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)

Interleukin (IL)-1 and tumor necrosis factor (TNF) represent proinflammatory cytokines that stimulate a number of events which occur during periodontal disease. These include the induction of adhesion molecules and other mediators that facilitate and amplify the inflammatory response, the stimulation of matrix metalloproteinase, and bone resorption. The activity of these cytokines coincides with the critical events that occur during periodontal disease, namely, loss of attachment and bone resorption. The use of antagonists to IL-1 and TNF in experimental periodontitis have demonstrated a cause-and-effect relationship between the activity of these cytokines and the spread of an inflammatory front to deeper areas in the connective tissue, loss of connective tissue attachment, osteoclast formation, and loss of alveolar bone. In addition, the loss of fibroblasts that occurs during infection with periodontal pathogens is, in part, mediated by TNF. Thus, much of the damage that occurs during periodontal tissue destruction can be attributed to IL-1 and TNF activity. This destruction may very well represent an overreaction of the host response to periodontal pathogens caused by excessive production of IL-1 and TNF.
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PMID:The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. 1271 Jul 61

In the inflammatory gingival tissues of patients with periodontitis, cytokines such as interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha have been detected. Gingival fibroblasts are the major constituents of gingival tissue. We recently demonstrated that lipopolysaccharide (LPS) from periodontopathic bacteria induces inflammatory reactions in various tissues via CD14 and/or Toll-like receptors (TLRs) in gingival tissues [Biochem. Biophys. Res. Commun. 273 (2000) 1161]. To confirm this, we examined the expression of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, CD14, TLR2, and TLR4 in human gingival fibroblasts (HGFs) obtained from patients with healthy or inflammatory gingiva using DNA microarray analysis. We also studied the expression levels of these proteins by flow cytometric analysis (FACS). The expression levels of all eight genes in the HGFs of the Inflammatory group were significantly higher than those in the Healthy group on DNA microarray analysis. FACS revealed that the expression levels of all eight proteins on the HGFs of the Inflammatory group were higher than those on the Healthy group. Our data indicated that these eight proteins in HGFs are involved in inflammatory conditions in the gingiva, including periodontal disease. Our results suggested that these eight proteins, in turn, act directly or indirectly on the immune response by activating host cells involved in inflammatory processes.
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PMID:DNA microarray analysis of human gingival fibroblasts from healthy and inflammatory gingival tissues. 1276 25

Porphyromonas gingivalis, a major etiological agent of adult periodontitis, has two distinctly different types of fimbriae on the cell surface. The major fimbriae, which consist of a 41-kDa fimbrillin of P. gingivalis ATCC 33277, have been known to induce inflammatory cytokine production in murine peritoneal macrophages. In this study, we examined the effects of the minor fimbriae of P. gingivalis, composed of a 67-kDa fimbrillin, on cytokine production in murine peritoneal macrophages and the ability to induce osteoclast differentiation. Murine peritoneal macrophages were stimulated with P. gingivalis 67-kDa minor fimbriae for 24 h, then the levels of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-6 production were determined by enzyme-linked immunosorbent assay (ELISA). To estimate osteoclast differentiation, mouse osteoclast precursors were placed on dentine slices, and cultured with or without P. gingivalis 67-kDa minor fimbriae for 7 days. P. gingivalis 67-kDa minor fimbriae clearly induced IL-1beta, TNF-alpha and IL-6 production in mouse macrophages. Furthermore, pit formations on the dentine slices were significantly extended when the osteoclast precursors were incubated with P. gingivalis 67-kDa minor fimbriae. Pretreatment with anti-Toll-like receptor 2 (TLR2) antibody significantly inhibited IL-1beta, TNF-alpha and IL-6 induction (P<0.05) in mouse macrophages and pit-forming activity of osteoclast precursor cells stimulated with P. gingivalis 67-kDa minor fimbriae. These results suggest that P. gingivalis 67-kDa minor fimbriae may provoke host inflammatory response and be involved in periodontal tissue breakdown.
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PMID:Porphyromonas gingivalis 67-kDa fimbriae induced cytokine production and osteoclast differentiation utilizing TLR2. 1465 42

