Search

Aims/introduction: To explore the relationships between periodontitis and microvascular complications as well as glycemic control in type 2 diabetes patients., Materials and Methods: This multicenter, hospital-based, cross-sectional study included 620 patients with type 2 diabetes. We compared the prevalence and severity of periodontitis between patients with ≥1 microvascular complication and those without microvascular complications. We also compared the prevalence and severity of periodontitis among patients with different degrees of glycemic control., Results: After adjusting for confounding factors, multiple logistic regression analysis showed that the severity of periodontitis was significantly associated with the number of microvascular complications (odds ratio 1.3, 95% confidence interval 1.1-1.6), glycated hemoglobin ≥8.0% (64 mmol/mol; odds ratio 1.6; 95% confidence interval 1.1-2.3), and older age (≥50 years; odds ratio 1.7; 95% confidence interval 1.1-2.6). However, the prevalence of periodontitis was not significantly associated with the number of microvascular complications, but was associated with male sex, high glycated hemoglobin (≥8.0% [64 mmol/mol]), older age (≥40 years), longer duration of diabetes (≥15 years) and fewer teeth (≤25). Furthermore, propensity score matching for age, sex, diabetes duration and glycated hemoglobin showed that the incidence of severe periodontitis was significantly higher among patients with microvascular complications than among those without microvascular complications (P < 0.05)., Conclusions: The number of microvascular complications is a risk factor for more severe periodontitis in patients with type 2 diabetes, whereas poor glycemic control is a risk factor for increased prevalence and severity of periodontitis., (© 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Periodontal disease is a less common but important cause of septic pulmonary embolism (SPE). However, the pathogens causing periodontal disease-associated SPE (PD-SPE) have been poorly understood. Actinomyces species are resident microbiota in the oral cavity. Here we report a case of PD-SPE caused by Actinomyces species, which was identified by anaerobic culture of bronchoalveolar lavage fluid (BAL)., Case Presentation: A 64-year-old Asian man, complicated with severe chronic periodontitis, was admitted with chest pain and fever. Chest CT revealed multiple bilateral pulmonary nodules located subpleurally. We diagnosed the case as SPE associated with periodontitis. Although blood cultures were negative for the usual 5-day incubation, anaerobic culture of the BAL fluid sample yielded Actinomyces species. Antibacterial therapy alone did not ameliorate the symptoms; however, additional dental treatment, including tooth extraction, promptly did. The patient was discharged 23 days after admission. The 3-month follow-up revealed no recurrence of the symptoms and complete resolution of the lung lesions., Conclusion: This case demonstrated that Actinomyces species can cause PD-SPE. Additionally, clinicians should consider performing appropriate anaerobic culture of BAL fluid to identify the pathogen of SPE, and to ordering dental treatment, if necessary, in addition to antibiotics for the initial management of PD-SPE.

Background: It was reported that patients with systemic lupus erythematosus (SLE) exhibited increased levels of anticardiolipin (anti-CL) antibodies, a class of antiphospholipid antibodies associated with thrombosis. β2-glycoprotein I (β2GPI) has been considered as the actual target antigen for anti-CL antibodies. This study investigates the association of periodontal infection with anti-CL antibodies in patients with SLE., Methods: Fifty-three SLE female patients and 56 healthy female volunteers were recruited in this case-control study. All participants received periodontal examinations. The presence of Porphyromonas gingivalis and Treponema denticola in saliva and plaque samples was detected by polymerase chain reaction. Levels of serum anti-CL and anti-β2GPI antibodies were examined using enzyme-linked immunosorbent assay., Results: Patients with SLE exhibited more periodontal attachment loss and increased titers of serum anti-CL and anti-β2GPI antibodies compared with healthy controls. Patients with active SLE who harbored P. gingivalis or P. gingivalis together with T. denticola intraorally exhibited significantly higher anti-CL and anti-β2GPI antibodies than those without these bacteria. Anti-CL and anti-β2GPI antibody levels correlated positively with clinical attachment level. Furthermore, increased anti-β2GPI antibody levels were significantly associated with C-reactive protein and erythrocyte sedimentation rate., Conclusions: Elevated anti-CL and anti-β2GPI antibody levels were associated with periodontopathic bacteria and periodontal breakdown in patients with SLE. Periodontitis might be a modifiable risk factor for SLE.

