Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study evaluated the reproducibility of in-vitro-grown biofilms, initiated with subgingival plaque from patients with periodontal disease, and continued through several cycles by re-inoculating new biofilms from previously grown biofilms. Subgingival plaque samples from bleeding pockets along with saliva samples were collected from three patients with chronic periodontitis and perpetuated through seven cycles. Calcium hydroxyapatite disks were coated with sterilized saliva inoculated with dispersed subgingival plaque. The biofilms were grown anaerobically at 37 degrees C for 10 days, and at specific intervals total viable bacteria were enumerated and the species present were analysed by DNA-DNA checkerboard hybridization. All cycles of biofilm growth occurred at similar rates and reached steady-state at day 7. No statistically or microbially significant differences were found for viable counts or species present, at the same period of maturation, among the different cycles. This study demonstrated that growth of certain target subgingival periodontal species in this biofilm model was reproducible and could be perpetuated in vitro through several cycles. The model could be useful in future studies to characterize different periodontopathogenic properties and biofilm interactions, especially in recolonization studies.
Mol Oral Microbiol 2010 Feb
PMID:Perpetuation of subgingival biofilms in an in vitro model. 2033 96

Toll-like receptor 9 (TLR9) expression is increased in periodontally diseased tissues compared with healthy sites indicating a possible role of TLR9 and its ligand, bacterial DNA (bDNA), in periodontal disease pathology. Here, we determine the immunostimulatory effects of periodontal bDNA in human monocytic cells (THP-1). THP-1 cells were stimulated with DNA of two putative periodontal pathogens: Porphyromonas gingivalis and Tannerella forsythia. The role of TLR9 in periodontal bDNA-initiated cytokine production was determined either by blocking TLR9 signaling in THP-1 cells with chloroquine or by measuring IL-8 production and nuclear factor-kappaB (NF-kappaB) activation in HEK293 cells stably transfected with human TLR9. Cytokine production (IL-1beta, IL-6, and TNF-alpha) was increased significantly in bDNA-stimulated cells compared with controls. Chloroquine treatment of THP-1 cells decreased cytokine production, suggesting that TLR9-mediated signaling pathways are operant in the recognition of DNA from periodontal pathogens. Compared with native HEK293 cells, TLR9-transfected cells demonstrated significantly increased IL-8 production (P < 0.001) and NF-kappaB activation in response to bDNA, further confirming the role of TLR9 in periodontal bDNA recognition. The results of PCR arrays demonstrated upregulation of proinflammatory cytokine and NF-kappaB genes in response to periodontal bDNA in THP-1 cells, suggesting that cytokine induction is through NF-kappaB activation. Hence, immune responses triggered by periodontal bacterial nucleic acids may contribute to periodontal disease pathology by inducing proinflammatory cytokine production through the TLR9 signaling pathway.
Mol Oral Microbiol 2010 Apr
PMID:DNA from Porphyromonas gingivalis and Tannerella forsythia induce cytokine production in human monocytic cell lines. 2033

IL-6 is well recognized to be a potent bone resorptive agent and thus in the development of periodontal disease. Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), the major catechins in green tea, and theaflavin-3,3'-digallate (TFDG), polyphenol in black tea, have multiple beneficial effects, but the effects of catechins and theaflavins on IL-6 production in human gingival fibroblasts (HGFs) are not known. In this study, we investigated the mechanisms by which EGCG, ECG, and TFDG inhibit tumor necrosis factor superfamily 14 (TNFSF14)-induced IL-6 production in HGFs. We detected TNFSF14 mRNA expression in human diseased periodontal tissues. TNFSF14 increased IL-6 production in HGFs in a concentration-dependent manner. EGCG, ECG, and TFDG prevented TNFSF14-mediated IL-6 production in HGFs. EGCG, ECG, and TFDG prevented TNFSF14-induced extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappaB activation in HGFs. Inhibitors of ERK, JNK, and nuclear factor-kappaB decreased TNFSF14-induced IL-6 production. In addition, EGCG, ECG, and TFDG attenuated TNFSF14 receptor expression on HGFs. These data provide a novel mechanism through which the green tea and black tea polyphenols could be used to provide direct benefits in periodontal disease.
Mol Nutr Food Res 2010 Jul
PMID:Tea polyphenols inhibit IL-6 production in tumor necrosis factor superfamily 14-stimulated human gingival fibroblasts. 2046 39

