Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the role of T cell subgroups, Th1 and Th2, in the development of periodontitis, the expression of various cytokines was investigated in a mouse model of alveolar bone resorption using in situ hybridization (ISH) with digoxigenin-labeled oligonucleotides. When mice received repetitive injections with Escherichia coli lipopolysaccharide into the gingiva every 48 h, alveolar bone resorption was detectable after the fourth injection, reaching a maximum after the 13th injection. For the best performance of ISH, we first had to choose a decalcification protocol. Among various decalcification protocols, 10% EDTA (4 degrees C, 5-6 days) was the best for 28S rRNA staining. Positive cells for transcripts of interferon-gamma (Th1 product) were detected after the fourth injection, reaching a maximum after the tenth injection. A similar pattern was obtained for interleukin (IL)-10 mRNA (Th2 product) and IL-1beta, while the positive cell number reached a maximum after the 13th and 10th injections, respectively. The number of IL-4 mRNA (Th2 product)-positive cells remained low till the tenth injection, but increased thereafter. Consequently, we found that the population change from Th1 to Th2 in the inflammation site correlated with the transition from gingivitis to periodontitis, indicating differential roles of T cell subgroups in the development of periodontitis.
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PMID:Differential expression of IFN-gamma, IL-4, IL-10, and IL-1beta mRNAs in decalcified tissue sections of mouse lipopolysaccharide-induced periodontitis mandibles assessed by in situ hybridization. 956 83

Although Porphyromonas gingivalis is a defined pathogen in periodontal disease, many subjects control the infection without experiencing loss of attachment. Differences in host susceptibility to the disease may be reflected in the pattern of humoral antibodies against specific P. gingivalis antigens. The aim of this study was to determine the presence of antibodies against immunodominant P. gingivalis antigens as well as the isotype and subclass of anti-P. gingivalis antibodies against outer membrane antigens in four groups of patients: P. gingivalis-positive, 1) with and 2) without periodontitis, and P. gingivalis-negative, 3) with and 4) without periodontitis. Antigens of molecular weight 92, 63, and 32 kDa and lipopolysaccharide were found to be immunodominant. Group 1 subjects showed a significantly higher response to the 92 and 63 kDa antigens compared with other groups. The response to lipopolysaccharide was significantly higher in group 1, and lower in group 4 than in groups 2, 3. Immunoglobulin G1 (IgG1), IgG2 and IgM antibodies against P. gingivalis outer membrane were present in all subjects, while only some subjects were seropositive for IgG3, IgG4 and IgA. There were no differences in concentrations for IgG1, IgG3 and IgM. The IgG2 concentration in group 4 was significantly higher than in groups 1 and 2, while the IgG4 concentration in group 4 was significantly lower than in other groups. The frequency of seropositivity for IgG4 and IgA was lowest in group 4, while IgG3 seropositivity was almost exclusively seen in healthy patients in groups 2, 4. These findings suggest that the presence of IgG3 may reflect non-susceptibility to the disease, while lack of IgG4 may be indicative of periodontal health and lack of infection.
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PMID:Characterization of serum antibodies to Porphyromonas gingivalis in individuals with and without periodontitis. 957 96

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.
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PMID:Quantitative assessment of inflammatory cytokine gene expression in chronic adult periodontitis. 957 7

