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)

Human serum antibody responses to antigens from a suspected oral pathogen, Actinobacillus actinomycetemcomitans (Aa), were studied. IgG and IgM isotype antibodies to four antigen preparations, sonicate antigen (SA), leukotoxin (LT), group carbohydrate (LG), and lipopolysaccharide (LPS), were determined using an ELISA. An ELISA inhibition technique was developed to show that human serum antibodies reacting with the LT, LG, or LPS materials were binding to different antigenic moieties in each preparation. Cross-sectional studies of serum IgG antibodies showed that patients with localized juvenile periodontitis (LJP) had a greater frequency of occurrence and a higher level of antibodies to the SA (82%), LT (70%), and LG (62%) antigens compared to all other diseased (11-46%) or normal (4-13%) groups. Serum IgM antibodies to LPS were increased in LJP, generalized juvenile periodontitis, and adult periodontitis patients compared to all other groups. Therefore, while both IgG and IgM antibodies were found against various Aa antigens, the detection of IgG antibodies was most clearly associated with the specific disease classification of LJP. Blocking studies suggested that the human serum responses were specific for the Aa antigens and that the LT, LG, and LPS comprise major antigenic determinants on the organisms to which human serum antibody reacts.
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PMID:Human immune responses to oral microorganisms. II. Serum antibody responses to antigens from Actinobacillus actinomycetemcomitans and the correlation with localized juvenile periodontitis. 619 23

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.
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PMID:Priming effect of Porphyromonas gingivalis lipopolysaccharide on superoxide production by neutrophils from healthy and rapidly progressive periodontitis subjects. 815 9

Chronic inflammatory reactions are usually characterized by inflammatory cell accumulation in the extravascular connective tissue. In such sites, inappropriate activation of circulating or resident lymphocytes becomes self-perpetuating and can lead to chronic tissue destruction. In addition to that, the locally infiltrated lymphocytes should have an opportunity to interact directly with fibroblasts composing the connective tissue. The direct interactions of those different cell types seem to play important roles in lymphocyte lodging and retention in such sites. Thus, for clarification of the immunopathogenesis of the chronic inflammatory diseases, including periodontitis, it is important that the molecular mechanisms involved in the heterotypic cell-cell interactions be revealed. In fact, it has been demonstrated that lymphocytes interact with various non-hematopoietic cells, such as epithelial cells and endothelial cells. Regarding interactions with fibroblasts, it has been shown that IFN gamma-stimulated fibroblasts can regulate the proliferative responses of T-lymphocytes both positively and negatively. Furthermore, activated lymphocytes have demonstrated strong binding ability to various fibroblast cell lines. Blocking experiments utilizing monoclonal antibodies specific to various cell adhesion molecules revealed that very late antigen (VLA) integrins, lymphocyte-function-associated antigen (LFA-1)/intercellular adhesion molecule-1 (ICAM-I), CD44/hyarulonate are, at least in part, involved in lymphocyte-fibroblast interactions. In addition, recent findings raised the possibility that the adhesive interactions between lymphocytes and fibroblasts influenced the various cellular functions of each cell type. In fact, it was recently demonstrated that the adhesive interactions stimulated fibroblasts to increase expression of inflammatory cytokine mRNA. These results strongly suggest that fibroblasts are not merely innocent bystanders but actively participate in local inflammatory reactions by directly interacting with locally infiltrated lymphocytes.
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PMID:Lymphocyte-fibroblast interactions. 906 24