Periodontitis is a multifactorial disease in which bacterial, lifestyle, and genetic factors are involved. Although previous genetic association studies identified several susceptibility genes for periodontitis in European populations, there is little information for Asian populations. Here, we conducted a genome-wide association study and a replication study consisting of 2,760 Japanese periodontitis patients and 15,158 Japanese controls. Although single-nucleotide polymorphisms that surpassed a stringent genome-wide significance threshold (P < 5 × 10(-8)) were not identified, we found 2 suggestive loci for periodontitis: KCNQ5 on chromosome 6q13 (rs9446777, P = 4.83 × 10(-6), odds ratio = 0.82) and GPR141-NME8 at chromosome 7p14.1 (rs2392510, P = 4.17 × 10(-6), odds ratio = 0.87). A stratified analysis indicated that the GPR141-NME8 locus had a strong genetic effect on the susceptibility to generalized periodontitis in Japanese individuals with a history of smoking. In conclusion, this study identified 2 suggestive loci for periodontitis in a Japanese population. This study should contribute to a further understanding of genetic factors for enhanced susceptibility to periodontitis., (© International & American Associations for Dental Research 2015.)

Purpose: Periodontal disease is considered to be a risk factor for threatened preterm labor (TPL) and preterm birth (PB), but pathogenic mechanisms have not yet been elucidated. We hypothesized that infection with periodontopathic bacteria may enhance thrombosis through molecular mimicry with TLRVYK peptides on beta-2 glycoprotein I, a target molecule in anti-phospholipid syndrome. This study aimed to examine the effects of periodontitis on TPL and PB., Methods: Ninety-five pregnant women (47 TPL and 48 healthy subjects) participated. Periodontal clinical parameters and periodontopathic bacteria were examined. Molecular mimicry between TLRVYK peptides and homologous peptides on the periodontopathic bacteria was examined by enzyme-linked immunosorbent assay (ELISA) using rabbit polyclonal antibodies specific for the respective peptides (SIRVYK on Aggregatibacter actinomycetemcomitans, TLRIYT on Porphyromonus gingivalis, and TLALYK on Treponema denticola). Serum high-sensitivity C-reactive protein, anti-TLRVYK and anti-SIRVYK IgG antibodies were measured using ELISA., Results: Among the rabbit antibodies specific for the bacterial homologous peptides, only anti-SIRVYK IgG antibody reacted with TLRVYK peptides. Multivariable analysis showed that anti-SIRVYK IgG antibody was significantly associated with diagnosis of TPL. Of 95 births, 14 (14.7 %) delivered preterm. The preterm birth rate was higher in the anti-SIRVYK IgG antibody >median group than in the ≤median group. Of the 47 TPL subjects 13 had PB, and ordinal logistic regression analysis revealed that past smoking, presence of P. gingivalis and anti-SIRVYK IgG antibody were significantly correlated with PB., Conclusions: Infection with P. gingivalis and the antibody response to SIRVYK might be associated with TPL and PB.

Wingless proteins, termed Wnt, are involved in embryonic development, blood cell differentiation, and tumorigenesis. In mammalian hematopoiesis, Wnt signaling is essential for stem-cell homeostasis and lymphocyte differentiation. Recent studies have suggested that these molecules are associated with cardiovascular diseases, rheumatoid arthritis, and osteoarthritis. Furthermore, Wnt5a signaling is essential for the general inflammatory response of human macrophages. Periodontitis is a chronic inflammatory disease caused by gram-negative periodontopathic bacteria and the resultant host immune response. Periodontitis is characterized by loss of tooth-supporting structures and alveolar bone resorption. There have been no previous reports on Wnt5a expression in periodontitis tissue, and only few study reported the molecular mechanisms of Wnt5a expression in LPS-stimulated monocytic cells. Using RT-PCR, we demonstrated that Wnt5a mRNA expression was up-regulated in chronic periodontitis tissue as compared to healthy control tissue. P. gingivalis LPS induced Wnt5a mRNA in the human monocytic cell line THP-1 with a peak at 4 hrs after stimulation. P. gingivalis LPS induced higher up-regulation of Wnt5a mRNA than E. coli LPS. The LPS receptors TLR2 and TLR4 were equally expressed on the surface of THP-1 cells. P. gingivalis LPS induced IκBα degradation and was able to increase the NF-κB binding activity to DNA. P. gingivalis LPS-induced Wnt5a expression was inhibited by NF-κB inhibitors, suggesting NF-κB involvement. Furthermore, IFN-γ synergistically enhanced the P. gingivalis LPS-induced production of Wnt5a. Pharmacological investigation and siRNA experiments showed that STAT1 was important for P. gingivalis LPS-induced Wnt5a expression. These results suggest that the modulation of Wnt5a expression by P. gingivalis may play an important role in the periodontal inflammatory process and serve a target for the development of new therapies.

