Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pre-incubation of neutrophils from rapidly progressive periodontitis (RPP) patients with lipopolysaccharide (LPS) extracted from Porphyromonas gingivalis was found to prime the neutrophils for enhanced FMLP-stimulated superoxide production in a dose-dependent manner. The priming effect of P. gingivalis LPS on neutrophils from control subjects was scanty or without effect at all. Inclusion of human serum in the experimental priming conditions increased the control and RPP neutrophil response by 2 to 3 fold. Blocking of the CD14 receptor on the neutrophil surface with monoclonal antibody eliminated the priming effect. Furthermore, incubation of control neutrophils with P. gingivalis LPS in the presence of serum from RPP patients generated a higher response as compared to incubation with control serum. The data suggest that neutrophil priming described in RPP patients is dependent on a serum factor which alters the neutrophil response to priming agents such as LPS.
 ...
PMID:Priming effect of Porphyromonas gingivalis lipopolysaccharide on superoxide production by neutrophils from healthy and rapidly progressive periodontitis subjects. 815 9

Normal bone remodelling requires the coordinated regulation of the genesis and activity of osteoblast and osteoclast lineages. Any interference with these integrated cellular systems can result in dysregulation of remodelling with the consequent loss of bone matrix. Bacteria are important causes of bone pathology in common conditions such as periodontitis, dental cysts, bacterial arthritis, and osteomyelitis. It is now established that many of the bacteria implicated in bone diseases contain or produce molecules with potent effects on bone cells. Some of these molecules, such as components of the gram-positive cell walls (lipoteichoic acids), are weak stimulators of bone resorption in vitro, while others (PMT, cpn60) are as active as the most active mammalian osteolytic factors such as cytokines like IL-1 and TNF. The complexity of the integration of bone cell lineage development means that there are still question marks over the mechanism of action of many well-known bone-modulatory molecules such as parathyroid hormone. The key questions which must be asked of the now-recognized bacterial bone-modulatory molecules are as follows: (i) what cell population do they bind to, (ii) what is the nature of the receptor and postreceptor events, and (iii) is their action direct or dependent on the induction of secondary extracellular bone-modulating factors such as cytokines, eicosanoids, etc. In the case of LPS, this ubiquitous gram-negative polymer probably binds to osteoblasts or other cells in bone through the CD14 receptor and stimulates them to release cytokines and eicosanoids which then induce the recruitment and activation of osteoclasts. This explains the inhibitor effects of nonsteroidal and anticytokine agents on LPS-induced bone resorption. However, other bacterial factors such as the potent toxin PMT may act by blocking the normal maturation pathway of the osteoblast lineage, thus inducing dysregulation in the tightly regulated process of resorption and replacement of bone matrix. At the present time, it is not possible to define a general mechanism by which bacteria promote loss of bone matrix. Many bacteria are capable of stimulating bone matrix loss, and the information available would suggest that each organism possesses different factors which interact with bone in different ways. With the rapid increase in antibiotic resistance, particularly with Staphylococcus aureus and M. tuberculosis, organisms responsible for much bone pathology in developed countries only two generations ago, we would urge that much greater attention should be focused on the problem of bacterially induced bone remodelling in order to define pathogenetic mechanisms which could be therapeutic targets for the development of new treatment modalities.
 ...
PMID:Bacterially induced bone destruction: mechanisms and misconceptions. 869 54

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.
 ...
PMID:Soluble CD14 mediates lipopolysaccharide-induced intercellular adhesion molecule 1 expression in cultured human gingival fibroblasts. 894 31

We report the evidence for apoptosis in J774.1 cells by the periodontopathic bacterium Actinobacillus actinomycetemcomitans, suggesting that the ability of A. actinomycetemcomitans to promote apoptosis might be important in the initiation and development of periodontitis. In this study, we examined the role of macrophage CD14, anchored by a glycerophosphatidylinositol tail, in the induction of apoptosis by A. actinomycetemcomitans infection by using the parent J774.1 cells and CD14-defective mutant (LR-9) cells. A small number of A. actinomycetemcomitans Y4 cells inside the LR-9 cells compared with the number in J774.1 cells was detected by confocal scanning microscopy. We found that LR-9 cells showed a weak cytotoxic effect after being infected with A. actinomycetemcomitans Y4. Apoptotic cell death of LR-9 cells infected with A. actinomycetemcomitans Y4, compared with that of the parent J774.1 cells was almost undetectable, as shown by the proportion of fragmented DNA in agarose gel electrophoresis and by the terminal deoxynucleotidyl transferase-mediated dUTP end-labeling method. Flow cytometric cell cycle analysis of J774.1 cells infected with A. actinomycetemcomitans Y4 revealed the increased percentage of apoptotic cells with hypodiploid DNA. However, LR-9 cells infected with A. actinomycetemcomitans Y4 showed no increase in population of apoptotic nuclei compared with the noninfected cells. These findings suggest that the CD14 molecules may contribute to the phagocytosis of A. actinomycetemcomitans by J774.1 cells and regulate, at least in part, apoptotic cell death of macrophages infected with A. actinomycetemcomitans.
 ...
PMID:Role of CD14 molecules in internalization of Actinobacillus actinomycetemcomitans by macrophages and subsequent induction of apoptosis. 911 44