Monoclonal antibody (MAb) 61BG1.3 prevented recolonization of deep pockets by Porphyromonas gingivalis in patients with periodontitis. The aim of this work was to identify the antigen recognized by the MAb. This was carried out by dose-dependent inhibition with materials extracted from P. gingivalis and assessed by a radioimmunoassay. A protease preparation and a capsular extract inhibited about 95% of the binding activity, whereas LPS or fimbriae had no effect. However, about 125 times greater concentration of the capsular than the protease material was needed to inhibit 50% of the antibody activity, suggesting that the MAb recognizes the protease preparation and that the capsular extract contained some protease. Western blotting of MAb 61BG1.3 with recombinant prpR1 protein expressed in Escherichia coli confirmed that MAb 61BG1.3 recognizes the haemagglutinating protease and mapped its epitope to residues 748-1130 of the beta component of the polyprotein. Three major bands of M(r) 45,000, 38,300 and 31,400 were detected in native whole cells of the virulent P. gingivalis strain W50 by Western blotting with MAb 61BG1.3. The MAb inhibited haemagglutination of human red blood cells by P. gingivalis or by a native protease extract. Blocking adhesion of P. gingivalis to the receptors on erythrocytes might be a mechanism by which the MAb inhibits recolonization by the microorganism.
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PMID:Characterization of the Porphyromonas gingivalis antigen recognized by a monoclonal antibody which prevents colonization by the organism. 908 43

Bacteria or their products may cause chronic inflammation and subsequent bone loss. This inflammation and bone loss may be associated with significant morbidity in chronic otitis media, periodontitis, endodontic lesions, and loosening of orthopedic implants caused by lipopolysaccharide (LPS)-contaminated implant particles. Currently, it is not clear how bacteria or endotoxin-induced bone resorption occurs and what cell types are involved. Here we report that Porphyromonas gingivalis, a periodontal pathogen, and Escherichia coli LPS induce osteoclastic cell formation from murine leukocytes in the absence of osteoblasts. In contrast, stimulation with parathyroid hormone had no effect. These multinucleated, tartrate-resistant acid phosphatase-positive cells were positive for receptor activator of NF-kappaB (RANK), the receptor for osteoprotegerin ligand (OPGL), also known as RANK ligand (RANKL). Blocking antibodies demonstrated that their formation was dependent upon expression of OPGL and, to a lesser extent, on tumor necrosis factor alpha. Mononuclear cells represented a significant source of OPGL production. In vivo, P. gingivalis injection stimulated OPGL expression in both mononuclear leukocytes and osteoblastic cells. Thus, these findings describe a pathway by which bacteria could enhance osteolysis independently of osteoblasts and suggest that the mix of cells that participate in inflammatory and physiologic bone resorption may be different. This may give insight into new targets of therapeutic intervention.
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PMID:Bacteria induce osteoclastogenesis via an osteoblast-independent pathway. 1201 Oct 8

Actinobacillus actinomycetemcomitans plays a major role in the pathogenesis of aggressive periodontitis. Lipopolysaccharide (LPS) derived from A. actinomycetemcomitans is a key factor in inflammatory cytokine generation within periodontal tissues. In this study, we identify major mitogen-activated protein kinase (MAPK) signaling pathways induced by A. actinomycetemcomitans LPS, Escherichia coli LPS and interleukin-1beta (IL-1beta) in a murine periodontal ligament (mPDL) fibroblast cell line. Immunoblot analysis was used to assess the phosphorylated forms of p38, extracellular-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) MAPK following stimulation with A. actinomycetemcomitans LPS, E. coli LPS and IL-1beta. IL-6 mRNA induction was detected via reverse transcription-polymerase chain reaction, while protein levels were quantified via enzyme-linked immunosorbent assays (ELISA). We utilized biochemical inhibitors of p38, ERK and JNK MAPK to identify the MAPK signaling pathways needed for IL-6 expression. Additional use of stable mPDL cell lines containing dominant negative mutant constructs of MAPK kinase-3 and -6 (MKK-3/6) and p38 null mutant mouse embryonic fibroblast (MEF) cells were used to substantiate the biochemical inhibitor data. Blocking p38 MAPK with SB203580 reduced the induction of IL-6 mRNA by A. actinomycetemcomitans LPS, E. coli LPS and IL-1beta by >70%, >95% and approximately 60%, respectively. IL-6 ELISA indicated that blocking p38 MAPK reduced the IL-6 protein levels induced by A. actinomycetemcomitans LPS, E. coli LPS and IL-1beta by approximately 60%, approximately 50% and approximately 70%, respectively. All MAPK inhibitors significantly reduced the IL-6 protein levels induced by A. actinomycetemcomitans LPS, E. coli LPS and IL-1beta whereas only p38 inhibitors consistently reduced the A. actinomycetemcomitans LPS, E. coli LPS and IL-1beta induction of IL-6 mRNA steady-state levels. The contribution of p38 MAPK LPS-induced IL-6 expression was confirmed using MKK-3/6 dominant negative stable mPDL cell lines. Wild-type and p38alpha(-/-) MEF cells provided additional evidence to support the role of p38alpha MAPK in A. actinomycetemcomitans LPS-stimulated IL-6. Our results indicate that induction of IL-6 by E. coli LPS, IL-1beta and A. actinomycetemcomitans LPS requires signaling through MKK-3-p38alpha ERK, JNK and p38 MAPK in mPDL cells.
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PMID:Actinobacillus actinomycetemcomitans lipopolysaccharide induces interleukin-6 expression through multiple mitogen-activated protein kinase pathways in periodontal ligament fibroblasts. 1706 98

