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)

Ceramide has been proposed as a second messenger molecule implicated in a variety of biological processes, including apoptosis. Recently, it has been reported that tumor necrosis factor-alpha (TNF-alpha) activates the release of ceramide and that ceramide acts as a mediator for the TNF-alpha-induced stimulation of the binding affinity of nuclear factor-KB (NF-KB), a ubiquitous transcription factor of particular importance in immune and inflammatory responses. In this study we demonstrate that dexamethasone, which reduces the production of ceramide, significantly inhibits TNF-alpha-induced activation of NF-KB, c-Jun N-terminal kinase, also known as stress-activating protein kinase, caspase-3-like cysteine protease, redistribution of cytochrome c, and apoptosis in MC3T3E1 osteoblasts. Compared with TNF-alpha-induced JNK activation, ceramide elicits a more rapid activation of JNK within 30 min. C2-ceramide activates NF-KB and caspase-3 like protease to the same degree and with kinetics similar to those of TNF-alpha. This study provides evidence that the release of ceramide may be required as a second messenger in TNF-alpha-induced apoptosis. These results also suggest a regulatory role for dexamethasone in TNF-alpha-induced apoptosis via inhibition of ceramide release. Therefore, our in vitro results suggest that therapies targeted at the inhibition of ceramide release may abrogate inflammatory processes in TNF-alpha-related diseases, including rheumatoid arthritis and periodontitis.
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PMID:Dexamethasone suppresses tumor necrosis factor-alpha-induced apoptosis in osteoblasts: possible role for ceramide. 1091 78

Stimulated neutrophils from subjects with various inflammatory tissue-destructive conditions, such as periodontal, pulmonary, gastrointestinal, and cardiovascular diseases, generate more oxygen radicals and proteases, implicated in tissue destruction, than neutrophils from healthy persons. Cigarette smoking aggravates these diseases. The aim of our study was to investigate the effect of cigarette smoking on the priming capacity of tumor necrosis factor-alpha, measured as generation of radicals from stimulated neutrophils, in smoking and non-smoking subjects with or without periodontitis. The priming effect was higher in neutrophils from smokers. In the group with periodontitis, smoking caused an even greater increase in the generation of radicals, indicating an additive effect of this local disease. The membrane expression of CD11b, CD15, and CD63 was significantly higher on neutrophils from smokers, indicating upregulated neutrophil functions. This increased priming effect of tumor necrosis factor-alpha in smokers subjects could be of importance in the aggravation of tissue-destructive inflammatory diseases.
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PMID:Cigarette smoking as an aggravating factor in inflammatory tissue-destructive diseases. Increase in tumor necrosis Factor-alpha priming of peripheral neutrophils measured as generation of oxygen radicals. 1128 9

Proteases produced by Porphyromonas gingivalis, an oral pathogen, are considered important virulence factors and may affect the responses of cells equipped with proteinase-activated receptors. The aim of this study was to investigate the effect of the arginine-specific cysteine protease gingipain-R produced by P. gingivalis on chemokine production by human gingival fibroblasts (HGF) and the effect of gingipain-R treatment on the subsequent contact-dependent activation of HGF by T cells. HGF incubated in the presence of purified 47-kDa gingipain-R showed increased levels of interleukin-8 (IL-8) mRNA. Cyclooxygenase-2 (COX-2) mRNA was also induced. Further exposure of HGF to activated T cells resulted in the dose- and time-dependent enhancement of IL-8 transcription and release. T-cell membrane-bound tumor necrosis factor (TNF) was the ligand inducing IL-8 production by HGF, since TNF neutralization abrogated HGF responses to T-cell contact. The enhanced IL-8 release was due, at least in part, to prostaglandin-E(2) production, which was mostly blocked by indomethacin. Gingipain-R proteolytic activity was required since heat inactivation, specific synthetic protease inhibitors, and the natural substrate competitor histatin 5 abrogated its effects. The enhanced production of IL-8 in response to T-cell contact was specific since monocyte chemotactic protein-1 (MCP-1) production was unaffected while interferon-gamma-inducible protein-10 (IP-10) was inhibited. The sum of these activities may result in the recruitment of differential cell types to sites of inflammation since IL-8 preferentially recruits neutrophils and IP-10 attracts activated T cells and may be relevant to the pathogenesis of periodontitis.
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PMID:Porphyromonas gingivalis gingipain-R enhances interleukin-8 but decreases gamma interferon-inducible protein 10 production by human gingival fibroblasts in response to T-cell contact. 1140 91

In a previous study, we developed a specific monoclonal antibody against Porphyromonas endodontalis lipopolysaccharide, and demonstrated that this lipopolysaccharide was detected in bacterially infected root canal fluid. We suggest here that P. endodontalis lipopolysaccharide in the infectious materials plays a stimulatory role in maxillofacial abscess formation via the expression of inflammatory cytokines. Our epidemiological study showed that this lipopolysaccharide was detected in significant levels the infectious material of patients with periapical periodontitis and odontogenic abscesses. Interestingly, infectious material-induced expression of tumor necrosis factor-alpha, interleukin-1beta, or neutrophil chemoattractant KC genes in mouse macrophages, was significantly neutralized by monoclonal antibody against the lipopolysaccharide. In addition, we also detected a significant amount of tumor necrosis factor-alpha in the infectious material. These results suggest that P. endodontalis lipopolysaccharide plays an important role in the pathogenic mechanism of maxillofacial abscess formation via the expression of inflammatory cytokines.
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PMID:A possible mechanism of maxillofacial abscess formation: involvement of Porphyromonas endodontalis lipopolysaccharide via the expression of inflammatory cytokines. 1173 53

