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)

Actinobacillus actinomycetemcomitans is implicated in the pathogenesis of localized aggressive periodontitis, and has the capacity to express a cytolethal distending toxin (Cdt). Gingival fibroblasts (GF) are resident cells of the periodontium, which can express several osteolytic cytokines. The aims of this study were a) to investigate the role of Cdt in A. actinomycetemcomitans-induced expression of osteolytic cytokines and their cognate receptors in GF and b) to determine if the previously demonstrated induction of receptor activator of NFkappaB ligand (RANKL) by A. actinomycetemcomitans is mediated by these pro-inflammatory cytokines or by prostaglandin E(2) (PGE(2)). A. actinomycetemcomitans clearly induced interleukin (IL)-6, IL-1beta, and to a minimal extent, tumor necrosis factor (TNF)-alpha mRNA expression. At the protein level, IL-6 but not IL-1beta or TNF-alpha expression was stimulated. The mRNA expression of the different receptor subtypes recognizing IL-6, IL-1beta and TNF-alpha was not affected. A cdt-knockout strain of A. actinomycetemcomitans had similar effects on cytokine and cytokine receptor mRNA expression, compared to its parental wild-type strain. Purified Cdt stimulated IL-6, but not IL-1beta or TNF-alpha protein biosynthesis. Antibodies neutralizing IL-6, IL-1 or TNF-alpha, and the PGE(2) synthesis inhibitor indomethacin, did not affect A. actinomycetemcomitans-induced RANKL expression. In conclusion, a) A. actinomycetemcomitans induces IL-6 production in GF by a mechanism largely independent of its Cdt and b) A. actinomycetemcomitans-induced RANKL expression in GF occurs independently of IL-1, IL-6, TNF-alpha, or PGE(2).
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PMID:Cytokine responses of human gingival fibroblasts to Actinobacillus actinomycetemcomitans cytolethal distending toxin. 1580 96

Epithelial cells and macrophages play a major role in the host response to Porphyromonas gingivalis, a major etiologic agent of chronic periodontitis. Secretion of high levels of cytokines by these cells is believed to contribute to periodontal tissue destruction. To investigate the interactions between P. gingivalis and these two major cell types, we characterized the production of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and regulated on activation normal T cell expressed and secreted (RANTES) by an in vitro co-culture model composed of epithelial-like transformed cells (HeLa cell line) and macrophage-like cells (phorbol myristic acid-differentiated U937 cell line) following a challenge with different strains of P. gingivalis. P. gingivalis cells stimulated the secretion of pro-inflammatory cytokines (IL-1beta and IL-6) and chemokines (IL-8 and RANTES) in the co-culture model. Responses to P. gingivalis infection were influenced by the macrophage/epithelial cell ratios of the cultures. In addition, the level of secretion of these inflammatory mediators was dependent on the bacterial strain and the multiplicity of infection (MOI) used. The use of a gingipain-deficient mutant of P. gingivalis or the addition of a cysteine protease inhibitor suggested that the level of cytokines secreted by the co-culture model was underestimated due to an extensive proteolytic degradation. This study showed that P. gingivalis can modulate the levels of inflammatory mediators, which may contribute to the progression of periodontitis.
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PMID:Modulation of cytokine production by Porphyromonas gingivalis in a macrophage and epithelial cell co-culture model. 1581 35

Activated matrix metalloproteinase-3 (MMP-3) can contribute to periodontal ligament destruction in adult periodontitis. Since MMP-3 has been reported to activate proMMP-8 and -9, it was speculated that gingival tissue fibroblast-derived MMP-3 might, in periodontitis, be responsible for activation of gingival crevicular fluid (GCF) neutrophil-derived proMMP-8 and -9. Immunohistochemistry disclosed MMP-3 in gingival fibroblasts in periodontitis. Cultured gingival fibroblasts released only pro-MMP-3 when stimulated with tumor necrosis factor-alpha. However, Western blot revealed partially activated MMP-3, MMP-8, and MMP-9 in periodontitis GCF. Active MMP-8 (p < 0.05) and MMP-9 (p < 0.05) correlated with the presence of active MMP-3. It seems that resident gingival fibroblasts produce pro-MMP-3 in GCF, where it becomes activated, probably by cathepsin G or elastase released by neutrophils. Active MMP-3 then activates neutrophil-derived pro-MMP-8 and -9. Different tissue compartments/cells exert co-operative actions in mutual local MMP activation cascades.
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PMID:Gingival tissue and crevicular fluid co-operation in adult periodontitis. 1637 82

