UMLS:C0031099 - FACTA Search

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

Accumulated evidence points to Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia as three major etiologic agents of chronic periodontitis. Epithelial cells and macrophages play a major role in the host response to periodontopathogens, and the secretion of inflammatory mediators and matrix metalloproteinases (MMPs) by these host cells is believed to contribute to periodontal tissue destruction. The aim of this study was to investigate the inflammatory response of a macrophage/epithelial cell co-culture model following mono or mixed infections with the above three periodontopathogens. An in vitro co-culture model composed of epithelial-like transformed cells (HeLa cell line) and macrophage-like cells (phorbol myristic acid-differentiated U937 monocytic cell line) was challenged with whole cells or lipopolysaccharides (LPS) of P. gingivalis, T. denticola, and T. forsythia, individually and in combination. Following stimulation, the production of interleukin-1 beta (IL-1beta), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), regulated on activation normal T cell expressed and secreted (RANTES), prostaglandin E2 (PGE2), and MMP-9 were quantified by enzyme-linked immunoassays. We observed that mono or mixed infections of the co-culture model induced the secretion of IL-1beta, IL-6, IL-8, PGE2, and MMP-9. P. gingivalis and T. forsythia induced an increase in RANTES secretion, whereas T. denticola alone or in combination resulted in a significant decrease in RANTES levels. All LPS challenges induced an increase in chemokine, MMP-9, and PGE2 production. No synergistic effect on the production of cytokines, chemokines, PGE2, and MMP-9 was observed for any of the bacterial or LPS mixtures tested. This study supports the view that P. gingivalis, T. denticola, and T. forsythia may induce high levels of pro-inflammatory mediators and MMP-9 in periodontal lesions, thus contributing to the progression of periodontitis.
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PMID:Inflammatory responses of a macrophage/epithelial cell co-culture model to mono and mixed infections with Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. 1615 71

Porphyromonas gingivalis is one of the suspected periodontopathic bacteria. The lipopolysaccharide (LPS) of P. gingivalis is a key factor in the development of periodontitis. Inflammatory cytokines play important roles in the gingival tissue destruction that is a characteristic of periodontitis. Macrophages are prominent at chronic inflammatory sites and are considered to contribute to the pathogenesis of periodontitis. Xylitol stands out and is widely believed to possess anticaries properties. However, to date, little is known about the effect of xylitol on periodontitis. The aim of the present study was to determine tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) expression when RAW 264.7 cells were stimulated with P. gingivalis LPS (hereafter, LPS refers to P. gingivalis LPS unless stated otherwise) and the effect of xylitol on the LPS-induced TNF-alpha and IL-1beta expression. The kinetics of TNF-alpha and IL-1beta levels in culture supernatant after LPS treatment showed peak values at 1 h (TNF-alpha) and 2 to 4 h (IL-1beta), respectively. NF-kappaB, a transcription factor, was also activated by LPS treatment. These cytokine expressions and NF-kappaB activation were suppressed by pretreatment with pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB). Pretreatment with xylitol inhibited LPS-induced TNF-alpha and IL-1beta gene expression and protein synthesis. LPS-induced mobilization of NF-kappaB was also inhibited by pretreatment with xylitol in a dose-dependent manner. Xylitol also showed inhibitory effect on the growth of P. gingivalis. Taken together, these findings suggest that xylitol may have good clinical effect not only for caries but also for periodontitis by its inhibitory effect on the LPS-induced inflammatory cytokine expression.
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PMID:Xylitol inhibits inflammatory cytokine expression induced by lipopolysaccharide from Porphyromonas gingivalis. 1627 42