To determine if nitric oxide (NO) is produced by chronically infected human polymorphonuclear leucocytes (PMNs) in vivo, inflamed exudates (periapical exudates: PE) collected from periapical periodontitis patients were examined. Cell-free supernatants and cells were separated by centrifugation. Significant levels of nitrite concentrations were observed in the supernatants. The production of inducible NO synthase (iNOS) in highly purified PMNs derived from PEs was then immunocytochemically determined using rabbit anti-human iNOS antiserum. In vitro, human peripheral blood PMNs (PB-PMNs) isolated from patients were cultured with a combination of Esherichia coli-lipopolysaccharide (LPS), recombinant human interferon-gamma (rhIFN-gamma) and/or interleukin-1 beta (rhIL-1 beta). The stimulated PB-PMNs showed steady-state levels of nitrite. The stimulation of LPS, rhIFN-gamma and rhIL-1 beta showed more NO induction than that of LPS with either IFN-gamma or IL-1 beta, suggesting the synergistic effects of cytokines. Cryostat sections of surgically removed periapical tissues were also immunohistochemically examined for iNOS, IFN-gamma and IL-1 beta. Two-colour immunohistochemistry revealed the interaction of iNOS-producing PMNs and IFN-gamma- or IL-1 beta-producing mononuclear cells. On the basis of these data, we concluded that with the stimulation of inflammatory cytokines derived from mononuclear cells, PMNs can spontaneously produce NO at the site of chronic infection. The present studies are consistent with a hypothesis suggesting that PMNs could be regulated and delicately balanced to produce NO by mononuclear cell-derived cytokines in vivo. NO-producing cells may play a pivotal role in chronic inflammation.
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PMID:Cytokine regulation on the synthesis of nitric oxide in vivo by chronically infected human polymorphonuclear leucocytes. 961 79

We have earlier reported a higher Fcgamma-receptor (FcgammaR)-mediated generation of reactive oxygen species, measured as luminol-enhanced chemiluminescence (CL) from peripheral neutrophils in adult periodontitis patients. The aims of this study were to confirm our previous results and to elucidate the mechanism of this phenomenon by measuring CL in parallel with the intracellular production of hydrogen peroxide, after stimulation with opsonized bacteria. To determine whether the higher CL was associated with altered responsiveness to priming, the cells were preincubated with tumor necrosis factor alpha (TNFalpha) and lipopolysaccharide (LPS). While CL was significantly higher in subjects with periodontitis, there was no difference in hydrogen peroxide production between the patients and the controls, indicating that the hyperreactivity is related to the generation of other oxygen species than H2O2 and/or to processes in the outer cell membrane. The responsiveness to priming with LPS on CL was slightly but not significantly higher in the periodontitis group, suggesting that priming could be of value for distinguishing subjects with periodontitis. When assaying intracellular production of H2O2, TNFalpha and LPS had both a priming and an activating effect. There were no significant differences between the two groups. In conclusion, this study shows a higher FcgammaR-mediated CL of peripheral neutrophils from adult patients with periodontitis, thus confirming our earlier results. The hyperreactivity seems to be related to the outer cell membrane or to oxygen species other than H2O2.
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PMID:Hyper-reactive peripheral neutrophils in adult periodontitis: generation of chemiluminescence and intracellular hydrogen peroxide after in vitro priming and FcgammaR-stimulation. 965 Aug 76

Based upon the prosthodontic literature, subjects who are at the transition stage between natural dentition and edentulism are called "terminal dentition" (TD) cases. The aim of the present cross-sectional investigation was to characterize the local and systemic inflammatory responses in 2 groups of patients with terminal dentition periodontitis. Eight severe adult periodontitis terminal dentition (AP-TD) subjects and 8 early onset periodontitis terminal dentition (EOP-TD) subjects were entered into the study. Our purpose was to measure an extended battery of cytokines in the gingival crevicular fluid (GCF) and in lipopolysaccharide (LPS)-stimulated monocytic culture supernatants as well as gingival mononuclear cell messenger RNA (mRNA) transcripts determined from biopsy samples. Within the GCF there were 3 tiers (levels) of mediators based upon approximate 10-fold differences in concentration. The highest tier included prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) and interleukin-2 (IL-2), the intermediate tier included tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN-gamma) and at the lowest concentration level were interleukin-4 (IL-4) and interleukin-6 (IL-6). Thus, the GCF analysis clearly indicated that in both AP-TD and EOP-TD groups the monocytic, i.e. IL-1 beta and PGE2 and Th1, i.e. IL-2 and IFN-gamma, inflammatory mediator levels quantitatively dominated over the Th2 mediators, i.e. IL-4 and IL-6. LPS-stimulated monocytic release of IL-1 beta, PGE2 and TNF alpha was significantly elevated in both AP-TD and EOP-TD groups compared to those of a control group of 21 subjects with moderate to advanced adult periodontitis. The cytokine mRNA expression of isolated gingival mononuclear cells showed that in both the AP-TD and the EOP-TD groups Th1 and Th2 cytokines were expressed, with low levels of IL-4 and IL-12. In conclusion, our data suggest that this cross-sectional TD periodontitis model may reflect progressive periodontal disease associated with tooth loss. Furthermore, although Th1 cytokine levels in the GCF dominate over the Th2 response, monocytic activation provides the main source of proinflammatory mediators. In addition, LPS-stimulated peripheral blood monocytes demonstrate an upregulated inflammatory mediator secretion in the terminal dentition.
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PMID:Inflammatory mediators of the terminal dentition in adult and early onset periodontitis. 968 17