Periodontal disease involves complex interactions of microorganisms and host defenses. This work investigated the associations between putative bacterial pathogens, herpesviruses and chronic periodontitis. Subgingival samples were collected from 40 periodontally healthy individuals and from 40 patients with chronic periodontitis with probing depths of < or =3 mm or > or =6 mm. Multiplex and nested polymerase chain reactions were used to identify bacterial pathogens and herpesviruses. Porphyromonas gingivalis, Tannerella forsythia, Epstein-Barr virus (EBV) type 1, cytomegalovirus (CMV), Aggregatibacter actinomycetemcomitans and EBV type 2 were detected in, respectively, 95, 75, 72.5, 50, 12.5 and 10% of sites with probing depths > or =6 mm. P. gingivalis, T. forsythia, EBV-1 and CMV were statistically associated with probing depths > or =6 mm. A. actinomycetemcomitans and EBV-2 showed no association with periodontitis sites, and no significant associations were found for any of the test infectious agents and probing depths < or =3 mm. Our results confirm an association between P. gingivalis, T. forsythia, EBV-1 and CMV, and chronic periodontitis. These infectious agents may play an important synergistic role in the pathogenesis of chronic periodontitis.
Mol Oral Microbiol 2010 Jun
PMID:Periodontopathic bacteria and herpesviruses in chronic periodontitis. 2053 51

Treponema denticola levels in the gingival crevice become elevated as periodontal disease develops. Oral treponemes may account for as much as 40% of the total bacterial population in the periodontal pocket. The stimuli that trigger enhanced growth of T. denticola, and the mechanisms associated with the transmission of these signals, remain to be defined. We hypothesize that the T. denticola open reading frames tde1970 (histidine kinase) and tde1969 (response regulator) constitute a functional two-component regulatory system that regulates, at least in part, responses to the changing environmental conditions associated with the development of periodontal disease. The results presented demonstrate that tde1970 and tde1969 are conserved, universal among T. denticola isolates and transcribed as part of a seven-gene operon in a growth-phase-dependent manner. tde1970 undergoes autophosphorylation and transfers phosphate to tde1969. Henceforth, the proteins encoded by these open reading frames are designated as Hpk2 and Rrp2 respectively. Hpk2 autophosphorylation kinetics were influenced by environmental conditions and by the presence or absence of a PAS domain. It can be concluded that Hpk2 and Rrp2 constitute a functional two-component system that contributes to environmental sensing.
Mol Oral Microbiol 2010 Aug
PMID:The Hpk2-Rrp2 two-component regulatory system of Treponema denticola: a potential regulator of environmental and adaptive responses. 2061 98

There is mounting evidence that innate and adaptive immunity are critical for periodontal disease-mediated bone resorption. These studies examined the role of B and CD4 T cells in adaptive immunity of rats infected with Aggregatibacter actinomycetemcomitans (Aa). Sprague-Dawley male rats were fed Aa-containing mash or control-mash for 2 weeks. B and CD4 T cells were obtained from draining lymph nodes at 2, 4 and 12 weeks, postinoculation. Quantitative polymerase chain reaction-based messenger RNA expression was conducted for 89 cytokine family genes. Disease-relevance of the differentially expressed genes was assessed using a biological interaction pathway analysis software. B and CD4 T cells of Aa-infected rats increased and were activated, resulting in enhanced isotype-switched serum immunoglobulin G by 2 weeks postinoculation. Bone resorption was evident 12 weeks after Aa-feeding. In B cells, interleukin-2 (IL-2), macrophage-inhibiting factor, IL-19, IL-21, tumor necrosis factor (TNF), CD40 ligand (CD40L), CD70, bone morphogenetic protein 2 (BMP2), BMP3, and BMP10 were upregulated early; while IL-7, Fas ligand (FasL), small inducible cytokine subfamily E1, and growth differentiation factor 11 (GDF11; BMP11) were upregulated late (12 weeks). BMP10 was sustained throughout. In CD4 T cells, IL-10, IL-16, TNF, lymphotoxin-beta (LTbeta), APRIL, CD40L, FasL, RANKL and osteoprotegerin were upregulated early, whereas IL-1beta, IL-1RN, IL-1F8, IL-24, interferon-alpha1, GDF11 (BMP11), and GDF15 were upregulated late (12 weeks). Adaptive immunity appears crucial for bone resorption. Several of the deregulated genes are, for the first time, shown to be associated with bone resorption, and the results indicate that activated B cells produce BMP10. The study provides a rationale for a link between periodontal disease and other systemic diseases.
Mol Oral Microbiol 2010 Aug
PMID:Adaptive immune response in osteoclastic bone resorption induced by orally administered Aggregatibacter actinomycetemcomitans in a rat model of periodontal disease. 2061 1

