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)

We investigated the effects of inflammatory cytokines and periodontopathic bacteria on expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1, and E-selectin (endothelial leukocyte adhesion molecule 1) in cultured human gingival fibroblasts (HGF). Cell surface ICAM-1 was upregulated on HGF under transcriptional control by exposure not only to interleukin-1 beta, tumor necrosis factor alpha, and gamma interferon but also to sonic extracts prepared from Porphyromonas gingivalis and Prevotella intermedia (nigrescens) and lipopolysaccharides from Escherichia coli. However, these stimuli induced only minimal expression of vascular cell adhesion molecule 1 and E-selectin on HGF. Binding assays using HGF and Molt 4, the human T-cell leukemia cell line, showed induced ICAM-1 to be functional, and the increased binding was blocked by a combination of monoclonal antibodies against ICAM-1 and leukocyte function-associated antigen 1. Furthermore, gingival tissues from adult periodontitis patients showed increased mRNA expression of ICAM-1 compared with that in tissues from normal healthy donors. In immunohistological analysis, we also observed in vivo that the expression of ICAM-1 on fibroblasts in adult periodontitis tissues was greater than that in normal gingiva. Thus, the overexpression of ICAM-1 on gingival fibroblasts induced by cytokines and periodontopathic bacteria is speculated to be deeply involved in the accumulation and retention of leukocyte function-associated antigen 1-bearing leukocytes in adult periodontitis lesions.
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PMID:Effects of cytokines and periodontopathic bacteria on the leukocyte function-associated antigen 1/intercellular adhesion molecule 1 pathway in gingival fibroblasts in adult periodontitis. 752 81

Intercellular adhesion molecule 1 (ICAM-1) is involved in the accumulation and activation of leukocytes in inflammatory diseases such as periodontitis. As reported previously, ICAM-1 is up-regulated on cultured human gingival fibroblasts (HGF) by exposure to lipopolysaccharide (LPS), suggesting a specific LPS recognition mechanism. We therefore investigated the role of CD14, an LPS receptor, in stimulation of HGF by LPS. Cell surface CD14 antigen was not observed on HGF by flow cytometric analysis. In addition, expression of CD14 mRNA in HGF was not detected by reverse transcription-PCR analysis. Since HGF did not express endogenous CD14, we investigated the role of human serum-derived soluble CD14 (sCD14) in ICAM-1 induction on HGF by LPS. The serum-dependent ICAM-1 induction by LPS was observed in HGF. In medium containing human serum, anti-CD14 antibody inhibited ICAM-1 induction on HGF by LPS. Depletion of sCD14 from human serum markedly reduced ICAM-1 expression on HGF in response to LPS. Supplementation of the serum-free medium with sCD14 alone restored the capacity of HGF to respond to LPS. These results show that induction of ICAM-1 in HGF by LPS does not involve binding to cell surface CD14 but is mediated by serum-derived sCD14.
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PMID:Soluble CD14 mediates lipopolysaccharide-induced intercellular adhesion molecule 1 expression in cultured human gingival fibroblasts. 894 31