The presence of Porphyromonas gingivalis with type II fimA is strongly associated with adult periodontitis. However, the importance of specific fimA types in the immune response is unknown. Two types of P. gingivalis (type I and type II) and Actinomyces naeslundii were assessed for their degree of cytokine induction in the macrophage-like human cell line U937. Real-time reverse transcriptase polymerase chain reaction was used to determine mRNA expression of 12 cytokines. Significant levels of interleukin (IL)-8 induction and a similar cytokine expression pattern were observed at 6 h postinfection for all three bacterial strains. However, type II P. gingivalis infection showed statistically higher levels of IL-1beta, IL-8, IL-12 and tumor necrosis factor-alpha mRNA induction than those of control at 24 h postinfection, whereas type I P. gingivalis and A. naeslundii showed no significant induction of these cytokines. These data suggest that compared with A. naeslundii and type I P. gingivalis, type II P. gingivalis prolongs the cytokine response. Although other factors may also be involved, the sustained cytokine response induced by type II P. gingivalis may play an important role in enhanced periodontal tissue inflammation and destruction.
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PMID:Differential cytokine induction by two types of Porphyromonas gingivalis. 1487 53

We studied the inhibitory effect of Powerdental on the growth and acid production of Streptococcus mutans as well as secretion of pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). The growth of Streptococcus mutans was reduced by the presence of the Powerdental (1 mg/ml) and NaCl (1 mg/ml) significantly, and the positive control group (1% NaF) also exhibited a significant antibacterial activity. The decrease of pH was significantly inhibited in the presence of Powerdental (1 mg/ml) compared to the control group. The decrease in pH was also inhibited in the presence of positive control (1% NaF), but the bamboo salt alone did not show inhibitory activity. We also found that Powerdental (0.01 mg/ml) inhibited significantly the secretion of TNF-alpha with 46.5+/-0.2% from human mast cells. Our results suggest that Powerdental contributes to the prevention or treatment of periodontitis and other oral diseases or inflammatory diseases.
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PMID:Effect of Powerdental on caries-inducing properties of Streptococcus mutans and TNF-alpha secretion from HMC-1 cells. 1513 20

Bone destruction is a pathological hallmark of several chronic inflammatory diseases, including rheumatoid arthritis and periodontitis. Inflammation-induced bone loss of this sort results from elevated numbers of bone-resorbing osteoclasts. Gene targeting studies have shown that the transcription factor nuclear factor-kappa B (NF-kappa B) has a crucial role in osteoclast differentiation, and blocking NF-kappa B is a potential strategy for preventing inflammatory bone resorption. We tested this approach using a cell-permeable peptide inhibitor of the I kappa B-kinase complex, a crucial component of signal transduction pathways to NF-kappa B. The peptide inhibited RANKL-stimulated NF-kappa B activation and osteoclastogenesis both in vitro and in vivo. In addition, this peptide significantly reduced the severity of collagen-induced arthritis in mice by reducing levels of tumor necrosis factor-alpha and interleukin-1 beta, abrogating joint swelling and reducing destruction of bone and cartilage. Therefore, selective inhibition of NF-kappa B activation offers an effective therapeutic approach for inhibiting chronic inflammatory diseases involving bone resorption.
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PMID:Selective inhibition of NF-kappa B blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo. 1515 2

Our recent work showed that human periodontal ligament fibroblasts (HPLF) secrete bioactive osteoprotegerin (OPG), which inhibits osteoclastic differentiation and activity. However, it is unknown how HPLF regulate bone metabolism in the presence of lipopolysaccharide (LPS), which is a cell component of gram-negative bacteria and a pathogen in inflammatory bone diseases such as periodontitis. The present study examined the effects of Escherichia coli LPS on the gene expression of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), OPG, and receptor activator of NF-kappa B ligand (RANKL) in HPLF using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. In HPLF cultured with LPS for 48 h, expression of both OPG and RANKL mRNA was up-regulated, whereas for up to 24 h of stimulation, such up-regulation was not observed. However, LPS increased expression of IL-1 beta and TNF-alpha mRNA within 6 h of treatment. Moreover, in HPLF cultured with IL-1 beta or TNF-alpha, OPG and RANKL expression was induced within 12 h of culture. The administration of neutralizing antibodies against human IL-1 beta or TNF-alpha to LPS-treated cultures of HPLF inhibited the induction of OPG and RANKL expression. These suggest that LPS stimulates both OPG and RANKL expression in HPLF by up-regulating IL-1 beta and TNF-alpha. In addition, administration of conditioned medium (CM) from HPLF (HPLF-CM) stimulated with LPS for 48 h to mouse bone marrow culture failed to induce osteoclast-like cell (OCL) formation. When mouse spleen cells were cocultured with HPLF in the presence of LPS, OCL formation was completely blocked. Taken together, our results indicate that human periodontal ligament cells stimulated with LPS inhibit osteoclastogenesis by producing more effective OPG than RANKL via the induction of IL-1 beta and TNF-alpha.
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PMID:Lipopolysaccharide stimulates expression of osteoprotegerin and receptor activator of NF-kappa B ligand in periodontal ligament fibroblasts through the induction of interleukin-1 beta and tumor necrosis factor-alpha. 1533 98