Smoking has deleterious effects on osteoporosis and periodontitis both characterized by bone loss. Smoking also interferes with the protective effect that hormone replacement therapy (HRT) has on bone loss. Our study investigated two mechanisms by which smoking may affect bone metabolism: nicotine-induced proliferation and nicotine-induced cytokine secretion in osteoblasts. Two osteoblastic cell models were used: mouse osteoblasts derived from mouse calvaria and human osteoblasts. Thymidine incorporation and immunoassays were used to evaluate proliferation, interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) secretion. Parametric and nonparametric statistical analyses were used for comparisons. The results showed that nicotine induced stimulation and inhibition of proliferation in both osteoblastic cell models. In human osteoblasts, the proliferative and inhibitory effects were also donor dependent. Il-6 secretion showed different patterns in mouse and human osteoblasts. In mouse osteoblasts, nicotine significantly increased IL-6 secretion and estradiol significantly inhibited the nicotine-induced IL-6 release. In human osteoblasts, cells derived from one subject did not respond to nicotine. However, in the second sample, nicotine increased secretion of Il-6 but estradiol did not oppose this effect. In human osteoblasts, nicotine also induced an increase in the TNF-alpha secretion and estradiol opposed this increase. These results suggest that nicotine affects bone metabolism by modulating proliferation, and Il-6 and TNF-alpha secretion. These studies provide a possible explanation for differences in bone loss among subjects who smoke and offer a possible mechanism for the oppositional effect of smoking on HRT in subjects with bone loss.
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PMID:Nicotine induced proliferation and cytokine release in osteoblastic cells. 1632 20

Periodontitis is a chronic inflammatory disease affecting oral tissues. The continuous, high production of cytokines by host cells triggered by periodontopathogens is thought to be responsible for the destruction of tooth-supporting tissues. Macrophages play a critical role in this host inflammatory response to periodontopathogens. The aim of this study was to investigate the effect of non-dialyzable material prepared from cranberry juice concentrate on the pro-inflammatory cytokine response of macrophages induced by lipopolysaccharides (LPS) from Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum subsp. nucleatum, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Escherichia coli. Interleukin-1 beta (IL-1beta), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and Regulated on Activation Normal T-cell Expressed and Secreted (RANTES) production by macrophages treated with the cranberry fraction prior to stimulation by LPS was evaluated by ELISA. Our results clearly indicate that the cranberry fraction was a potent inhibitor of the pro-inflammatory cytokine and chemokine responses induced by LPS. This suggests that cranberry constituents may offer perspectives for the development of a new therapeutic approach to the prevention and treatment of periodontitis.
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PMID:Anti-inflammatory activity of a high-molecular-weight cranberry fraction on macrophages stimulated by lipopolysaccharides from periodontopathogens. 1649 70

It was hypothesized that peri-implant tissue around loosening dental implants may contain cytokines with a potential to regulate osteoclasts. Peri-implant and/or gingival samples from loosened implants, chronic periodontitis (CP), and normal controls (n = 10 samples in each group) were analyzed using immunohistochemical staining to observe tumor necrosis factor alpha (TNF-alpha), interleukin 1-alpha (IL-1alpha), IL-6, platelet-derived growth factor A (PDGF-A), and transforming growth factor alpha (TGF-alpha). These cytokines were found in foreign-body giant cells, macrophages, fibroblasts, and epithelial cells. TNF-alpha, IL-1alpha, and IL-6 were increased (P < .05; unpaired t test) in peri-implantitis and CP, whereas PDGF-A and TGF-alpha were not. In conclusion, cytokines with a potential to activate osteoclasts were found in both peri-implantitis and CP, but the cytokine profiles differed in that IL-1alpha was the most prevalent cytokine in the former and TNF-alpha was the most common in the latter. These cytokines may contribute to peri-implant bone loss/loosening by stimulating formation and activity of osteoclasts and might be an amenable target for local therapies with cytokine modulators.
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PMID:Immunohistochemical evaluation of inflammatory mediators in failing implants. 1664 2