CXCL8 (interlukin 8, IL-8) has a diverse spectrum of biological activities including T cell, neutrophil and basophil chemotactic properties. It is produced by a wide variety of cell types and plays a significant role in the initiation of the acute inflammatory response. During inflammation, CXCL8 attracts and activates leukocytes at the site of infection leading to leukocyte infiltration, which can lead to tissue damage. Porphyromonas gingivalis, an aetiological agent of periodontitis, induces production of CXCL8 from several types of cells via its LPS and outer membrane proteins. Bacterial chaperones elicit a strong pro-inflammatory response in cells of the innate immune system. In P. gingivalis the htpG gene codes for the homologue of human Hsp90, a chaperone that associates with transcription factors, hormone receptors and protein kinases, affecting signal transduction pathways. CXCL8 mRNA and CXCL8 protein production was induced in monocytic/human microvascular vein endothelial cells treated with P. gingivalis cells or rHtpG protein. Blocking of receptors CD91 and TLR4 reduced the production of CXCL8 by rHtpG either using receptor-specific antibody or by siRNA silencing. Pre-incubation of P. gingivalis rHtpG preparations with human anti-HtpG significantly inhibited CXCL8 production. A P. gingivalis HtpG disruption mutant also induced less CXCL8 mRNA and protein. These results suggest that P. gingivalis HtpG might be involved in CXCL8-mediated immunopathogenesis.
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PMID:HtpG, the Porphyromonas gingivalis HSP-90 homologue, induces the chemokine CXCL8 in human monocytic and microvascular vein endothelial cells. 1734 15

Diphenylhydantoin (DPH) is widely used as an anticonvulsant drug. We examined the effects of DPH on osteoclast differentiation and function using in vivo and in vitro assay systems. Transgenic mice overexpressing a soluble form of RANKL (RANKL Tg) exhibited increased osteoclastic bone resorption. Injection of DPH into the subcutaneous tissue overlying calvaria of RANKL Tg mice suppressed the enhanced resorption in the calvaria. In co-cultures of mouse osteoblasts and bone marrow cells, DPH inhibited lipopolysaccharide (LPS)-induced osteoclast formation. DPH affected neither the mRNA expression of RANKL and osteoprotegerin nor the growth of mouse osteoblasts in culture. On the other hand, DPH inhibited the RANKL-induced formation of osteoclasts in cultures of mouse bone marrow-derived macrophages (BMMphis) and of human peripheral blood-derived CD14(+) cells. DPH concealed LPS-induced bone resorption in mouse calvarial organ cultures and inhibited the pit-forming activity of mouse osteoclasts cultured on dentine slices. DPH suppressed the RANKL-induced calcium oscillation and expression of nuclear factor of activated T cells c1 (NFATc1) and c-fos in BMMphis. Moreover, DPH inhibited the RANKL-induced nuclear localization and auto-amplification of NFATc1 in mature osteoclasts. Both BMMphis and osteoclasts expressed mRNA of a T-type calcium channel, Cav3.2, a target of DPH. Blocking the expression of Cav3.2 by short hairpin RNAs significantly suppressed RANKL-induced osteoclast differentiation. These results suggest that DPH inhibits osteoclast differentiation and function through suppression of NFATc1 signaling. The topical application of DPH may be a therapeutic treatment to prevent bone loss induced by local inflammation such as periodontitis.
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PMID:Diphenylhydantoin inhibits osteoclast differentiation and function through suppression of NFATc1 signaling. 1929 14