Periodontitis is regarded to have a close relationship to diabetes mellitus. In Japan, some cohort studies have indicated that there is a significant positive association of obesity plus metabolic syndrome with periodontal diseases. As such, an increasing number of studies suggest a relationship between periodontitis and diabetes, most of which are epidemiologic association. In this review, we have summarized the possible evidence of a relationship between periodontitis and diabetes. To date, little evidence has been reported to indicate that diabetes and/or glucose intolerance has in fact had a significant cause-effect relationship with periodontal disease. In this regard, it is important to directly uncover the relation, i.e., to prove the effect of therapeutic approaches to periodontitis upon mitigation of glycemic control in diabetic patients, which would be a direct evidence of its causal nature. Therefore a study should be undertaken to this effect.

Aim: Anti-cardiolipin (CL) antibodies can be induced in Buerger disease (BD), an inflammatory occlusive disorder affecting peripheral blood vessels, in response to bacteria bearing homology to the TLRVYK peptide of a phospholipid-binding plasma protein beta-2-glycoprotein I. TLRVYK homologies are present in Porphyromonas gingivalis (TLRIYT) and Treponema denticola (TLALYK). This study investigated the association between periodontal infection and anti-CL antibodies in BD patients., Material and Methods: Periodontal conditions were examined in 19 BD patients and 25 systemically healthy control subjects. All subjects were heavy smokers. Serum anti-CL, anti-TLRVYK, anti-TLRIYT, and anti-TLALYK antibodies were assessed using the enzyme-linked immunosorbent assay., Results: BD patients had a significantly higher prevalence of periodontitis, more severe periodontal destruction and increased titres of serum anti-CL, anti-TLRVYK, anti-TLRIYT, and anti-TLALYK antibodies compared with healthy subjects. The levels of anti-CL antibodies positively correlated with those of the three anti-peptide antibodies. Anti-CL antibody titres were significantly associated with the percentage of sites with clinical attachment level >or=4 mm in BD patients., Conclusion: Elevated anti-CL antibody levels were associated with periodontal destruction in BD patients. Periodontopathic bacteria may serve as exogenous antigens that stimulate the anti-CL antibody production through molecular mimicry between the bacterial peptides and a host plasma protein.

Objectives: The aim of this case control study was to evaluate whether periodontitis was associated with peripheral arterial disease (PAD)., Subjects and Methods: Twenty-five patients diagnosed with aorto-iliac and/or femoro-popliteal occlusive disease and thirty-two generally healthy control subjects were enrolled in this study. Polymerase chain reaction (PCR) was used to identify Porphyromonas gingivalis, Treponema denticola, Actinobacillus actinomycetemcomitans, Prevotella intermedia, Cytomegalovirus (CMV), Chlamydia pneumoniae, and Helicobacter pylori in tissue specimens taken from the anastomotic site of distal bypasses. Periodontal status was evaluated; serum IgG titres against the four listed bacteria were measured., Results: Periodontopathic bacteria were detected in 13/25 (52%) atherosclerotic specimens. CMV or C. pneumoniae was detected in 1/25 (4%) specimens; H. pylori was not detected from any of these specimens. Fontaine grade III or IV patients showed higher detection frequency of P. gingivalis than Fontaine grade II patients (57.1% vs 22.2%, P=0.09). After adjusting for age, gender, diabetes and smoking, periodontitis increased 5-fold the risk of having PAD (OR 5.45). There were preliminary indications that periodontitis was associated with increased serum IL-6 and TNF-alpha concentrations., Conclusions: This study suggests that periodontitis may be associated with an increased risk of PAD. This association could result from the increased concentration of serum inflammatory cytokines in those with periodontitis.