Treponema maltophilum and Treponema lecithinolyticum belong to the group IV oral spirochetes and are associated with endodontic infections, as well as periodontitis. Recently, the genes encoding the major surface proteins (Msps) of these bacteria (MspA and MspTL, respectively) were cloned and sequenced. The amino acid sequences of these proteins showed significant similarity. In this study we analyzed the functional role of these homologous proteins in human monocytic THP-1 cells and primary cultured periodontal ligament (PDL) cells using recombinant proteins. The complete genes encoding MspA and MspTL without the signal sequence were cloned into Escherichia coli by using the expression vector pQE-30. Fusion proteins tagged with N-terminal hexahistidine (recombinant MspA [rMspA] and rMspTL) were obtained, and any possible contamination of the recombinant proteins with E. coli endotoxin was removed by using polymyxin B-agarose. Flow cytometry showed that rMspA and rMspTL upregulated the expression of intercellular adhesion molecule 1 (ICAM-1) in both THP-1 and PDL cells. Expression of proinflammatory cytokines, such as interleukin-6 (IL-6) and IL-8, was also induced significantly in both cell types by the Msps, as determined by reverse transcription-PCR and an enzyme-linked immunosorbent assay, whereas IL-1beta synthesis could be detected only in the THP-1 cells. The upregulation of ICAM-1, IL-6, and IL-8 was completely inhibited by pretreating the cells with an NF-kappaB activation inhibitor, l-1-tosylamido-2-phenylethyl chloromethyl ketone. This suggests involvement of NF-kappaB activation. The increased ICAM-1 and IL-8 expression in the THP-1 cells obtained with rMsps was not inhibited in the presence of the IL-1 receptor antagonist (IL-1ra), a natural inhibitor of IL-1. Our results show that the Msps of the group IV oral spirochetes may play an important role in amplifying the local immune response by continuous inflammatory cell recruitment and retention at an infection site by stimulation of expression of ICAM-1 and proinflammatory cytokines.
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PMID:Upregulation of intercellular adhesion molecule 1 and proinflammatory cytokines by the major surface proteins of Treponema maltophilum and Treponema lecithinolyticum, the phylogenetic group IV oral spirochetes associated with periodontitis and endodontic infections. 1561 63

Porphyromonas gingivalis, a periodontopathic bacterium, is known to invade oral epithelial cells in periodontal lesions, although the mechanism is unclear. In the present study, goat polyclonal anti-intercellular adhesion molecule 1 (anti-ICAM-1) antibody inhibited the invasion of P. gingivalis into KB cells (human oral epithelial cells). Further, the P. gingivalis fimbria, a pathogenic adhesion molecule, bound to recombinant human ICAM-1, as shown by enzyme-linked immunosorbent assay. P. gingivalis was also found to colocalize with ICAM-1 on KB cells, as seen with an immunofluorescence microscope, and the knockdown of ICAM-1 in KB cells resulted in the inhibition of P. gingivalis invasion by RNA interference. In addition, methyl-beta-cyclodextrin, a cholesterol-binding agent, inhibited the colocalization of P. gingivalis with ICAM-1 and invasion by the microorganism. The colocalization of caveolin-1, a caveolar marker protein, on KB cells with P. gingivalis was also shown, and the knockdown of caveolin-1 in KB cells caused a reduced level of P. gingivalis invasion. These results suggest that ICAM-1 and caveolae are required for the invasion of P. gingivalis into human oral epithelial cells, and these molecules appear to be associated with the primary stages of the development and progression of chronic periodontitis.
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PMID:Requirement for intercellular adhesion molecule 1 and caveolae in invasion of human oral epithelial cells by Porphyromonas gingivalis. 1617

Porphyromonas gingivalis has been implicated as a key etiologic agent in the pathogenesis of destructive chronic periodontitis. Among virulence factors of this organism are cysteine proteinases, or gingipains, that have the capacity to modulate host inflammatory defenses. Intercellular adhesion molecule expression by vascular endothelium represents a crucial process for leukocyte transendothelial migration into inflamed tissue. Ligation of CD99 on endothelial cells was shown to induce expression of endothelial leukocyte adhesion molecule 1, vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and major histocompatibility complex class II molecules and to increase adhesion of leukocytes. CD99 ligation was also found to induce nuclear translocation of NF-kappaB. These results indicate that endothelial cell activation by CD99 ligation may lead to the up-regulation of adhesion molecule expression via NF-kappaB activation. However, pretreatment of endothelial cells with gingipains caused a dose-dependent reduction of adhesion molecule expression and leukocyte adhesion induced by ligation of CD99 on endothelial cells. The data provide evidence that the gingipains can reduce the functional expression of CD99 on endothelial cells, leading indirectly to the disruption of adhesion molecule expression and of leukocyte recruitment to inflammatory foci.
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PMID:Gingipains of Porphyromonas gingivalis modulate leukocyte adhesion molecule expression induced in human endothelial cells by ligation of CD99. 1649 37