Many studies have attempted to define the relationship between postmenopausal osteoporosis and periodontal disease. Most studies support a positive association between these common diseases; however, many are cross-sectional in nature, include relatively small sample sizes, and have inadequate control of potential confounding factors, such as age, gender, hormone intake, race, and smoking, limiting our understanding of the nature of the relationship between these diseases. Clinical conditions causing low estrogen environments in postmenopausal women allow T- and B-cell abnormalities, increased local production of the bone-active cytokines (i.e., Interleukin-1, -6 and -8, tumor necrosis factor [TNF]-alpha) and a rise in prostaglandin E(2), resulting in the progression of periodontitis.
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PMID:[Osteoporosis and periodontal disease in postmenopausal women: association and mechanisms]. 1646 29

Monocytes/macrophages are key members of the innate immune system and are present in higher numbers in active periodontal lesions than in inactive sites. The aim of this study was to characterize the response of human monocyte U937 cells, differentiated into adherent macrophages by treatment with phorbol-12-myristate 13-acetate, to stimulation by Fusobacterium nucleatum ssp. nucleatum lipopolysaccharide. Attachment of (3)H-lipopolysaccharide to macrophage-like cells was partially inhibited by anti-CD14 and anti-TLR4 polyclonal antibodies. Fusobacterial lipopolysaccharide did not cause cell apoptosis or block apoptosis induced by camptothecin. Lipopolysaccharide up-regulated the secretion of the pro-inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha as well as the chemokine interleukin-8 by macrophage-like cells. In addition, it increased phospholipase C and D activities, which likely contributed to the high levels of prostaglandin E(2) detected in the cell culture supernatant. Lastly, the amount of matrix metalloproteinase-9 produced by macrophage-like cells was significantly increased by the lipopolysaccharide treatment. Interestingly, fusobacterial cells acquired matrix metalloproteinase-9 activity following incubation in the presence of the culture supernatant of lipopolysaccharide-stimulated macrophage-like cells. In summary, the lipopolysaccharide of F. nucleatum ssp. nucleatum has a large array of biological effects on macrophage-like cells. This monocytic responsiveness to lipopolysaccharide may be a key regulator of periodontitis.
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PMID:Response of human macrophage-like cells to stimulation by Fusobacterium nucleatum ssp. nucleatum lipopolysaccharide. 1662 77

Bone destruction is a pathological hallmark of several chronic inflammatory diseases, including rheumatoid arthritis, periodontitis, and osteoporosis. Inflammation-induced bone loss of this sort results from increased numbers of bone-resorbing osteoclasts. Numerous studies have indicated that conjugated linoleic acid (CLA) positively influences calcium and bone metabolism. Gene-deletion studies have shown that receptor activator of nuclear factor-kappaB ligand (RANKL) is one of the critical mediators of osteoclastogenesis. In this report, we examine the ability of CLA to suppress RANKL signaling and osteoclastogenesis in RAW264.7 cells, a murine monocytic cell line. Treatment of these cells with RANKL activated nuclear factor-kappaB (NF-kappaB), and preexposure of the cells to CLA significantly suppressed RANKL-induced NF-kappaB activation, including phosphorylation of I-kappaBalpha, degradation of I-kappaBalpha, and nuclear translocation of p65. RANKL induced osteoclastogenesis in these monocytic cells, and CLA inhibited RANKL-induced tumor necrosis factor-alpha production and osteoclast differentiation, including osteoclast-specific genes such as tartrate-resistant acid phosphatase, cathepsin K, calcitonin receptor, and matrix metalloproteinase-9 expression and osteoclast-specific transcription factors such as c-Fos, nuclear factor of activated T-cells expression, and bone resorption pit formation. CLA also inhibited RANKL-induced activation of mitogen-activated protein kinase p38 but had little effect on c-Jun N-terminal kinase activation. Collectively, these data demonstrate for the first time that CLA inhibits osteoclastogenesis by modulating RANKL signaling. Thus, CLA may have important therapeutic implications for the treatment of bone diseases associated with enhanced bone resorption by excessive osteoclastogenesis.
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PMID:Conjugated linoleic acid inhibits osteoclast differentiation of RAW264.7 cells by modulating RANKL signaling. 1670 1

