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

Porphyromonas gingivalis is thought to be one of the major pathogenic organisms of adult periodontitis. Of the several virulence factors associated with the pathology it causes, evidence is now presented suggesting that outer membrane vesicles, which form from blebbing of the outer membrane, may also contribute to the pathogenesis of this bacterium. To evaluate this possibility, outer membrane vesicles were isolated from cultures of P. gingivalis and tested for their ability to promote inflammation and for their effects on the biosynthesis of E-selectin and ICAM-1 adhesion molecules and MHC class II glycoproteins. The results indicate that these vesicles are capable of inducing acute inflammation characterized by the accumulation of a large number of neutrophils in the connective tissue. This cellular response corresponds to the vesicle-mediated biosynthesis and surface membrane expression of E-selectin and ICAM-1 by vascular endothelial cells. In contrast, IFN-gamma-dependent synthesis of MHC class II molecules was found to be inhibited by vesicles. Inhibition of HLA-DR expression occurred regardless of whether vesicles were added at the same time as, 24 h before, or 24 h after IFN-gamma stimulation of endothelial cells, suggesting that the inhibitory effects occur at both the membrane and intracellular level. These findings, taken together, indicate that P. gingivalis membrane vesicles are capable of inducing and regulating cellular responses involved in inflammation and initiation of acquired immunity. Membrane vesicles are composed of muramyl peptides, periplasmic proteins and outer membrane constituents. The combination of these components probably contribute to the immune regulatory functions reported herein.
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PMID:Outer membrane vesicles of Porphyromonas gingivalis inhibit IFN-gamma-mediated MHC class II expression by human vascular endothelial cells. 1045 19

The purpose of our study was to investigate the immune response in chronical periapical parodontitis (CPP) by using multidisciplinary approach. 30 CPP samples were obtained after surgical removal--apicoectomy. Each CPP sample was examined by histological, bacteriological and flow cytometrical (FC) analysis of lymphocytes infiltrating CPP samples. Ten percent of bacteriological samples were sterile, others had significant aerobic and anaerobic growth. We used pathohistologic and microbiologic findings and compared them to the results of immunological analysis. By FC we found a significant increase in proportions of T lymphocytes expressing interleukin-2 receptors and ICAM-1 compared to peripheral blood lymphocytes. Proportions of T helper cells that produce interferon-gama (IFN-gamma) was higher in CPP samples predominantly colonized by anaerobic bacteria. There were no differences in IL-4 expression by T cells in both groups (anaerobic and streptococcal). Among anaerobic CPP samples differences in proportion of T cells that express IL-2 receptors expression was also found between samples colonised by P. acnes and Bacteroides sp. Oral streptococci cause relatively limited tissue destruction and induce Th2 type of immune response accompanied by non-cytotoxic inflammatory reaction. On the contrary, anaerobic bacteria induce Th1 type of immune response that cause more severe inflammatory reaction (type 4) of hypersensitivity that damage the tissue by the action of cytotoxic T cell activation.
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PMID:Immune response in chronic periapical parodonititis. 1100 23

Periodontal disease is an infection in which destruction occurs at sites remote from the infection, resulting in pathological pocketing. Intervening between the infection and the destruction is a dense mononuclear inflammatory infiltrate. It has been suggested that this infiltrate might have characteristics and the destructive potential of Th1-type T lymphocytes. To ascertain the nature of the infiltrates we investigated the expression of mRNA for IL-2, IL-5, and IFN-gamma by gingival mononuclear cells (GMC) from healthy (n = 8) or adult periodontitis (AP) patients (n = 25) by using cytokine-specific reverse-transcription/polymerase-chain-reaction (RT-PCR). GMC, as obtained from patients' tissues, expressed IL-2, IFN-gamma, or IL-5 mRNA. Significantly higher proportions of GMC from AP patients expressed IL-2 and IFN-gamma mRNA than did those from healthy subjects. IFN-gamma was the most consistent cytokine message detected. In other experiments, gingival T-lymphocytes (n = 12) and CD4+ and CD8+ gingival T-lymphocytes (n = 16) were isolated from gingival tissues removed surgically from AP patients. AP gingival T-lymphocytes expressed mRNA for IL-2, IFN-gamma, or IL-6 prior to stimulation. After stimulation with Con A, the cells significantly up-regulated IL-5 and IL-6 message expression. Both CD4+ and CD8+ gingival T-lymphocytes expressed IFN-gamma, IL-5, and some IL-2. This cumulative cytokine profile observed in these experiments is consistent with the predominance of Th1-type cells in pathological tissues and with Th2-type cells, which can also be present, being up-regulated under appropriate stimulation. Importantly, CD4+ and CD8+ lymphocytes were shown to express T1- and T2-type cytokine message, emphasizing the potential for CD8+ T-lymphocytes to participate in periodontal disease pathology.
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PMID:Cytokine profiles of T-lymphocytes from gingival tissues with pathological pocketing. 1102 73