Aggressive periodontitis (AgP), a severe and early onset type of periodontitis, is thought to be subject to significant genetic background effects. Formyl peptide receptor 1 (FPR1) is a gene strongly implicated in AgP. To determine whether variations in this gene are associated with AgP, we performed an association study with 49 AgP patients and 373 controls using 30 variations identified by sequencing the 21.1-kb gene region. Five polymorphisms (-12915C>T, -10056T>C, -8430A>G, 301G>C, and 546C>A) showed significant association with AgP. Polymorphonuclear neutrophils from subjects carrying the -12915T allele expressed significantly lower levels of FPR1 transcripts than those homozygous for the -12915C allele. Furthermore, the -12915T allele decreased activity of transcriptional regulation in a luciferase assay. Haplotype association analysis with three SNPs (-12915C>T, 301G>C, and 546C>A) revealed that one haplotype (-12915T-301G-546C) was significantly represented in AgP patients (p=0.000020). Thus, altered FPR1 function might confer increased risk to AgP.

Recent epidemiological studies suggest that periodontitis is an important risk factor for coronary heart disease (CHD). The aim of this study was to evaluate the association between periodontitis and CHD, particularly acute coronary syndrome (ACS), focusing on microbiological and immunological features. Twenty-eight CHD patients, 15 with ACS and 13 with chronic CHD, were included in this study. Coronary angiography, periodontal examination, and dental radiography were performed in all patients. Subgingival plaque, saliva, and blood samples were analyzed for the periodontopathogens Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, and Prevotella intermedia using polymerase chain reaction. Specific serum antibody titers to the 5 periodontal pathogens were determined by enzyme-linked immunosorbent assay. It was found that 33% of the ACS patients (5/15) harbored A. actinomycetemcomitans in oral samples, whereas no A. actinomycetemcomitans (0/13) was found in the chronic CHD patients (P < 0.05). Furthermore, ACS patients showed significantly higher serum IgG titers to A. actinomycetemcomitans (P < 0.05) compared with chronic CHD. More tooth loss and alveolar bone loss were noted in ACS patients than in chronic CHD patients, although the differences were not statistically significant. Periodontal pathogens, particularly A. actinomycetemcomitans, may play a role in the development of ACS.

Periodontitis is an inflammatory bone disease caused by Gram-negative anaerobic bacteria. Osteoclast differentiation is regulated by the balance between receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG). The purpose of this study was to examine the mechanism of OPG production in human gingival fibroblasts (HGF) stimulated by lipopolysaccharide (LPS) from periodontopathic bacteria. The expressions of Toll-like receptor 2 (TLR-2) and TLR-4 in HGF were examined using flow-cytometry. HGF were stimulated with whole cell extracts or LPS from Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis with or without polymyxin B, a LPS inhibitor. In addition, HGF were stimulated with LPS, prostaglandin E(2) (PGE(2)), various agonists of PGE receptors (EP1, EP2, EP3 and EP4 agonists) with or without indomethacin (IND), a prostaglandin synthesis inhibitor. OPG and PGE(2) production was measured using an enzyme-linked immunosorbent assay (ELISA). HGF expressed both TLR-2 and TLR-4. Both A. actinomycetemcomitans and P. gingivalis LPS augmented OPG expression in HGF. Whole cell extracts from A. actinomycetemcomitans and P. gingivalis augmented OPG production by HGF; the augmentation was suppressed by polymyxin B. IND suppressed OPG production in LPS-stimulated HGF. PGE(2) stimulated HGF to produce OPG. EP1 and EP2 agonists, but not EP3 and EP4 agonists, increased OPG production by HGF. These results suggest that LPS-induced OPG production by HGF is regulated via EP1 and/or EP2 receptors by endogenously generated PGE(2).