Chronic periodontitis is an inflammatory disease affecting periodontal connective tissues and alveolar bone. Proinflammatory mediators induced by periodontal pathogens play vital roles in the initiation and progression of the disease. In this study, we examined whether Prevotella intermedia induces proinflammatory cytokines expression in human periodontal ligament cells (hPDLs). The mRNA expression and protein production were determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbant assay (ELISA) respectively. P. intermedia treatment dose- and time-dependently increased IL-6, IL-8 and M-CSF, but not IL-1beta and TNF-alpha mRNA expression and protein secretion. Preincubation of hPDLs with extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 kinase and phosphatidylinositol 3-kinase (PI3K) inhibitors PD98059, SP600125, SB203580 and LY294002 resulted in significant reduction in P. intermedia-induced IL-6, IL-8 and M-CSF expression. Blocking the synthesis of prostaglandin E(2) (PGE(2)) by indomethacin also abolished the stimulatory effects of P. intermedia on cytokines expression. Our results indicate that P. intermedia induces proinflammatory cytokines through MAPKs and PI3K signaling pathways, and PGE(2) is involved in the P. intermedia-induced proinflammatory cytokines upregulation.
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PMID:Mitogen-activated protein kinases and phosphatidylinositol 3-kinase are involved in Prevotella intermedia-induced proinflammatory cytokines expression in human periodontal ligament cells. 1953 37

Halitosis (bad breath) is estimated to influence more than half of the world's population with varying degree of intensity. More than 85% of halitosis originates from oral bacterial infections. Foul-smelling breath mainly results from bacterial production of volatile sulfur compounds (VSCs) such as hydrogen sulfide and methyl mercaptan. To date, major treatments for elimination of oral malodor include periodontal therapy combined with antibiotics or antimicrobial agents, and mechanical approaches including tooth and tongue cleaning. These treatments may transiently reduce VSCs but carry risks of generating toxicity, increasing resistant strains and misbalancing the resident human flora. Therefore, there is a need to develop alternative therapeutic modalities for halitosis. Plaque biofilms are the principal source for generating VSCs which are originally metabolized from amino acids during co-aggregation of oral bacteria. Blocking the bacterial coaggregation, therefore, may prevent various biofilm-associated oral diseases such as periodontitis and halitosis. Fusobacterium nucleatum (F. nucleatum), a Gram-negative anaerobe oral bacterium, is a main bacterial strain related to halitosis. Aggregation of F. nucleatum with other bacteria to form plaque biofilms in oral cavity causes bad breath. FomA, the major outer membrane protein of F. nucleatum, recruits other oral pathogenic bacteria such as Porphyromonas gingivalis (P. gingivalis) in the periodontal pockets. A halitosis vaccine targeting F. bacterium FomA significantly abrogates the enhancement of bacterial co-aggregation, biofilms, production of VSCs, and gum inflammation mediated by an inter-species interaction of F. nucleatum with P. gingivalis, which suggests FomA of F. nucleatum to be a potential target for development of vaccines or drugs against bacterial biofilm formation and its associated pathogenicities.
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PMID:Halitosis vaccines targeting FomA, a biofilm-bridging protein of fusobacteria nucleatum. 2386 30


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