Accumulation and fragmentation of hyaluronic (HA) accompanies the inflammatory changes in the periodontium and gingival crevicular fluid are involved in periodontitis, but the mechanism for this is unknown. Recently, three human hyaluronan-synthase (HAS1, 2, and 3) genes have been cloned and characterised as synthesising hyaluronans of different molecular weights. Both HAS1 and HAS2 synthesise high molecular-weight HA, whereas HAS3 produces lower molecular weight HA. In the present study the regulation of HAS genes by cytokines in cultured human periodontal ligament (PDL) cells was investigated using a novel real-time fluorescence polymerase chain reaction detection system. Human PDL cells derived from premolars were cultured with or without tumour necrosing factor (TNF)-alpha (1-100 ng/ml), interleukin (IL)-1beta (0.1-10 ng/ml) and interferon (IFN)-gamma (1-100 ng/ml). Expression of HAS mRNA was assessed in cultured cells treated with these cytokines for 0-24 h. The expression of HAS2 mRNA was enhanced about 4.5- and 2.2-fold at maximum after 3-h stimulation with 10 ng/ml TNF-alpha and 1 ng/ml IL-1beta, respectively, whereas IFN-gamma exerted little effect on HAS2 or HAS3 mRNA expression during the experiment. Expression of HAS3 mRNA was increased by about 14- and 10-fold after 3-h stimulation with 10 ng/ml TNF-alpha and 1 ng/ml IL-1beta, respectively. These results suggest that TNF-alpha and IL-1beta regulate HAS expression, and consequently may result in an accumulation of HA and an increase in HA of a lower molecular-weight.
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PMID:Regulation of hyaluronan synthase gene expression in human periodontal ligament cells by tumour necrosis factor-alpha, interleukin-1beta and interferon-gamma. 1138 68

The purpose was to investigate the balance between interferon (IFN)-gamma- and interleukin (IL)-4-bearing cells in various human inflamed gingiva by immunohistochemistry. Gingival tissues obtained from patients with gingivitis or periodontitis were divided into three groups based on the degree of histopathological inflammation, mild, moderate and severe. The tissues were also divided into four groups according to the clinical probing depth (PD). IFN-gamma- and IL-4-bearing cells in gingival tissues were stained immunohistologically and counted. The ratio of IL-4-bearing cells to IFN-gamma-bearing cells was calculated for each section. IFN-gamma-bearing cells were widespread in the connective tissue and their number increased significantly with the severity of inflammation and an increase of PD. IL-4-bearing cells were located beneath the pocket epithelium and their number showed no significant differences among the inflammation or PD groups. The ratios of IL-4-bearing cells to IFN-gamma-bearing cells in the severe inflammation or deep PD groups were significantly lower than those in the moderate inflammation or shallow PD groups. These results suggest that a low ratio of IL-4-bearing cells to IFN-gamma-bearing cells might be involved in the destruction of periodontal tissue.
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PMID:Immunohistological study of interferon-gamma- and interleukin-4-bearing cells in human periodontitis gingiva. 1145 4

Numerous studies have attempted to elucidate the cytokine networks involved in chronic periodontitis, often with conflicting results. A variety of techniques were used to study cells in situ, cells extracted from gingival tissues, peripheral blood mononuclear cells, purified cell populations, and T cell lines and clones. Bacterial components, including sonicates, killed cells, outer membrane components, and purified antigens, have all been used to stimulate cells in vitro, making comparisons of cytokine profiles difficult. As it is likely that different cells are present at different disease stages, the inability to determine disease activity clinically is a major limitation of all these studies. In the Context of tissue destruction, cytokines such as IL-1, IL-6 and IL-18 are likely to be important, as are their regulating cytokines IL-10 and IL-11. In terms of the nature of the inflammatory infiltrate, two apparently conflicting hypotheses have emerged: one based on direct observations of human lesions, the other based on animal experimentation and the inability to demonstrate IL-4 mRNA in gingival extracts. In the first of these, Th1 responses are responsible for the stable lesion, while in the second Th2 responses are considered protective. Using Porphyromonas gingivalis-specific T cell lines we have shown a tendency for IFN-gamma production rather than IL-4 or IL-10 when antigen is presented with peripheral blood mononuclear cells which may contain dendritic cells. It is likely that the nature of the antigen-presenting cell is fundamental in determining the nature of the cytokine profile, which may in turn open up possibilities for new therapeutic modalities.
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PMID:Cytokines in periodontal disease: where to from here? 1150 86