Human beta-defensin-1 (hBD-1) is a member of the family of small cationic antimicrobial peptides that have been identified in several mucosal epithelia. Because human gingival epithelium is a site that is constantly challenged by oral microorganisms, we examined the expression of hBD-1 in human gingival epithelial and fibroblast cell cultures and tissue samples. Cell cultures were challenged with cell wall extracts of Porphyromonas gingivalis or Fusobacterium nucleatum, Escherichia coli lipopolysaccharide, tumor necrosis factor alpha, or phorbol myristate acetate. hBD-1 mRNA was detected in unstimulated and stimulated cultures by reverse transcription (RT)-PCR using several primer sets specific for hBD-1. Gingival epithelial cells, but not gingival fibroblasts, expressed a product of the predicted size for hBD-1 mRNA. The sequence of the PCR product was identical to that of hBD-1. hBD-1 mRNA expression was not significantly modulated by any of the stimulants tested. Human gingival tissues from noninflamed and inflamed sites were also analyzed by RT-PCR. hBD-1 mRNA was expressed in all tissue samples. The relative expression of hBD-1 mRNA was similar in noninflamed and inflamed tissues obtained from each of four patients undergoing treatment for periodontitis. However, the relative expression of hBD-1 mRNA varied in gingival biopsies obtained from 15 different normal individuals, and the relative hBD-1 expression was unrelated to interleukin-8 expression. Our findings show the constitutive expression of hBD-1 mRNA in cultured epithelial cells and gingival tissues but not gingival fibroblasts. These findings suggest that expression of hBD-1 may play a role as part of the innate host defenses in maintaining normal gingival health.
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PMID:Expression of the peptide antibiotic human beta-defensin 1 in cultured gingival epithelial cells and gingival tissue. 971 71

