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

The role of bacteria in the initiation of periodontitis is well-documented and the end result, destruction of the alveolar bone and periodontal connective tissue, is readily observed; but the events occurring between these two points in time remain obscure and are the focus of this paper. Bacteria induce tissue destruction indirectly by activating host defense cells, which in turn produce and release mediators that stimulate the effectors of connective tissue breakdown. Components of microbial plaque have the capacity to induce the initial infiltrate of inflammatory cells including lymphocytes, macrophages, and PMNs. Microbial components, especially lipopolysaccharide (LPS), have the capacity to activate macrophages to synthesize and secrete a wide array of molecules including the cytokines interleukin-1 (IL-1) and tumor-necrosis factor-alpha (TNF-alpha), prostaglandins, especially PGE2, and hydrolytic enzymes. Likewise, bacterial substances activate T lymphocytes and they produce IL-1 and lymphotoxin (LT), a molecule having properties very similar to TNF-alpha. These cytokines manifest potent proinflammatory and catabolic activities, and play key roles in periodontal tissue breakdown. They induce fibroblasts and macrophages to produce neutral metalloproteinases such as procollagenase and prostromelysin, the serine proteinase urokinase-type plasminogen activator (u-PA), tissue inhibitor of metalloproteinase (TIMP), and prostaglandins, u-PA converts plasminogen into plasmin, which can activate neutral metalloproteinase proenzymes, and these enzymes degrade the extracellular matrix components. TIMP inactivates the active enzymes and thereby blocks further tissue degradation. Several amplification and suppression mechanisms are involved in the process. While LPS activates macrophages to produce IL-1, IL-1 is autostimulatory and can therefore amplify and perpetuate its own production. Interferon-gamma (INF-gamma) suppresses autostimulation, but it enhances LPS-induced IL-1 production. PGE2 exerts a control over the whole process by suppressing production of both IL-1 and TNF-alpha. Furthermore, the activated cells produce an IL-1 receptor antagonist that binds to the IL-1 receptor but does not induce the biologic consequences of IL-1 binding. Other cytokines such as transforming growth factor-beta (TGF-beta) suppress production of metalloproteinases and u-PA. Thus the progression and extent of tissue degradation is likely to be determined in major part by relative concentrations and half-life of IL-1, TNF-alpha, and related cytokines, competing molecules such as the IL-1 receptor antagonist, and suppressive molecules such as TGF-beta and PGE2. These molecules control levels of latent and active metalloproteinase and u-PA, and the availability and concentration of TIMP determines the extent and duration of degradative activity.
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PMID:The role of inflammatory mediators in the pathogenesis of periodontal disease. 167 30

Inflammation-induced localized bone resorption in diseases such as marginal and apical periodontitis, rheumatoid arthritis, and osteomyelitis is due to activation and recruitment of osteoclasts by locally produced cytokines and inflammatory mediators. Thus several interleukins (1, 3, 4, 6, and 11), tumor necrosis factors (alpha, beta), colony-stimulating factors (M and GM), leukemia inhibitory factor, gamma-interferon, and transforming growth factor-beta have effects on bone resorption and bone formation in vivo and in vitro. The kallikrein-kinin system and the coagulation cascade are also activated in inflammation. We have found that peptides produced in the kallikrein-kinin system (bradykinin, kallidin) and thrombin, the end product in the coagulation cascade, can stimulate bone resorption in vitro. The stimulatory effect of bradykinin is linked both to B1 and B2 bradykinin receptors. Both kinins and thrombin stimulate prostaglandin biosynthesis in bone parallel with the bone resorptive effect. The stimulatory effect of bradykinin on bone resorption is completely lost when the prostaglandin response is abolished, whereas thrombin can stimulate bone resorption both via prostaglandin-dependent and independent mechanisms. In addition, bradykinin and thrombin act in concert with interleukin-1 to synergistically stimulate bone resorption and prostaglandin biosynthesis. We also have found that one of the acute-phase reactants, haptoglobin, can stimulate bone resorption in vitro, indicating the possibility of generalized bone loss in chronic inflammatory diseases. Moreover, haptoglobin synergistically potentiates bradykinin-induced and thrombin-induced prostanoid biosynthesis in osteoblasts. These observations indicate that the rate of bone resorption in inflammation-induced bone loss may not be due to a single factor but to the concerted action of several local or systemic factors.
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PMID:Regulation of bone metabolism by the kallikrein-kinin system, the coagulation cascade, and the acute-phase reactants. 752 72