Antimicrobial peptides, human beta-defensin (hBD), and the 18-kDa cationic antimicrobial protein (CAP18) are components of innate immunity. These peptides have antimicrobial activity against bacteria, fungi, and viruses. Actinobacillus actinomycetemcomitans is a gram-negative facultative anaerobe implicated in the initiation of periodontitis. The innate immunity peptides have antibacterial activity against A. actinomycetemcomitans. We investigated the molecular mechanism of human gingival epithelial cells (HGEC) responding to exposure to A. actinomycetemcomitans. HGEC constitutively express hBD1 and inducibly express hBD2, hBD3, and CAP18 on exposure to A. actinomycetemcomitans. The level of expression varies among clinical isolates. In the signaling pathway for hBD2 induction by the bacterial contact, we demonstrate that the mitogen-activated protein (MAP) kinase and not the NF-kappaB transcription factor pathway is used. We found the outer membrane protein 100 (Omp100; identified by molecular mass) is the component inducing the hBD2 response. Omp100 binds to fibronectin, an extracellular matrix inducing hBD2 via the MAP kinase pathway. Anti-integrin alpha(5)beta(1), antifibronectin, genistein, and PP2 suppress the Omp100-induced expression of hBD2, suggesting that Src kinase is involved through integrin alpha(5)beta(1). The inflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6 and IL-8, produced by HGEC on contact with A. actinomycetemcomitans also stimulate expression of hBD2. Further, neutralizing antibody against TNF-alpha or IL-8 partially inhibits the induction of hBD2 on bacterial contact. Therefore, we found that the induction of the antimicrobial peptides is mediated by a direct response principally through an Omp100-fibronectin interaction, and using secondary stimulation by inflammatory cytokines induced by the bacterial exposure.
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PMID:Actinobacillus actinomycetemcomitans outer membrane protein 100 triggers innate immunity and production of beta-defensin and the 18-kilodalton cationic antimicrobial protein through the fibronectin-integrin pathway in human gingival epithelial cells. 1692 14

Humans develop periodontitis in response to challenge by microbial dental plaque. Inflammation begins after perturbation of gingival epithelial cells by subgingival bacteria interacting through pattern-recognition receptors, including the Toll-like receptors (TLR). Porphyromonas gingivalis is a major periodontopathogen that interacts with epithelial cells through its cell surface fimbriae (FimA), leading to colonization and/or invasion. Previous work by our group has established membrane CD14 as an essential coreceptor for TLR2-mediated activation of transfected cell lines by P. gingivalis FimA. We have shown that gingival epithelial cells express TLR2 but not CD14 on their cell surfaces. We thus speculated that P. gingivalis FimA does not readily activate epithelial innate immune responses but rather functions to promote P. gingivalis colonization in the absence of a vigorous FimA-induced response. This hypothesis was verified by the findings that primary human gingival epithelial cells responded poorly to FimA in terms of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha responses, in stark contrast to the marked response to other TLR2 agonists (Pam3Cys, FSL-1) that are not strictly dependent on CD14. On the other hand, CD14-expressing human primary monocytes responded with high levels of the same cytokines to both FimA and the control TLR2 agonists. The gingival epithelial cells failed to respond to FimA even in the presence of exogenously added soluble CD14. These data indicate that the gingival epithelial cell hyporesponsiveness to FimA is attributable to the lack of membrane-expressed but not soluble CD14. In conclusion, P. gingivalis FimA differentially activates human monocytes and epithelial cells, perhaps reflecting different tactics used by P. gingivalis when interacting with different host cell types or a host strategy to limit inflammation.
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PMID:Differential activation of human gingival epithelial cells and monocytes by Porphyromonas gingivalis fimbriae. 1711 77