In an attempt to clarify the immunobiological events featuring periodontitis lesions of AIDS patients in the late stage of the disease, peripheral blood (PB) and gingival crevicular fluid (GCF) leucocytes from periodontitis lesions of 23 late-stage AIDS patients were analysed by three-colour flow cytometry for detection and identification of intracytoplasmic p24+ cell fractions. The cells were reacted with CD14 and CD68 for mononuclear phagocytes or with CD4 and CD14 for Th cells, then with anti-p24 MoAb. To detect HIV proviral sequences and intracellular p24 RNA sequences, genomic DNA and cellular RNA from leucocytes were extracted for semi-nested polymerase chain reaction (PCR) amplification. CD68+/p24+ and CD14+/CD68+/p24+ fractions were larger in GCF than in PB (P<0.0001; P < 0.003). CD14+/p24+ fraction was lower in GCF than in PB (P < 0.05). The fluorescence intensities (FI) for intracellular p24 in CD68+ and CD14+/CD68+ cells were higher in GCF than in PB (P < 0.003; P < 0.02), whereas those of CD14+ macrophages did not differ. The p24 FI of CD68+ macrophages in GCF correlated with CD4+ lymphocyte counts in PB (P < 0.005). p24 FI levels of CD14+ monocytes in GCF and PB significantly correlated (P < 0.02), whereas that of CD68+ macrophages did not. PCR and reverse transcriptase (RT)-PCR of cellular DNA and RNA yielded positive signals, demonstrating viral integration and production in GCF leucocytes. These results show that periodontitis lesions in AIDS patients can be characterized by a rapid macrophage turnover, and these HIV-infected macrophage exudates in GCF may be considered as a within-mouth source of virus.
 ...
PMID:Characterization of HIV-related periodontitis in AIDS patients: HIV-infected macrophage exudate in gingival crevicular fluid as a hallmark of distinctive etiology. 915 94

The mononuclear phagocyte plays an important role in the regulation of microbe-induced inflammation, in part through its ability to secrete mediators, particularly cytokines, in response to microorganisms and their products. To evaluate the effects of the microbial flora associated with chronic adult periodontitis on cytokine induction, lipopolysaccharide (LPS) from the periodontopathogen Porphyromonas gingivalis was used to stimulate naive and phorbol ester-primed U937 monocytic cells, as well as elutriated human peripheral blood monocytes. We assessed the effect of this LPS, in comparison to that of LPS from Escherichia coli, on cell proliferation, cytokine induction, and surface expression of the LPS receptor CD14. P. gingivalis LPS stimulated proliferation of U937 cells at concentrations of greater than 1 ng/ml, while E. coli LPS inhibited proliferation. Phorbol myristic acid (PMA)-treated U937 cells and elutriated monocytes responded to E. coli LPS activation by producing tumor necrosis factor alpha (TNF-alpha) mRNA and protein; however, P. gingivalis LPS induced greater numbers of TNF-alpha mRNA-positive cells and higher (P < 0.05) levels of protein than did E. coli LPS. Both cell types expressed interleukin-1 beta (IL-1beta) mRNA and protein in response to either LPS treatment. Compared with E. coli LPS, P. gingivalis LPS induced significantly (P < 0.05) higher numbers of IL-1 mRNA-positive U937 cells and elutriated monocytes, as well as production of significantly more (P < 0.05) IL-1 protein by the monocytes. The PMA-treated U937 cells and the monocytes produced high levels of IL-1 receptor antagonist mRNA and protein which were only marginally affected by the LPS preparations. While E. coli LPS induced expression of CD 14 on the surface of PMA-primed U937 cells and monocytes, P. gingivalis LPS exhibited a significantly (P < 0.05) greater ability to enhance receptor levels. Our results indicate that P. gingivalis LPS can activate the mononuclear phagocyte for proliferation, cytokine production, and CD14 expression, providing evidence for the potential of this bacterial component to act as a critical regulatory factor in the chronic inflammatory response associated with periodontitis.
 ...
PMID:Effects of Porphyromonas gingivalis and Escherichia coli lipopolysaccharides on mononuclear phagocytes. 923 82

Early-onset periodontitis (EOP) is characterized by rapidly progressive alveolar bone loss, chemotactic defects of neutrophils, and significant familial aggregation. We found immature myeloid lineage cells, defined as promyelocytes, in the peripheral blood in patients with EOP. A hematological examination of peripheral blood cells showed normal reference values regarding cell proportions. Flow cytometry revealed significantly lower expression of CD16, a glycosylphosphatidylinositol (GPI)-anchored protein, on peripheral neutrophils in patients compared with those in age- and sex-matched healthy controls, whereas the levels of CD11a and CD11b expression were similar. The chemotactic response of neutrophils was lower toward not only formyl-methionyl-leucyl-phenylalanine but also complement fragment C5a than that of healthy controls. The expression of another GPI-anchored protein, CD14, was equally expressed by controls and patients. Therefore, the low level of CD16 expression was not due to the incomplete synthesis of the GPI anchor. GPI anchors of CD16 on neutrophils from controls and patients were both partially resistant to phosphatidylinositol-specific phospholipase C. The presence of promyelocytes in peripheral blood, low expression of CD16, and low chemotactic response of neutrophils suggest that patients with EOP have an abnormal maturation system in myeloid lineage cells in the bone marrow, which may be associated with the onset and course of EOP.
 ...
PMID:Circulating promyelocytes and low levels of CD16 expression on polymorphonuclear leukocytes accompany early-onset periodontitis. 928 70