During the last two decades, there has been an increasing interest in the impact of oral health on atherosclerosis and subsequent cardiovascular disease (CVD). The advent of the inflammation paradigm in coronary pathogenesis stimulated research in chronic infections caused by a variety of micro-organisms-such as Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus-as well as dental pathogens, since these chronic infections are thought to be involved in the etiopathogenesis of CVD by releasing cytokines and other pro-inflammatory mediators (e.g., C-reactive protein [CRP], tumor necrosis factor [TNF-alpha]) that may initiate a cascade of biochemical reactions and cause endothelial damage and facilitate cholesterol plaque attachment. Yet, due to the multi-factorial nature of dental infection and CVD, confirming a causal association is difficult, and the published results are conflicting. The main deficit in the majority of these studies has been the inadequate control of numerous confounding factors, leading to an overestimation and the imprecise measurement of the predictor or overadjustment of the confounding variables, resulting in underestimation of the risks. A meta-analysis of prospective and retrospective follow-up studies has shown that periodontal disease may increase the risk of CVD by approximately 20% (95% confidence interval [CI], 1.08-1.32). Similarly, the reported risk ratio between periodontal disease and stroke is even stronger, varying from 2.85 (CI 1.78-4.56) to 1.74 (CI 1.08-2.81). The association between peripheral vascular disease and oral health parameters has been explored in only two studies, and the resultant relative risks among individuals with periodontitis were 1.41 (CI 1.12-1.77) and 2.27 (CI 1.32-3.90), respectively. Overall, it appears that periodontal disease may indeed contribute to the pathogenesis of cardiovascular disease, although the statistical effect size is small.
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PMID:Oral health, atherosclerosis, and cardiovascular disease. 1557 81

There has been a resurgence of interest in recent years in the systemic effects of oral infections such as periodontal diseases. The study of the various means by which periodontal infections and inflammation may influence a variety of systemic conditions is collectively referred to as periodontal medicine. The periodontium responds to tooth-borne biofilm (dental plaque) by the process of inflammation. Dental biofilms release a variety of biologically active products, such as bacterial lipopolysaccharides (endotoxins), chemotactic peptides, protein toxins, and organic acids. These molecules stimulate the host to produce a variety of responses, among them the production and release of potent agents known as cytokines. These include interleukin-1 beta, interleukin-8, prostaglandins, and tumor necrosis factor-alpha. There is a spectrum of periodontal response to these molecules, from mild gingivitis to severe destructive periodontitis. These and other host products and responses may influence a variety of important disease pathways, including atherosclerosis, mucosal inflammation, and premature parturition. The purpose of this article is to review the possible biological pathways by which periodontal diseases may influence these disease processes.
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PMID:Periodontal inflammation: from gingivitis to systemic disease? 1564 83

Bacterial plaque has been shown to initiate periodontal diseases. Most studies indicate that the host response, rather than the direct effect of bacteria, is responsible for much of the destruction associated with periodontitis. Bacteria or their products have an indirect role by stimulating inflammation, which is associated with the excessive production of inflammatory mediators, such as prostaglandins, or cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1. These mediators, in turn, induce the production and activation of enzymes that destroy gingival connective tissue and stimulate the formation of osteoclasts to resorb bone. Based on results in animal models and studies in humans showing that similar responses occur, the initial steps in the breakdown of connective tissue attachment to the tooth surface and bone resorption involve the production of inflammatory cytokines. Moreover, the risk and severity of periodontal diseases is affected by systemic factors, such as diabetes. Diabetes in particular seems to impair the ability to produce new bone formation after bone loss by preventing the formation of new bone that normally occurs after bone is resorbed, a process called coupling. In addition, the cytokines that stimulate loss of tissue, particularly TNF-alpha, may kill the cells that repair damaged connective tissue or bone. In diabetes there may be more TNF-alpha produced, leading to an even more limited capacity to repair tissue. The diminished capacity to form new bone may make it more difficult for diabetics in particular to repair the loss of tissue that occurs in periodontal diseases.
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PMID:Evidence that diabetes mellitus aggravates periodontal diseases and modifies the response to an oral pathogen in animal models. 1564 85


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