Vascular disruption and bleeding during periodontitis likely increase the levels of hemoglobin in gingival crevicular fluid. The aim of this study was to investigate the effect of hemoglobin on the inflammatory responses of human macrophages stimulated with lipopolysaccharides (LPS) isolated from periodontopathogens. The production of interleukin-1 beta (IL-1beta), IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) by macrophages following challenges with Porphyromonas gingivalis and Fusobacterium nucleatum LPS in the presence or absence of human hemoglobin was analyzed by ELISA. The effect of hemoglobin on LPS-binding to macrophages was evaluated with (3)H-LPS. Hemoglobin and LPS from periodontopathogens acted in synergy to stimulate the production of high levels of IL-1beta, IL-6, IL-8, and TNF-alpha by macrophages. Hemoglobin also enhanced LPS-binding to macrophages. This study suggests that hemoglobin contributes to increases in the levels of pro-inflammatory mediators in periodontal sites by acting in synergy with LPS from periodontopathogens, thus favoring the progression of periodontitis.
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PMID:Hemoglobin and LPS act in synergy to amplify the inflammatory response. 1772 Aug 59

Generalized aggressive periodontitis (GAP) comprises a group of periodontal diseases characterized by the rapid destruction of periodontal tissues which affect young individuals who generally present no systemic disorders. Polymorphisms in the interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) genes have been associated with an increased severity of chronic periodontitis. The objective of the present study was to evaluate the association between IL-1A (-889) and TNFA (-308) gene polymorphisms and GAP. One hundred nonsmoking subjects were selected, including 30 with GAP and 70 without periodontal disease. Gene polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. For IL-1 (-889), the frequency of genotype 1/1 was 54.3% in the control group and 56.7% in the study group. The frequency of genotype 1/2 was 37.1% in the control group and 40% in the study group. Genotype 2/2 was detected at a frequency of 8.6% and 3.3% in the control and study groups, respectively. For TNFA, genotype 1/1 was present in 68.6% of control subjects and in 80.0% of patients with GAP, while the frequency of genotype 1/2 was 27.1% in the control group and 20% in the study group. Genotype 2/2 was present in 4.3% of control subjects and was not detected in the study group. The frequencies of allele 1 and allele 2 of the IL-1A (-889) gene were 72.9% and 27.1%, respectively, in the control group and 76.7% and 23.3% in the GAP group. For the TNFA (-308) gene, the frequency of allele 1 was 82.15% in the control group and 90% in the study group, whereas the frequency of allele 2 was 17.85% in the control group and 10% in the study group. Statistical analysis revealed no significant difference in allele distribution for either gene between the two groups. No association was observed between GAP and IL-1A (-889) and TNFA (-308) gene polymorphisms in Brazilian patients.
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PMID:Analysis of IL-1A(-889) and TNFA(-308) gene polymorphism in Brazilian patients with generalized aggressive periodontitis. 1782 82

Periodontitis is a chronic human inflammatory disease initiated and sustained by dental plaque microorganisms. A major contributing pathogen is Porphyromonas gingivalis, a gram-negative bacterium recognized by Toll-like receptor 2 (TLR2) and TLR4, which are expressed by human gingival epithelial cells (HGECs). However, it is still unclear how these cells respond to P. gingivalis and initiate inflammatory and immune responses. We have reported previously that HGECs produce a wide range of proinflammatory cytokines, including interleukin-6 (IL-6), IL-8, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha (TNF-alpha), and IL-1beta. In this study, we show that IL-1beta has a special role in the modulation of other inflammatory cytokines in HGECs challenged with P. gingivalis. Our results show that the increased production of IL-1beta correlates with the cell surface expression of TLR4, and more specifically, TLR4-normal HGECs produce fourfold more IL-1beta than do TLR4-deficient HGECs after challenge. Moreover, blocking the IL-1beta receptor greatly reduces the production of "secondary" proinflammatory cytokines such as IL-8 or IL-6. Our data indicate that the induction of IL-1beta plays an important role in mediating the release of other proinflammatory cytokines from primary human epithelial cells following challenge with P. gingivalis, and this process may be an inflammatory enhancement mechanism adopted by epithelial cells.
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PMID:Interleukin-1beta modulates proinflammatory cytokine production in human epithelial cells. 1833 11

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