Monocytes have recently been recognized as a precursor of Langerhans cells. This study examined the regulatory influence of the epithelial environment on the putative first step of the transition towards a Langerhans cell phenotype--the induction of CD1a antigen. The keratinocyte-derived cytokines granulocyte-macrophage-colony-stimulating factor, tumour necrosis factor-alpha, interleukin-6, and interleukin-1 beta induced CD1a expression, as did supernatants of keratinocytes extracted from inflammatory sites (periodontitis). Induction was abrogated by transforming growth factor-beta and a keratinocyte-derived interleukin-1 inhibitor. The optimal temperature for induction was 34 degrees C, not 37 degrees C. These results demonstrate that the components of the epithelial environment (cytokines and lower temperature) exert important influences, which may be part of local regulation of Langerhans cell development.
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PMID:Induction of the CD1a Langerhans cell marker on human monocytes. 754 Aug 33

Gingival mononuclear cell production of interleukin 1 (IL-1), interleukin 6 (IL-6) and transforming growth factor-beta (TGF-beta) after stimulation with the putative periodontopathic bacteria, Porphyromonas gingivalis and Fusobacterium nucleatum was investigated. Using an ELISA method, gingival mononuclear cells extracted from 18 adult periodontitis subjects were found to be producing IL-1. However, IL-1 activity could only be detected in 5 out of these 18 cases when tested using a thymocyte proliferation bio-assay, suggesting the presence of IL-1 inhibitors. Depletion of monocytes from peripheral blood cultures resulted in a significant decrease in IL-1 activity following P. gingivalis stimulation while there was no effect in the level of IL-1 activity following stimulation with F. nucleatum. This suggests that P. gingivalis and F. nucleatum stimulate different cell types to produce IL-1. Like IL-1, IL-6 production by gingival mononuclear cells was significantly greater than that produced by the control peripheral blood mononuclear cells. Following P. gingivalis and F. nucleatum stimulation, higher levels of IL-6 could be detected; however, both organisms stimulated similar levels. Intracytoplasmic immunofluorescence staining demonstrated a lower percent TGF-beta+ cells in bacterial stimulated peripheral blood mononuclear cell cultures compared with cells in medium alone. In the gingival mononuclear cell cultures, the percentage TGF-beta+ cells peaked at day 1 in F. nucleatum-stimulated, whereas in P. gingivalis-stimulated cultures the peak TGF-beta+ cells occurred at day 3, again suggesting stimulation of different cell subsets. These results illustrate that different periodontopathic bacteria may stimulate different cell types to produce cytokines which may have synergistic or antagonistic effects.
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PMID:Interleukin 1, interleukin 6 and transforming growth factor-beta production by human gingival mononuclear cells following stimulation with Porphyromonas gingivalis and Fusobacterium nucleatum. 838 62

Periodontitis is a chronic inflammatory disease characterized by a progression that is very much dependent on host response. The gingiva can be considered to be in a constant state of wounding (pathologic wounding by bacterial plaque) and a constant state of maintenance/repair. In this context, any metabolic disturbance in the host which compromises tissue repair/wound healing will exacerbate the progression of periodontitis. Diabetes presents an interesting example because two major complications of diabetes are delayed wound healing and periodontitis. Our previous studies indicate that delayed wound healing and periodontitis may be manifestations of a general systemic deficit in diabetes involving alteration of macrophage cytokine gene expression. The present study was designed to determine whether: 1) diabetes-induced metabolic alterations affect gingival cytokine levels; and 2) diabetes-induced metabolic alterations modify the gingival cytokine profile in periodontitis. Sprague-Dawley rats (N=12/group) were injected with streptozotocin (65 mg/kg) into the tail vein to induce diabetes (defined by blood glucose levels > 250 mg/dl) or received the injection vehicle or no treatment as controls. Periodontitis was induced in additional groups of diabetic and control rats by gavage with Porphyromonas gingivalis A7436. After 90 days, serum glucose was analyzed to document diabetes; alveolar bone level was measured to document severity of periodontitis; gingiva was harvested circumferentially from the first and second molars; and cytokines in gingival homogenates were assayed by ELISA using commercial kits. Cytokine levels were expressed as mean+/-SEM pg/microg protein. Diabetes alone did not alter the gingival cytokine profile for platelet-derived growth factor B (PDGF-B), interleukin 1-beta (IL-1beta), transforming growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha). Periodontitis alone demonstrated a significant increase (P < 0.05) in levels of PDGF-B and IL-1beta. Diabetes superimposed on periodontitis prevented these increases. Thus, diabetes-induced metabolic alterations do not affect gingival cytokine levels per se; however, they do alter the normal host response to periodontitis through blockage of periodontitis-induced increases in PDGF-B and IL-1beta.
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PMID:Diabetes prevents periodontitis-induced increases in gingival platelet derived growth factor-B and interleukin 1-beta in a rat model. 952 9