Background/aims: The immunoglobulin G (IgG) antibody response is considered to be protective and beneficial for the control of periodontal lesions. This study analysed IgG subclass antibody levels of Porphyromonas gingivalis in patients with both aggressive periodontitis (AgP) and chronic periodontitis (CP)., Methods: Subgingival plaque and peripheral blood samples were collected from patients with localized AgP (n = 13), generalized AgP (n = 28) and generalized CP (n = 27) and from 14 periodontally healthy controls. P. gingivalis was identified in subgingival pockets using a polymerase chain reaction. Simultaneously, serum IgG subclass antibody against P. gingivalis whole cells/P. gingivalis fimbriae were measured using enzyme-linked immunosorbent assay., Results: P. gingivalis was frequently detected in periodontitis patients. Anti-P. gingivalis whole cell IgG1 was elevated in all P. gingivalis-positive patients in the three periodontitis groups. Although increased anti-P. gingivalis IgG1 was also observed in the bacterium-positive healthy controls, the level was lower than that found in the three periodontitis groups. Levels of IgG1, IgG2, IgG3 and IgG4 to P. gingivalis did not differ among bacterium-positive patients in the three periodontitis groups; a significant increase of IgG2 level was not observed in localized AgP. Anti-fimbriae IgG subclass levels of IgG1, IgG2 and IgG4 did not differ among bacterium-positive subjects in all groups, while the anti-fimbriae IgG3 level in generalized CP was significantly higher than that in localized and generalized AgP., Conclusions: P. gingivalis infection elicited an IgG subclass antibody response in both periodontitis patients and healthy subjects, while higher anti-P. gingivalis IgG1 levels were found in the three periodontitis groups compared with the healthy control group.

Background: The aim of this randomized controlled clinical trial was to determine the effects of single-visit full-mouth ultrasonic debridement versus quadrant-wise therapy., Material and Methods: Thirty-six subjects with chronic periodontitis, were randomly allocated to three groups--quadrant-wise ultrasonic debridement, single-visit full-mouth ultrasonic debridement with povidone iodine and single-visit full-mouth ultrasonic debridement with water. Whole-mouth plaque, bleeding on probing (BOP), pocket depth and attachment level were recorded before treatment and 1, 3 and 6 months post-treatment. Plaque and saliva samples were collected for microbiological analysis., Results: After treatment, all groups showed significant improvement in clinical parameters. Full-mouth treatments resulted in similar improvements in full-mouth mean plaque percentage, probing pocket depth and probing attachment level as conventional therapy. When data were analysed based on pocket depth and tooth type, there was no difference between groups in probing depth reduction or attachment gains. The full-mouth groups demonstrated greater reduction in BOP% and number of pockets > or =5 mm and the total treatment time was significantly shorter. The detection frequencies of periodontal pathogens in plaque and saliva showed slight changes with no difference between groups., Conclusion: Single-visit full-mouth mechanical debridement may have limited additional benefits over quadrant-wise therapy in the treatment of periodontitis, but can be completed in a shorter time.

Aim: The purpose of this study was to characterize serum antibody responses to different serotypes of Actinobacillus actinomycetemcomitans strains in various forms of periodontitis and to determine whether any specific type of A. actinomycetemcomitans was associated with any specific form of periodontitis in a Japanese population., Methods: Sonicated whole cell and autoclaved serotype antigens of A. actinomycetemcomitans were used. Serum IgG titer and avidity to A. actinomycetemcomitans were measured by enzyme-linked immunoabsorbant assay (ELISA) and ammonium thiocyanate-dissociation ELISA, respectively, in 46 aggressive periodontitis patients (8 localized, 38 generalized), 28 chronic periodontitis patients, and 18 periodontally healthy subjects. The presence of A. actinomycetemcomitans in plaque and saliva samples was determined using polymerase chain reaction., Results: Generalized aggressive and chronic periodontitis patients exhibited significantly higher IgG titers than healthy subjects to both sonicated and autoclaved antigens of serotype c strains, while IgG titer to serotype b (Y4) was significantly higher in localized aggressive periodontitis patients compared to healthy subjects. No A. actinomycetemcomitans was detected in localized aggressive periodontitis patients. A. actinomycetemcomitans-positive patients exhibited significantly higher IgG titer and avidity to serotype c than A. actinomycetemcomitans-negative patients. In A. actinomycetemcomitans-positive patients, a significantly positive correlation was observed between antibody titer and avidity to serotype c. A. actinomycetemcomitans-positive patients with generalized aggressive periodontitis showed lower IgG avidities to serotype c than those with chronic periodontitis, though no statistically significant difference was found., Conclusion: A. actinomycetemcomitans serotype c may play a significant role in chronic and generalized aggressive periodontitis, while A. actinomycetemcomitans serotype b may be associated with localized aggressive periodontitis in a Japanese population.