Previous studies have analyzed the lymphoid and myeloid foci within the gingival mucosa in health and chronic periodontitis (CP); however, the principal APCs responsible for the formation and organizational structure of these foci in CP have not been defined. We show that in human CP tissues, CD1a(+) immature Langerhans cells predominantly infiltrate the gingival epithelium, whereas CD83(+) mature dendritic cells (DCs) specifically infiltrate the CD4(+) lymphoid-rich lamina propria. In vivo evidence shows that exacerbation of CP results in increased levels of proinflammatory cytokines that mediate DC activation/maturation, but also of counterregulatory cytokines that may prevent a Th-polarized response. Consistently, in vitro-generated monocyte-derived DCs pulsed with Porphyromonas gingivalis strain 381 or its LPS undergo maturation, up-regulate accessory molecules, and release proinflammatory (IL-1beta, PGE(2)) and Th (IL-10, IL-12) cytokines. Interestingly, the IL-10:IL-12 ratio elicited from P. gingivalis-pulsed DCs was 3-fold higher than that from Escherichia coli-pulsed DCs. This may account for the significantly (p < 0.05) lower proliferation of autologous CD4(+) T cells and reduced release of IFN-gamma elicited by P. gingivalis-pulsed DCs. Taken together, these findings suggest a previously unreported mechanism for the pathophysiology of CP, involving the activation and in situ maturation of DCs by the oral pathogen P. gingivalis, leading to release of counterregulatory cytokines and the formation of T cell-DC foci.
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PMID:Mature dendritic cells infiltrate the T cell-rich region of oral mucosa in chronic periodontitis: in situ, in vivo, and in vitro studies. 1159

IL-18, a potent IFN-gamma-inducing cytokine, is expressed by various nonimmune cells as well as macrophages, suggesting that it has important physiological and immunological roles. The present study focused on the mechanism of active IL-18 induction from human oral epithelial cells. The epithelial cells and the cell lines constitutively express IL-18 mRNA and the 24-kDa precursor form of IL-18. Bioactive IL-18 exhibiting IFN-gamma-inducing activity was detected in the supernatant of the cells on costimulation with neutrophil proteinase 3 (PR3) and LPS for 24 h after IFN-gamma-priming for 3 days. An active 18-kDa form of IL-18 was detected in lysate and supernatant of the cells only after the above treatment and the induction was inhibited by cycloheximide and by serine proteinase inhibitors. After the treatment, lactate dehydrogenase activity was not detected in the cell culture supernatant, and PR3 was detected only in the membrane and not in cytoplasm fractions of the cells. Caspase-1 was not detected in the cells even after the treatment and the IL-18 induction was not inhibited by a caspase-1 inhibitor. These results suggest that the PR3-mediated induction of bioactive IL-18 secretion from oral epithelial cells in combination with LPS after IFN-gamma-priming occurred via a caspase-1-independent pathway, and provide new insight into the possible involvement of a neutrophil proteinase in the induction of bioactive IL-18 in oral inflammation such as periodontitis.
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PMID:Neutrophil proteinase 3-mediated induction of bioactive IL-18 secretion by human oral epithelial cells. 1171 26

Heat shock protein 60s (hsp60) are remarkably immunogenic, and both T-cell and antibody responses to hsp60 have been reported in various inflammatory conditions. To clarify the role of hsp60 in T-cell responses in periodontitis, we examined the proliferative response of peripheral blood mononuclear cells (PBMC), as well as the cytokine profile and T-cell clonality, for periodontitis patients and controls following stimulation with recombinant human hsp60 and Porphyromonas gingivalis GroEL. To confirm the infiltration of hsp60-reactive T-cell clones into periodontitis lesions, nucleotide sequences within complementarity-determining region 3 of the T-cell receptor (TCR) beta-chain were compared between hsp60-reactive peripheral blood T cells and periodontitis lesion-infiltrating T cells. Periodontitis patients demonstrated significantly higher proliferative responses of PBMC to human hsp60, but not to P. gingivalis GroEL, than control subjects. The response was inhibited by anti-major histocompatibility complex class II antibodies. Analysis of the nucleotide sequences of the TCR demonstrated that human hsp60-reactive T-cell clones and periodontitis lesion-infiltrating T cells have the same receptors, suggesting that hsp60-reactive T cells accumulate in periodontitis lesions. Analysis of the cytokine profile demonstrated that hsp60-reactive PBMC produced significant levels of gamma interferon (IFN-gamma) in periodontitis patients, whereas P. gingivalis GroEL did not induce any skewing toward a type1 or type2 cytokine profile. In control subjects no significant expression of IFN-gamma or interleukin 4 was induced. These results suggest that periodontitis patients have human hsp60-reactive T cells with a type 1 cytokine profile in their peripheral blood T-cell pools.
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PMID:Accumulation of human heat shock protein 60-reactive T cells in the gingival tissues of periodontitis patients. 1195 87

Chemokines are said to be small peptides that are chemoattractants for leukocyte subpopulations within local inflammation sites. Gingival inflammation is characterized by infiltration of inflammatory mononuclear cells. The point of this study was to examine the presence or absence of chemokine-positive cells and chemokine receptor-positive cells by means of immunohistochemical methods in samples of gingival tissues obtained from patients with marginal periodontitis. Macrophage chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, (IFN-gamma)-inducible protein-10 (IP-10) and RANTES-producing cells were found to be present in inflamed human gingival tissues. In addition, CCR5- and CXCR3-positive cells were present. In contrast, no factor expression was observed in periodontally healthy gingival tissue. Our findings suggest that these chemokines may be responsible for modulating the process of infectious disease such as marginal periodontitis.
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PMID:The presence of chemokine (MCP-1, MIP-1alpha, MIP-1beta, IP-10, RANTES)-positive cells and chemokine receptor (CCR5, CXCR3)-positive cells in inflamed human gingival tissues. 1244 1


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