Increased proliferation of mucosal epithelium during inflammation is associated with degradation of subepithelial connective tissue matrix and local invasion of the epithelial cells. Here we have studied, whether collagenase-3 (MMP-13), a collagenolytic matrix metalloproteinase with an exceptionally wide substrate specificity, is expressed in the epithelium of chronically inflamed mucosa. Examination of human gingival tissue sections from subjects with chronic adult periodontitis with in situ hybridization revealed marked expression of MMP-13 in basal cells of some epithelial rete ridges expanding into connective tissue. Immunohistochemical staining demonstrated that these cells also expressed strongly laminin-5, suggesting that they are actively migrating cells. A strong signal for MMP-13 mRNA was occasionally also noted in the suprabasal epithelial cells facing the gingival pocket, whereas no collagenase-1 (MMP-1) mRNA was detected in any areas of the epithelium. MMP-13 expression was also detected in fibroblast-like cells associated with collagen fibers of the inflamed subepithelial connective tissue. In organ culture of human oral mucosa, MMP-13 mRNA expression was observed in epithelial cells growing into connective tissue of the specimens. Regulation of MMP-13 expression was examined in cultured normal nonkeratinizing epithelial cells isolated from porcine periodontal ligament. In these cells, MMP-13 expression at the mRNA and protein level was potently enhanced (up to sixfold) by tumor necrosis factor-alpha, transforming growth factor-beta(1), and transforming growth factor-alpha and by keratinocyte growth factor in the presence of heparin. In addition, plating periodontal ligament epithelial cells on type I collagen stimulated MMP-13 expression (sevenfold) as compared with cells grown on tissue culture plastic. The results of this study show, that expression of MMP-13 is specifically induced in undifferentiated epithelial cells during chronic inflammation due to exposure to cytokines and collagen. Thus, it is likely that MMP-13 expression is instrumental in the subepithelial collagenolysis and local invasion of the activated mucosal epithelium into the connective tissue.
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PMID:Collagenase-3 (matrix metalloproteinase-13) expression is induced in oral mucosal epithelium during chronic inflammation. 962 53

Soluble proteins that serve as mediators of cell function and are produced by various cell types, such as structural and inflammatory cells, are collectively called cytokines. Several lines of evidence have revealed that cytokines play important roles not only in tissue homeostasis but also in the pathogenesis of many infectious diseases. Recent research on biological activities in normal periodontium and the pathogenesis of periodontal diseases has clarified the involvement of various cytokines in the biological activities observed in the sites. Cytokines play crucial roles in the maintenance of tissue homeostasis, a process which requires a delicate balance between anabolic and catabolic activities. In particular, growth factors--such as fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), transforming growth factor-beta (TGF-beta)--are thought to play important roles in modulating the proliferation and/or migration of structural cells in the periodontium and the production of various extracellular matrices by these cells. On the other hand, there is little doubt that excessive and/or continuous production of cytokines in inflamed periodontal tissues is responsible for the progress of periodontitis and periodontal tissue destruction. Particularly, inflammatory cytokines--such as IL-1 alpha, IL-1 beta, IL-6, and IL-8--are present in the diseased periodontal tissues, and their unrestricted production seems to play a role in chronic leukocyte recruitment and tissue destruction. It is possible that monitoring cytokine production or its profile may allow us to diagnose an individual's periodontal disease status and/or susceptibility to the disease. In addition, although the hypothesis is still controversial, it has been suggested that discrete T-cell subsets (Th1 and Th2) with different cytokine profiles play specific roles in the immunopathogenesis of periodontal diseases.
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PMID:Cytokine expression in periodontal health and disease. 971 65

To characterize the T cell response to Porphyromonas gingivalis, we examined the expression of costimulatory molecules on T cells derived from adult periodontitis patients with high serum antibody titre to P. gingivalis. The expression of CD28, CTLA-4, CD40 ligand (CD40L) on CD4+ T cells was analysed by flow cytometry. IL-10 and transforming growth factor-beta (TGF-beta) mRNA expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and subsequent image analysis. Peripheral blood mononuclear cells (PBMC) derived from periodontitis patients showed higher proliferative responses to P. gingivalis outer membrane (OM) than those from healthy controls (P < 0.05). The percentage of CTLA-4+ cells within CD4+ T cells of patients was significantly higher than that of healthy controls after P. gingivalis OM stimulation (33.0% versus 11.9%, P < 0.01). There was no significant difference in the percentages of CD28+ cells and CD40L+ cells, and the percentage of CD40L+ cells was low in both groups even after stimulation. Stimulation of PBMC with P. gingivalis OM induced significantly higher IL-10 mRNA expression in periodontitis patients than in healthy controls (P < 0.05). The level of TGF-beta mRNA expression of patients tended to be higher than that of healthy controls, but there was no significant difference. To elucidate the functional role of CTLA-4, we further investigated the secondary proliferative response to P. gingivalis OM. Interestingly, P. gingivalis OM stimulation did not enhance antigen-specific secondary response. Anti-CTLA-4 MoAb had no effect on proliferation in the presence of P. gingivalis OM. CTLA-4Ig suppressed the proliferative response significantly (P < 0.01). These results suggest that T cell responses to P. gingivalis OM may be regulated by CTLA-4 that is expressed at the late phase of T cell activation, and, in part, immunosuppressive cytokines. Taken together, CTLA-4 may play a crucial role in the pathogenesis of chronic inflammatory periodontal disease.
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PMID:Elevated CTLA-4 expression on CD4 T cells from periodontitis patients stimulated with Porphyromonas gingivalis outer membrane antigen. 1063 63