Actinobacillus actinomycetemcomitans(Aa), elaborating a multiplicity of virulence factor and tissue-damaging products, is considered an etiological agent in periodontal disease. Serotype b is the most frequently isolated serotype in localized juvenile periodontitis patients, suggesting a particularly high periodontopathic potential for serotype b strains. Interleukin-6(IL-6) plays an important role in the mediation of inflammatory and immune responses as well as in the osteoclastic bone resorption. However, there is little information regarding the effect of the different serotypes of Aa on IL-6 production by human gingival fibroblasts (HGF). Therefore, the purpose of this study was to compare the ability of the three serotypes (a, b, and c) of Aa sonicates to induce the production of IL-6 by HGF. In fibroblast cultures, confluent monolayers of HGF were incubated with sonic extracts of Aa-511 (serotype a), Aa-Y4 (serotype b), and Aa-652 (serotype c) at various concentrations for 48 h at 37 degrees C in 5% CO2 and air. At the end of the culture period, supernatants were collected and analysed for IL-6 content by using EIA and bioassay. In order to compare the effects of non-lipopolysaccharide (LPS) activation of Aa sonicates on IL-6 production by HGF, we added polymyxin B in cultures with Aa sonicates to bind LPS. The results were summarized as follows. (1) All three serotypes of Aa sonicates had similar dose-dependent stimulant effects on IL-6 production by HGF, and the biological activities of IL-6 correlated with their immunoreactivities. (2) The maximum releases of IL-6 by HGF were achieved at concentrations of 10 to 100 micrograms protein/mL of Aa sonicates, and the ability of Aa-Y4 to induce the release of IL-6 was higher than that of Aa-511 and Aa-652 at these concentrations. (3) Polymyxin B (50 micrograms/mL) effectively decreased the amounts of IL-6 produced by stimulation of the HGF with 10 micrograms protein/mL of Aa sonicates. However, the polymyxin B-treated Aa-Y4 sonicate showed a higher ability to induce the release of IL-6 than the other two strains. These results indicate that Aa-Y4 (serotype b) has a higher potency to induce HGF secretion of IL-6; thus contributing to a comparatively stronger efficacy to the destruction of periodontal tissue in periodontitis.
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PMID:[Interleukin-6 production by human gingival fibroblasts following stimulation with Actinobacillus actinomycetemcomitans]. 971 39

Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used to reduce the inflammation and pain in patients suffering from arthritis. There is a possible use for these drugs in the treatment of inflammation associated with periodontitis. However, the propensity of NSAIDs to cause serious side effects, including gastrointestinal bleeding, has reduced their usefulness. The local application of NSAIDs can avoid these side effects by delivering low doses of drug directly to the affected site. Three NSAIDs (indomethacin, tolmetin and mefenamic acid) were incorporated into polymethylmethacrylate bone cement (PM MA) strips in a range of concentrations and their cytotoxicity, pattern of drug release and ability to suppress elevated levels of prostaglandin E2 (PGE2) in cultured human periodontal ligament fibroblasts (HPLF) assessed. The strips released between 10 and 30% of the total incorporated drug over 7 days, with the highest levels released by strips containing 20% w/w of drug. Strips containing 20% indomethacin and mefenamic acid released in excess of toxic levels in the first 24 h. Strips containing 20, 10 and 5% w/w NSAID significantly (P < 0.05) reduced the level of PGE2 expression by E. coli lipopolysaccharide (LPS) challenged cells, with only the 20% mefenamic acid strip performing significantly better than the other drugs. We conclude that local delivery of NSAIDs using PMMA as a sustained release vehicle is a possible additional tool in the treatment of periodontitis.
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PMID:Assessment of acrylic bone cement as a local delivery vehicle for the application of non-steroidal anti-inflammatory drugs. 972 Aug 93

Severe periodontal disease often coexists with severe diabetes mellitus. Diabetes is a risk factor for severe periodontal disease. A model is presented whereby severe periodontal disease increases the severity of diabetes mellitus and complicates metabolic control. We propose that an infection-mediated upregulation cycle of cytokine synthesis and secretion by chronic stimulus from lipopolysaccharide (LPS) and products of periodontopathic organisms may amplify the magnitude of the advanced glycation end product (AGE)-mediated cytokine response operative in diabetes mellitus. In this model, the combination of these 2 pathways, infection and AGE-mediated cytokine upregulation, helps explain the increase in tissue destruction seen in diabetic periodontitis, and how periodontal infection may complicate the severity of diabetes and the degree of metabolic control, resulting in a 2-way relationship between diabetes mellitus and periodontal disease/infection. This proposed dual pathway of tissue destruction suggests that control of chronic periodontal infection is essential for achieving long-term control of diabetes mellitus. Evidence is presented to support the hypothesis that elimination of periodontal infection by using systemic antibiotics improves metabolic control of diabetes, defined by reduction in glycated hemoglobin or reduction in insulin requirements.
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PMID:Periodontal disease and diabetes mellitus: a two-way relationship. 972 90


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