Diabetes mellitus is a systemic disease with several major complications affecting both the quality and length of life. One of these complications is periodontal disease (periodontitis). Periodontitis is much more than a localized oral infection. Recent data indicate that periodontitis may cause changes in systemic physiology. The interrelationships between periodontitis and diabetes provide an example of systemic disease predisposing to oral infection, and once that infection is established, the oral infection exacerbates systemic disease. In this case, it may also be possible for the oral infection to predispose to systemic disease. In order to understand the cellular/molecular mechanisms responsible for such a cyclical association, one must identify common physiological changes associated with diabetes and periodontitis that produce a synergy when the conditions coexist. A potential mechanistic link involves the broad axis of inflammation, specifically immune cell phenotype, serum lipid levels, and tissue homeostasis. Diabetes-induced changes in immune cell function produce an inflammatory immune cell phenotype (upregulation of proinflammatory cytokines from monocytes/polymorphonuclear leukocytes and downregulation of growth factors from macrophages). This predisposes to chronic inflammation, progressive tissue breakdown, and diminished tissue repair capacity. Periodontal tissues frequently manifest these changes because they are constantly wounded by substances emanating from bacterial biofilms. Diabetic patients are prone to elevated low density lipoprotein cholesterol and triglycerides (LDL/TRG) even when blood glucose levels are well controlled. This is significant, as recent studies demonstrate that hyperlipidemia may be one of the factors associated with diabetes-induced immune cell alterations. Recent human studies have established a relationship between high serum lipid levels and periodontitis. Some evidence now suggests that periodontitis itself may lead to elevated LDL/TRG. Periodontitis-induced bacteremia/endotoxemia has been shown to cause elevations of serum proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), which have been demonstrated to produce alterations in lipid metabolism leading to hyperlipidemia. Within this context, periodontitis may contribute to elevated proinflammatory cytokines/serum lipids and potentially to systemic disease arising from chronic hyperlipidemia and/or increased inflammatory mediators. These cytokines can produce an insulin resistance syndrome similar to that observed in diabetes and initiate destruction of pancreatic beta cells leading to development of diabetes. Thus, there is potential for periodontitis to exacerbate diabetes-induced hyperlipidemia, immune cell alterations, and diminished tissue repair capacity. It may also be possible for chronic periodontitis to induce diabetes.
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PMID:Periodontitis and diabetes interrelationships: role of inflammation. 1188 55

Evidence points to an increased cytokine response in type 2 diabetes, especially the proinflammatory cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha. Genetics, age, and, nutrition are important signals for this increased response and as reported more recently, infections and inflammation. Persistent elevation of IL-1 beta, IL-6, and TNF-alpha in the diabetic state have an effect on the liver, stimulate the release of acute-phase proteins, produce the characteristic dysregulation of lipid metabolism associated with type 2 diabetes, and have effects on pancreatic beta cells as well. In addition, TNF-alpha, a potent inhibitor of the tyrosine kinase activity of the insulin receptor, has been implicated as an etiologic factor for insulin resistance. Collectively, the evidence supports a role for cytokine elevation in the pathophysiology and metabolic abnormalities associated with diabetes. Periodontitis is an infection that is twice as prevalent in diabetic individuals compared to non-diabetics. Porphyromonas gingivalis, one of the microorganisms responsible for this infection, is able to invade endothelial cells and is a potent signal for monocyte and macrophage activation. Thus, once established in the diabetic host, this chronic infection complicates diabetes control and increases the occurrence and severity of microvascular and macrovascular complications. Unlike treatment of acute infections, modalities of treatment for chronic infections are a matter of debate. Evidence indicates that mechanical removal of subgingival infection does not result in complete elimination of periodontal infection and consequently there is no effect on diabetes control measured as reduction in glycated hemoglobin. On the other hand, studies incorporating systemic antibiotics as adjuncts to mechanical debridement result in a reduction of P. gingivalis to nondetectable levels and a concomitant reduction in glycated hemoglobin, independent of the hypoglycemic effects of diabetes drugs or insulin. The evidence supports the notion that treatment of chronic periodontal infection is essential in the diabetic patient. Assessment of infection status in diabetic patients is fundamental for appropriate treatment decisions.
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PMID:Treatment of periodontal disease and control of diabetes: an assessment of the evidence and need for future research. 1188 56