The periodontal vasculature is profoundly affected during the progression of periodontitis, and several specific bacteria are believed to be involved in this inflammatory disease. Eikenella corrodens is one of the common bacteria detected in periodontitis diseased lesions; however, the function of this organism in periodontitis is not well understood. In this study, we investigated the E. corrodens-induced endothelial cell alteration and inflammation process that leads to leukocyte infiltration in inflamed regions. Soluble products from E. corrodens (EcSP) induced the gene expression and protein production of vascular endothelial growth factor in oral epithelial cells and human umbilical vein endothelial cells (HUVEC). Direct stimulation by EcSP also activated endothelial cell proliferation. Moreover, EcSP induced ERK1/2 (p44/42) and p38 mitogen-activated protein kinase (MAPK) phosphorylation within 10-30 min in HUVEC, as demonstrated by Western blot analysis and up-regulated intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin and interleukin-8 (IL-8) production demonstrated by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. The specific p38 MAPK inhibitor SB203580 reduced the expression of ICAM-1, VCAM-1 and IL-8, whereas the blockade of p44/42 by MAPK kinase (MEK1) inhibitor, PD98059, inhibited only IL-8 expression. Our results indicate that E. corrodens can trigger a cascade of events that induce inflammatory responses in periodontal tissue via the MAPK cascade and may promote chronic periodontitis without bacteria-cell contact.
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PMID:Soluble products from Eikenella corrodens induce cell proliferation and expression of interleukin-8 and adhesion molecules in endothelial cells via mitogen-activated protein kinase pathways. 1724 Nov 69

It has been hypothesized that the neutrophil chemoattractant interleukin-8 (IL-8) forms a gradient in the oral cavity, with the highest concentration of IL-8 produced closest to the bacterial biofilm. In periodontitis, this gradient is disrupted, impairing neutrophil chemotaxis to diseased sites. Treponema denticola is prominently associated with periodontal disease, yet little is known about its ability to modulate the production of inflammatory mediators by epithelial cells. Others have shown that dentilisin, the major outer membrane protease of T. denticola, degrades IL-8 in vitro. We now provide evidence that T. denticola also fails to induce IL-8 production from primary gingival epithelial cells (PGEC). The lack of IL-8 production is not explained by IL-8 degradation, because a protease mutant that does not degrade IL-8 does not induce IL-8 production with these stimuli either. The lack of innate immune mediator production may be a more global phenomenon because T. denticola fails to induce IL-6 or intercellular adhesion molecule 1 production from PGEC. T. denticola also fails to induce transcription of IL-8 and human beta-defensin-2 messenger RNA. The lack of immune mediator production is not explained by the failure of T. denticola to interact with Toll-like receptor 2 (TLR-2), as T. denticola stimulates nuclear factor-kappaB nuclear translocation in TLR-2-transfected HEK293 cells. Not only can T. denticola degrade the IL-8 present in the periodontal lesion, but this organism also fails to induce IL-8 production by PGEC. The lack of an epithelial cell response to T. denticola may contribute to the pathogenesis of periodontitis by failing to trigger chemotaxis of neutrophils into the periodontal pocket.
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PMID:Treponema denticola does not induce production of common innate immune mediators from primary gingival epithelial cells. 1895 53