Severe marginal periodontitis often coexists with diabetes and is considered to be the sixth complication of the disease. Several factors associated with diabetes have been shown to be related to the development and deterioration of diabetic periodontitis, i.e., glycated hemoglobin (HbA(1C)), advanced glycation endproducts (AGEs), C-reactive protein (CRP), and glucose tolerance, as well as inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. A periodontal pathogen, Porphyromonas gingivalis with the type II fimbria gene, is also considered to be a related infectious factor. Among them, AGEs seem to be closely associated with the periodontitis deterioration seen in diabetic subjects. Osteoporosis and diabetes are also tightly related, and AGEs have been reported to accelerate the progression of osteoporosis. Collectively, AGEs are a critical diabetic factor to deteriorate oral osteoporosis.
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PMID:[Diabetes and oral osteoporosis]. 1727 75

Periodontitis is characterized by periodontal tissue destruction. Since interleukin-17 (IL-17) has been reported to up-regulate IL-1beta and tumor necrosis factor-alpha (TNF-alpha), it was hypothesized that it is increased in periodontitis and up-regulates these cytokines and tissue-destructive matrix metalloproteinases (MMP) in local migrant and resident cells. Immunocytochemistry disclosed elevated IL-1beta, TNF-alpha, and IL-17 levels in periodontitis. These cytokines induced proMMP-1 and especially MMP-3 in gingival fibroblasts, whereas MMP-8 and MMP-9 were not induced. IL-17 was less potent as a direct MMP inducer than IL-1beta and TNF-alpha, but it induced IL-1beta and TNF-alpha production from macrophages, and IL-6 and IL-8 from gingival fibroblasts. In accordance with these findings, immunocytochemistry disclosed that MMP-1 and MMP-3 were increased in periodontitis. Gingival fibroblasts may play an important role in tissue destruction in periodontitis via cytokine-inducible MMP-1 and MMP-3 production, in which IL-17 plays a role as a key regulatory cytokine.
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PMID:MMPs, IL-1, and TNF are regulated by IL-17 in periodontitis. 1738 30

Growing evidence suggests that individual genetic susceptibility may influence the host's response to infections. The aim of this project was to study whether gene polymorphisms of inflammatory markers are associated with the presence of viable periodontopathogenic bacteria. We extracted genomic DNA from 45 young adults diagnosed with generalized aggressive periodontitis to study Fc receptors, formyl peptide receptor, Interleukin-6, tumor necrosis factor-alpha, and vitamin D receptor polymorphisms. The presence and viable numbers of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythensis were determined by culture, and their identities confirmed by PCR. Multiple logistic regressions revealed that both Fcgamma receptor and IL-6 -174 polymorphisms were associated with increased odds of detecting A. actinomycetemcomitans, P. gingivalis, and T. forsythensis after adjustment for age, ethnicity, smoking, and periodontitis extent. These findings support the hypothesis that complex interactions between the microbiota and host genome may be at the basis of susceptibility to aggressive periodontitis.
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PMID:Gene polymorphisms and the prevalence of key periodontal pathogens. 1745 60

Eugenol is commonly used as an analgesic agent during acute pulpitis and is a major component of root canal sealers. Despite the frequent applications of eugenol in the practice of dentistry, little is known about the role of eugenol under the status of inflammation. This study was aimed to investigate the influence of eugenol on human macrophages (U937) under the stimulation of lipopolysaccharide (LPS). Eugenol was shown to block the release of the bone resorbing mediators, including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and prostaglandin E2 from LPS-stimulated macrophages. In contrast, eugenol alone did not alter the expression levels of these proinflammatory mediators in macrophages. Consistent with downregulation of bone-resorbing mediators, eugenol suppressed the messenger RNA expression of LPS-induced IL-1beta, TNF-alpha, and cyclooxygenase-2 in macrophages. The results suggest a potential anti-inflammatory effect of eugenol in the acute inflamed pulps and apical periodontitis.
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PMID:Eugenol suppressed the expression of lipopolysaccharide-induced proinflammatory mediators in human macrophages. 1750 9


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