Chronic inflammation induced by bacteria often leads to host-mediated destruction of tissues adjacent to the sites of microbial insult. The chronic inflammatory process of adult periodontitis results in the destruction of supporting osseous and connective tissues of the teeth. We hypothesized that virulence factors of periodontal pathogens such as lipopolysaccharide stimulate inflammatory cytokine expression by mononuclear cells of the host which contribute to disease development. In this study, to elucidate the role of these cytokines in chronic adult periodontitis, we tested whether the prevalence of mRNA for inflammatory cytokines generally associated with mononuclear phagocytes was higher in diseased than in healthy gingival tissue. Gingival mononuclear cells or whole gingival biopsies from 32 adult periodontitis patients and five healthy individuals used as controls were evaluated for inflammatory cytokine mRNA expression by reverse-transcription polymerase chain-reaction (RT-PCR) procedures. The cytokines assessed included IL-1 alpha, IL-1 beta, IL-1ra, IL-6, IL-8, IL-12, IL-13, TNF-alpha, TGF-beta, and IFN-gamma. The monocyte/macrophage lipopolysaccharide (LPS) receptor CD14 was also assessed. Results showed that TNF-alpha mRNA was present significantly more frequently in diseased than in healthy biopsies, whereas IL-1 alpha, IL-1 beta, and IL-1ra mRNA were found in most (from 80 to 100%) healthy tissues. Message for CD14 was present in both healthy and diseased tissue samples (100%). This study provides evidence for a major role of TNF-alpha in chronic adult periodontitis. Moreover, our results suggest that the mononuclear cells derived from periodontal tissues have the capacity to respond to components of periodontal pathogens and express both pro- and anti-inflammatory cytokines in these tissues.
 ...
PMID:Profile of cytokine mRNA expression in chronic adult periodontitis. 939 Apr 76

Adult periodontitis is a chronic destructive disease characterized by an interaction between gram-negative bacteria and the host inflammatory response. Microbial substances such as lipopolysaccharide can activate host cells, e.g., macrophages, fibroblasts and keratinocytes, to secrete proinflammatory cytokines including tumor necrosis factor alpha and interleukin 1 beta (IL-1 beta). This study examined the hypothesis that periodontitis tissue contains increased levels of cytokines that promote osseous and connective tissue destruction. To test this hypothesis, diseased and healthy gingival biopsies were examined for differences in the expression of cytokine mRNA for the pro-inflammatory cytokines tumor necrosis factor alpha and IL-1 beta and the anti-inflammatory cytokine IL-1ra using quantitative reverse transcriptase polymerase chain reaction and in situ hybridization methods. The levels of tumor necrosis factor alpha and IL-1ra mRNA were shown to be significantly higher in diseased than healthy tissues. Additionally, a significantly correlated expression of IL-1 beta and IL-1ra mRNA was seen in all tissue examined. Analysis of tissue sections by immunohistochemical and in situ hybridization techniques revealed a mononuclear cell infiltrate that consisted of a higher average number of cells staining positive for tumor necrosis factor alpha mRNA, CD14, and CD3 in the diseased than healthy tissues. Although both diseased and healthy tissues expressed IL-1 beta and IL-1ra mRNA in the epithelium, the diseased tissue biopsies expressed more IL-1 beta and IL-1ra mRNA in the connective tissue. These results implicate the potential involvement of both the pro- and anti-inflammatory cytokines in the regulation of the chronic inflammatory disease adult periodontitis.
 ...
PMID:Quantitative assessment of inflammatory cytokine gene expression in chronic adult periodontitis. 957 7

DNA binding activity of NF-kappa B and AP-1 were examined in neutrophils stimulated with LPS purified from P. gingivalis, a major pathogenic bacteria of periodontitis lesion. Porphyromonas gingivalis LPS enhanced the activity reaching a peak at a concentration of 500 ng/ml in the absence of serum. The NF-kappa B activation stimulated with 10 ng/ml of P. gingivalis LPS was suppressed approximately 44% by treatment of neutrophils with anti-CD14 antibody under the presence of serum. Increase in the steady-state IL-8 mRNA level was concomitantly observed by stimulation of neutrophils with 500 ng/ml of P. gingivalis LPS under the absence of serum. These results indicate that P. gingivalis LPS activates NF-kappa B and AP-1 in both serum-dependent and -independent manners, followed by increased IL-8 transcription in neutrophils, and suggested a role for P. gingivalis LPS in IL-8 synthesis by neutrophils in inflamed gingiva and GCF.
 ...
PMID:Activation of transcription factors and IL-8 expression in neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis. 960 13


1 2 3 4 5 6 7 Next >>