated lymphocytes.
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PMID:Lymphocyte-fibroblast interactions. 906 24

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

The infiltration of leukocytes into inflammation sites such as observed in human periapical granulomas is considered to be mediated by chemotactic factors. In this study, we examined the presence of chemokine- and chemokine receptor-positive cells in samples obtained from human subjects by means of immunohistochemical methods. Macrophage chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and IFN-inducible protein 10 (IP-10)-producing cells were present in periapical granulomas. In addition, chemokine receptor CCR3-, CCR5-, and CXCR3-positive cells were also present. In contrast, no factor expression was observed in clinically healthy periodontal ligament, serving as a negative control. Our findings suggest that these chemokines are responsible for modulating the process of disease, such as human apical periodontitis.
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PMID:The presence of chemokine receptor (CCR5, CXCR3, CCR3)-positive cells and chemokine (MCP1, MIP-1alpha, MIP-1beta, IP-10)-positive cells in human periapical granulomas. 1168 86

Anti-neutrophil cytoplasmic Abs targeting proteinase 3 (PR3) have been detected in relation to a wide range of inflammatory conditions such as periodontitis, and interaction of anti-PR3 Abs with endothelial and epithelial cells provokes cell activation, although the underlying mechanism has been unclear. The present study showed that human oral epithelial cells expressed PR3 mRNA after treatment with proinflammatory cytokines such as IL-1alpha, TNF-alpha, IFN-alpha, IFN-beta, and IFN-gamma. A 29-kDa PR3 was expressed on the cell surface and released into culture supernatants by the cells upon stimulation with these cytokines. The membrane and supernatant fractions of oral epithelial cells exhibited enzymatic activity, which was inhibited by serine proteinase inhibitors, but not by a cysteine proteinase inhibitor or secretory leukocyte protease inhibitor. Addition of anti-PR3 Abs to cytokine-primed oral epithelial cells in culture induced remarkable secretion of IL-8 and monocyte chemoattractant protein 1 and aggregation of PR3 on the cells. RNA interference targeted to protease-activated receptor-2 mRNA and intracellular Ca2+ mobilization assays revealed that anti-PR3 Abs activated the epithelial cells through protease-activated receptor-2, a family of G protein-coupled receptors. The anti-PR3 Ab-mediated cell activation was completely abolished by RNA interference targeted to PR3 mRNA and by inhibition of phospholipase C and NF-kappaB. Immunohistochemistry showed that inflamed oral epithelium actually expresses PR3 protein. These results suggest that oral epithelial cells express functional PR3 in the inflamed sites and respond to anti-PR3 Abs detected in diseased sera, and that these mechanisms may actively participate in the inflammatory process, including periodontitis.
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PMID:Proinflammatory cytokines induce proteinase 3 as membrane-bound and secretory forms in human oral epithelial cells and antibodies to proteinase 3 activate the cells through protease-activated receptor-2. 2030 35

Inflammatory immune reactions in response to periodontopathogens trigger periodontal destruction, but their role to protect the host against infection remains unknown. Thus, we examined the mechanisms by which IFN-gamma modulates the outcome of Aggregatibacter actinomycetemcomitans-induced periodontal disease in mice. Our results showed that IFN-gamma deficient mice developed less severe periodontitis in response to A. actinomycetemcomitans infection, characterized by significant lower alveolar bone loss and inflammatory reaction. However, the absence of IFN-gamma results in increased bacterial load in periodontal tissues and higher acute phase reaction, followed by a disseminated bacterial infection and mice death during the course of the disease. Such impaired host response was found to be associated with a reduction in the levels of inflammatory cytokines and chemokines and in the number of GR1+, F4/80+, CD4+ and CD8+ leukocytes in the diseased periodontium of IFN-gamma deficient mice. In addition, the levels of both antimicrobial mediators myeloperoxidase and inducible nitric oxide synthase were also found to be reduced in IFN-KO mice. Our results demonstrate for the first time that a periodontal infection may be lethal in an immunocompromised host. In addition, the mechanisms involved in IFN-gamma mediated cell migration to diseased periodontal tissues, and its essential role to control A. actinomycetemcomitans infection were clarified.
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PMID:The essential role of IFN-gamma in the control of lethal Aggregatibacter actinomycetemcomitans infection in mice. 1840 43

Peripheral blood neutrophils from periodontitis patients exhibit a hyperreactive and hyperactive phenotype (collectively termed hyperresponsivity) in terms of production of reactive oxygen species (ROS). The molecular basis for this phenomenon, however, has yet to be determined. Our objectives were to identify genes differentially expressed in hyperresponsive peripheral blood neutrophils from chronic periodontitis patients relative to periodontally healthy controls and use these data to identify potential contributory pathways to the hyperresponsive neutrophil phenotype. Using microarray technology we demonstrated differential expression of 163 genes (149 increased, 14 decreased) representing a range of ontological classes. There was increased expression of a significant number of IFN-stimulated genes (ISG). RT-PCR analysis of ISG transcripts in individual and pooled samples further corroborated these data, and indicated that levels decreased to near those of controls following successful therapy. Significantly enhanced FcgammaR-stimulated ROS production was subsequently achieved by priming control neutrophils with IFN-alpha/-beta/-gamma, but not LPS, and gene expression analysis indicated that exposure to the type I IFN (in particular IFN-alpha) better replicated the mRNA profile observed in vivo. Further studies demonstrated that plasma levels of IFN-alpha were significantly higher in samples from patients relative to unaffected controls. Following successful periodontitis treatment, plasma IFN-alpha levels, neutrophil ISG expression, and FcgammaR-stimulated neutrophil ROS output of patients, all decreased to levels comparable with those of controls. In conclusion, although chronic periodontitis is a complex disease, raised IFN-alpha may be one determinant of the distinct molecular phenotype and hyperresponsivity exhibited by patients' peripheral blood neutrophils.
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PMID:Periodontitis associates with a type 1 IFN signature in peripheral blood neutrophils. 1883 37


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