The development of analytical methods enabling the accurate identification and enumeration of bacterial species colonizing the oral cavity has led to the identification of a small number of bacterial pathogens that are major factors in the etiology of periodontal disease. Further, these methods also underpin more recent epidemiological analyses of the impact of periodontal disease on general health. Given the complex milieu of over 700 species of microorganisms known to exist within the complex biofilms found in the oral cavity, the identification and enumeration of oral periodontopathogens has not been an easy task. In recent years however, some of the intrinsic limitations of the more traditional microbiological analyses previously used have been overcome with the advent of immunological and molecular analytical methods. Of the plethora of methodologies reported in the literature, the enzyme-linked immunosorbent assay (ELISA), which combines the specificity of antibody with the sensitivity of simple enzyme assays and the polymerase chain reaction (PCR), has been widely utilized in both laboratory and clinical applications. Although conventional PCR does not allow quantitation of the target organism, real-time PCR (rtPCR) has the ability to detect amplicons as they accumulate in "real time" allowing subsequent quantitation. These methods enable the accurate quantitation of as few as 10(2) (using rtPCR) to 10(4) (using ELISA) periodontopathogens in dental plaque samples.
Methods Mol Biol 2010
PMID:Quantitative analysis of periodontal pathogens by ELISA and real-time polymerase chain reaction. 2071 82

Porphyromonas gingivalis is a Gram-negative anaerobic bacterium associated with the initiation and progression of adult periodontal disease. The pathogenicity of P. gingivalis is multifaceted and the infection process is influenced by both microbial and host factors. It is generally accepted that genes of a pathogen that are specifically expressed during infection are likely to be important for pathogenicity. Numerous technologies have been developed to identify these genes. A novel strategy known as in vivo-induced antigen technology (IVIAT) avoids the use of animal models and utilizes serum from patients who have experienced disease caused by the pathogen of interest. While a number of putative virulence factors have been described for P. gingivalis, the identity, relevance, and mechanisms of action of virulence factors that actually provide a selective advantage to the organism in the oral cavity of diseased patients is still unclear. Here we describe the IVIAT protocol for identification of in vivo-induced genes of P. gingivalis, which can be adapted with few modifications to any microbial pathogen.
Methods Mol Biol 2010
PMID:Use of in vivo-induced antigen technology (IVIAT) to identify virulence factors of Porphyromonas gingivalis. 2071 86

Human periodontal ligament stem cells (PDLSCs) are a unique population of mesenchymal stem cells (MSCs) which demonstrate the capacity to generate cementum- and periodontal ligament-like structures in vivo. As such, PDLSCs represent a promising cell-based therapy in reconstructive dentistry for the treatment of periodontal disease. The present chapter describes two methods for isolating PDLSCs from human PDL tissue including traditional plastic adherence and immunomagnetic selection based on the expression of MSC-associated surface markers STRO-1 antigen, CD146 (MUC-18), CD29 (integrin beta-1), CD44, and CD106 (VCAM-1). Although no single antibody demonstrates specificity for MSCs, isolation based on the expression of individual markers results in homogeneous preparations of PDLSCs. Methods to further characterize the immunophenotype and multipotent capacity of PDLSCs to differentiate into adipocytes, osteoblast- and cementoblast-like cells in vitro, and cementum- and periodontal ligament-like tissues in vivo are also described.
Methods Mol Biol 2010
PMID:A method to isolate, purify, and characterize human periodontal ligament stem cells. 2071 90

Techniques to analyze the host immune response elicited by the presence of oral microorganisms and their products are central to our understanding of the local and systemic effects of oral diseases. This immune response has been extensively investigated for periodontal disease. The local response may result in lesions involving the gingival tissues and depending upon host susceptibility and microbial virulence may lead to local tissue destruction. More recently, however, the importance of the systemic inflammatory and immune response to oral organisms has been recognized. These systemic responses have been associated with an increased risk for cardiovascular disease, diabetes, and preterm low birth weight. A number of techniques are used extensively by researchers investigating humoral and cellular immune responses to oral organisms both in local oral tissues and fluids and systemically in peripheral blood. These are enzyme-linked immunosorbent assay (ELISA) to quantify specific antibody and cytokines in serum, gingival crevicular fluid (GCF), and saliva; characterization of T cells from peripheral blood and gingival tissues using flow cytometry; and immunohistological analysis of the inflammatory cell infiltrate in gingival tissues.
Methods Mol Biol 2010
PMID:Immunological techniques: ELISA, flow cytometry, and immunohistochemistry. 2071 93


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