'Bone: Formation by autoinduction', initiates by invocation of soluble molecular signals which, when combined to insoluble signals or substrata trigger the ripple-like cascade of bone differentiation by induction. The osteogenic proteins of the transforming growth factor-beta (TGF-beta) superfamily, the bone morphogenetic/osteogenic proteins (BMPs/OPs), and uniquely in the non-human primate Papio ursinus also the three mammalian TGF-beta isoforms, induce endochondral bone formation as recapitulation of embryonic development. The pleiotropic activities of the BMPs/OPs are vast and include the induction of periodontal tissue regeneration. Implantation of naturally derived highly purified osteogenic fractions after sequential adsorption/affinity and gel filtration chromatography in mandibular Class II furcation defects of P. ursinus induces cementogenesis as highly cellular collagenic cementoid attached to the exposed dentine with foci of nascent mineralization with inserted de novo generated Sharpey's fibres. Recombinant human osteogenic protein-1 (hOP-1) when implanted in Class II furcation defects of P. ursinus with surgically exposed dentine matrix preferentially initiates the induction of cementogenesis; on the other hand, hBMP-2 preferentially induces alveolar bone regeneration with mineralized bone covered by prominent osteoid seams. Long-term studies with gamma-irradiated 0.5 and 2.5mg hOP-1 per gram of xenogeneic bovine collagenous matrix induce the restitutio ad integrum of the periodontal tissues in furcation defects exposed by chronic periodontitis in P. ursinus. A challenging question for tissue engineering and regenerative medicine is whether the presence of molecularly different osteogenic proteins of the TGF-beta superfamily has a therapeutic significance. Mechanistically, the specificity of hOP-1 primarily initiating cementogenesis in periodontal defects is regulated by both the dentine extracellular matrix upon which responding cells attach and differentiate, and the structure/activity profile of the implanted hOP-1; the limited induction of cementogenesis by hBMP-2 in furcation defects of non-human primate and canine models is consistent with the reported data that hBMP-2 inhibits differentiation and mineralization of cementoblasts in vitro aside the specific structure/activity profile of the implanted hBMP-2 protein. The induction of periodontal tissue regeneration develops as a mosaic structure in which the osteogenic proteins of the TGF-beta superfamily singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis as a recapitulation of embryonic development.
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PMID:Bone morphogenetic proteins, cementogenesis, myoblastic stem cells and the induction of periodontal tissue regeneration. 1989 1

Porphyromonas gingivalis has been associated with subgingival biofilms in adult periodontitis. However, the molecular mechanisms of its contribution to chronic gingival inflammation and loss of periodontal structural integrity remain unclear. This investigation aimed to examine changes in the host transcriptional profiles during a P. gingivalis infection using a murine calvarial model of inflammation and bone resorption. P. gingivalis FDC 381 was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated from infected soft tissues and calvarial bones and was analysed for transcript profiles using Murine GeneChip((R)) arrays to provide a molecular profile of the events that occur following infection of these tissues. After P. gingivalis infection, 6452 and 2341 probe sets in the infected soft tissues and calvarial bone, respectively, were differentially expressed (P </= 0.05). Biological pathways significantly impacted by P. gingivalis infection in tissues and calvarial bone included cell adhesion (immune system) molecules, Toll-like receptors, B-cell receptor signaling, transforming growth factor-beta cytokine family receptor signaling, and major histocompatibility complex class II antigen processing pathways resulting in proinflammatory, chemotactic effects, T-cell stimulation, and downregulation of antiviral and T-cell chemotactic effects. P. gingivalis-induced inflammation activated osteoclasts, leading to local bone resorption. This is the first in vivo evidence that localized P. gingivalis infection differentially induces transcription of a broad array of host genes, the profiles of which differed between inflamed soft tissues and calvarial bone.
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PMID:Porphyromonas gingivalis infection-induced tissue and bone transcriptional profiles. 2033 94


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