Epidemiological studies have implicated periodontitis (PD) as a risk factor for development of cardiovascular disease (CVD). Persistent infections such as periodontitis induce inflammatory and immune responses which may contribute to coronary atherogenesis, and, in conjunction with other risk factors, may lead to coronary heart disease (CHD). In this review, mechanisms are described that may help explain the association between periodontal infections and CHD. Periodontal diseases are bacterial infections associated with bacteremia, inflammation, and a strong immune response, all of which may represent significant risk factors for the development of atherogenesis, CHD, and myocardial infarction (MI). Several mechanisms may participate in this association, including those induced by oral organisms, and those associated with host response factors. This review will focus on host factors. Oral pathogens and inflammatory mediators (such as interleukin [IL]-1 and tumor necrosis factor [TNF]-alpha) from periodontal lesions intermittently reach the bloodstream inducing systemic inflammatory reactants such as acute-phase proteins, and immune effectors including systemic antibodies to periodontal bacteria. This review will describe the potential role of various inflammatory as well as immunologic factors that may play a role in periodontitis as a possible risk factor for CHD.
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PMID:The role of inflammatory and immunological mediators in periodontitis and cardiovascular disease. 1188 69

Periodontitis is a chronic inflammatory disease initiated by a multitude of bacteria. Persistent infection leads to generation of various inflammatory mediators, resulting in tissue destruction and osteoclastic resorption of the alveolar bone. This study describes a novel in vivo murine calvarial model to assess the effects of oral pathogens on the expression of three proinflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha] which are involved in bone resorption. We chose Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans as prototype oral pathogens. We also tested the effects of Streptococcus gordonii, an oral commensal supragingival microorganism, considered a non-pathogen. Live bacteria were injected into subcutaneous tissue overlying the parietal bone of mice calvaria for 6 days. At the end of the experimental period, tissues overlying the calvaria were removed and analyzed for proinflammatory cytokine expression by Northern blotting. Cytokine mRNA was not detected in the tissue over the calvaria of control animals. In contrast, P. gingivalis and A. actinomycetemcomitans elicited mRNA expression of all three cytokines, TNFalpha being the highest (TNFalpha > > IL-1beta > IL-6). P. gingivalis was more potent than A. actinomycetemcomitans in inducing cytokine expression. In contrast, S. gordonii induced only low levels of mRNA for IL-1beta and TNFalpha but no IL-6 mRNA induction. These results suggest that oral microorganisms with access to host tissues elicit a battery of proinflammatory cytokines. There were clear differences in profiles and, interestingly, a commensal bacterium also stimulated bone resorptive cytokine expression in host tissues.
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PMID:In vivo induction of proinflammatory cytokines in mouse tissue by Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. 1203 Sep 70

In recent years, studies have demonstrated an association between human cytomegalovirus (HCMV) and destructive periodontal disease. It has been shown that reactivation of HCMV in periodontitis lesions may be related to progressing periodontal disease. Several possible mechanisms by which HCMV exerts periodontopathic potential have been previously proposed. These are reviewed and include the upregulation of bone resorptive cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) by active HCMV infection at the periodontitis site. This review focuses on the molecular basis of IL-1beta gene activation by HCMV immediate early (IE) gene products. A novel hypothesis is also described whereby HCMV plays a significant role in the pathogenesis of periodontal disease by the ability of its IE proteins to strongly transactivate IL-1beta gene expression. More studies are needed to further explore this hypothesis and clarify the association between HCMV and periodontitis.
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PMID:Activation of interleukin 1beta gene transcription by human cytomegalovirus: molecular mechanisms and relevance to periodontitis. 1265 93

Periodontal disease is the result of a complex interplay of bacterial infection and host responses, and is often modified by various systemic diseases such as diabetes mellitus. Such diseases are capable of affecting the periodontium and/or the treatment of periodontal disease. However, recent research has changed our concept of how periodontal disease should be treated. Here we present several concerns directed towards the periodontal therapy of patients with diabetes mellitus based on our studies. When treating periodontitis patients who have diabetes mellitus it is important to consider the type of diabetes. Patients with non-insulin dependent diabetes mellitus can be further classified according to the degree of insulin resistance, since recent epidemiological studies have suggested that successful anti-microbial therapy might result in improved insulin resistance in highly insulin resistant patients. Because the major contributing factor for insulin resistance is currently considered to be the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), and because periodontal surgery may cause transient bacteremia which may up-regulate the serum TNF-alpha level, which in turn suppresses insulin action, patients should be strictly treated non-surgically and their serum TNF-alpha levels should be periodically monitored. On the other hand, diabetic patients positive for serum anti-glutamate decarboxylase auto-antibody should be examined for the source of this antibody, since 1) gingival and periodontal ligament fibroblasts were found to express glutamate decarboxylase, and 2) some otherwise healthy periodontitis patients develop anti-glutamate decarboxylase antibody. Thus, chronic periodontitis may influence the level of this antibody which is widely used as a predictive marker for slowly progressive insulin dependent diabetes mellitus. Not only is periodontal disease thereby affected by systemic diseases, but carefully managed periodontal therapy may also have a positive effect on the general health of patients with systemic diseases.
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PMID:Negative effects of chronic inflammatory periodontal disease on diabetes mellitus. 1266 61


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