The RgpA-Kgp proteinase-adhesin complexes of Porphyromonas gingivalis were observed, using immunostaining, in human gingival tissue associated with periodontitis but not in healthy tissue. The staining pattern suggested a concentration gradient from the subgingival plaque into the subjacent gingival connective tissue. Intense immunostaining was observed in areas displaying gross disturbance of tissue architecture. P. gingivalis cells and the RgpA-Kgp complexes at low concentrations were shown to stimulate secretory intercellular adhesion molecule 1, interleukin-8 (IL-8), IL-6, and macrophage chemoattractant protein secretion from cultured human epithelial (KB) and fibroblast (MRC-5) cells. However, at high concentrations a reduction in the level of these mediators was observed. In contrast, macrophage inflammatory protein 1alpha and IL-1alpha were stimulated only at high P. gingivalis cell concentrations. P. gingivalis cells and the RgpA-Kgp complexes were shown to induce apoptosis in KB and MRC-5 cells in a time- and dose-dependent manner. These data suggest that the RgpA-Kgp complexes penetrate the gingival connective tissue; at low concentrations distal from the plaque the complexes stimulate the secretion of proinflammatory mediators, while at high concentrations proximal to the plaque they induce apoptosis and attenuate the secretion of proinflammatory mediators.
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PMID:Porphyromonas gingivalis RgpA-Kgp proteinase-adhesin complexes penetrate gingival tissue and induce proinflammatory cytokines or apoptosis in a concentration-dependent manner. 1911 47

In this study, we investigated the antibacterial activity of eight antimicrobial peptides (AMPs), comprising four human beta-defensins (HBDs), three human neutrophil defensins (HNPs) and the cathelicidin LL-37, against two representative periodontopathogens, Prevotella intermedia and Tannerella forsythia. The neutralising effect of these AMPs on expression of interleukin (IL)-1beta, IL-8 and intercellular adhesion molecule 1 (ICAM-1) induced by lipopolysaccharide (LPS) from P. intermedia and T. forsythia was also tested in THP-1 cells and human gingival fibroblasts. Prevotella intermedia was susceptible to HBD-3 and LL-37 but was resistant to HBD-1, HBD-2, HBD-4, HNP-1, HNP-2 and HNP-3 at concentrations up to 10microM. However, all of the AMPs except HNP-2 at 5microM significantly inhibited the expression of IL-1beta, IL-8 and ICAM-1 induced by P. intermedia LPS. Tannerella forsythia showed marked susceptibility to the AMPs tested in the following order: LL-37, HBD-3, HBD-2, HBD-1, HNP-1 and HBD-4. All of the AMPs except HNP-3 had significant neutralising effects on T. forsythia LPS activity. The AMPs showing LPS-neutralising activity inhibited LPS binding to the cells. These results suggest that AMPs may be considered as preventive and therapeutic agents against mixed bacterial infections such as periodontitis by eliminating the pathogens themselves as well as reducing the activity of LPS.
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PMID:Antibacterial and lipopolysaccharide (LPS)-neutralising activity of human cationic antimicrobial peptides against periodontopathogens. 2000 68

Infection and inflammation are risk factors in the initiation and progression of atherosclerosis. Periodontitis is one of the most prevalent chronic inflammations of the oral cavity, and has been reported to be associated with systemic disease. In this study, we evaluated whether the heat-shock protein GroEL of Fusobacterium nucleatum, one of the most prevalent bacteria in periodontitis, induces factors that predispose to atherosclerosis in human microvascular endothelial cells (HMEC-1) and apolipoprotein E-deficient (ApoE(-/-)) mice. GroEL induced the expression of chemokines such as monocyte chemoattractant protein-1 and interleukin-8 as well as cell adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin. GroEL induced the activity of tissue factor and reduced the activity of the tissue factor pathway inhibitor. Foam cell formation was induced by GroEL. GroEL-injected ApoE(-/-) mice showed significant atherosclerotic lesion progression compared with control mice. Serum levels of risk factors for atherosclerosis such as interleukin-6, C-reactive protein, and low-density lipoprotein were increased in GroEL-injected ApoE(-/-) mice compared with control mice, whereas serum levels of high-density lipoprotein were decreased. We could detect significantly higher levels of anti-F. nucleatum GroEL antibody in serum and F. nucleatum DNA in gingival crevicular fluid from patients with periodontitis than in that from healthy subjects. Our results indicate that the host response to the GroEL of periodontal pathogens like F. nucleatum may be a mechanism involved in atherosclerosis, supporting the association of periodontitis and systemic infection.
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PMID:Fusobacterium nucleatum GroEL induces risk factors of atherosclerosis in human microvascular endothelial cells and ApoE(-/-) mice. 2239 69


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