Background and Objective: Peripheral blood monocytes are a heterogeneous population, with phenotypes that change on activation or differentiation. Most of the monocytes express lipopolysaccharide (LPS) receptor, CD14 intensely, and do not express Fc gamma receptor III, CD16 (CD14++CD16- monocytes). But monocytes expressing CD16 with reduced CD14 (CD14+CD16+ monocytes) increase in inflammatory diseases as well as sepsis and bacteremia in hemodialysis patients. CD45RA is expressed on activated monocytes, and is regarded as an activation marker of peripheral blood monocytes. The purpose of this study was to determine the phenotypic and functional alteration of monocytes in periodontitis patients., Methods: Peripheral blood was collected from 33 aggressive periodontitis patients (22 females, 11 males), 55 chronic periodontitis patients (35 females, 20 males) and 30 healthy subjects (16 females, 14 males), and the expression of CD14, CD16 and CD45RA on monocytes was determined using flow cytometry. The production of interleukin-6 (IL-6) by CD16+ and CD16- monocytes stimulated with LPS from Escherichia coli and Actinobacillus actinomycetemcomitans was also examined using flow cytometry., Results: The percentage of CD14+CD16+ monocytes was significantly increased in chronic periodontitis patients. Percentage of monocytes expressing CD45RA was significantly increased in aggressive periodontitis patients compared to healthy subjects. CD16+ and CD16- monocytes produced IL-6 in response to LPS from E. coli and A. actinomycetemcomitans, and the percentage of IL-6 producing cells was higher in CD16+ monocytes than CD16- monocytes, suggesting that CD14+CD16+ monocytes represent a hyper-reactive phenotype., Conclusions: The present study demonstrated that CD14+CD16+ monocytes and CD45RA+ monocytes were increased in chronic and aggressive periodontitis, respectively. These findings suggest that alteration of monocytes in periodontitis patients could be evaluated by monitoring the surface expression of CD14, CD16 and CD45RA on monocytes.

Periodontitis is an inflammatory bone disease caused by Gram-negative anaerobic bacteria, but the precise mechanism of bone destruction remains unknown. Activated T lymphocytes secrete receptor activator of NF-kappaB ligand (RANKL) and support the differentiation of monocytes into mature osteoclasts. The purpose of this study was to examine the expression of RANKL and its inhibitor, osteoprotegerin (OPG), in inflamed gingival tissue and to clarify the role of human gingival fibroblasts (HGFs) in osteoclastogenesis regulated by RANKL. HGFs and gingival mononuclear cells (GMCs) were obtained from chronic periodontitis patients during routine periodontal surgery. Expression of OPG and RANKL mRNA in gingival tissue and HGFs was examined with RT-PCR. OPG production was measured using ELISA. Expression of RANKL, CD4, CD8 and CD69 on GMCs was determined by flow-cytometry using RANK-Fc fusion protein and the respective monoclonal antibodies. Osteoclastogenesis by RANKL was assayed by counting the number of tartarate-resistant acid phosphatase (TRAP)-positive cells after culturing human peripheral blood monocytes with recombinant human RANKL and macrophage-colony stimulating factor (M-CSF) for 10 days. OPG and RANKL mRNA were expressed in 80% (16/20) and 25% (5/20) of periodontitis lesions, respectively. OPG, but not RANKL, mRNA was expressed within HGFs. OPG mRNA expression and production by HGFs was augmented by LPS stimulation. All GMC samples expressed CD69, and two of five GMC samples expressed RANKL. The culture supernatant of LPS-stimulated gingival fibroblasts significantly reduced the number of TRAP positive cells generated by culturing monocytes with RANKL and M-CSF. The present study suggests that LPS-stimulated HGFs inhibit monocyte differentiation into osteoclasts through the production of OPG.

T cells and their cytokines are well known for their important role in the pathogenesis of periodontitis. To date, the role of antigen presenting cells (APCs), which are known to be critical in the regulation of T cell response, has been poorly investigated in periodontitis. In this study, we analyzed the expression of co-stimulatory molecules (CD80 and CD86) and CD83, which is a marker of mature dendritic cells, on gingival cells that were isolated from severe periodontitis tissues, with the use of flow cytometry. Significant upregulation of CD86 and CD83 expression was detected in periodontitis lesions, and most of this occurred on B cells. In vitro peripheral blood mononuclear cell cultures showed that stimulation with different periodontopathic bacteria, that included Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia, and Actinomyces viscosus, upregulated both CD86 and CD83 expression on B cells. Therefore, the presence of plaque bacteria may be responsible for the enhanced expression seen in vivo on gingival B cells. APC function by bacterial-activated B cells was further investigated using allogeneic mixed leukocyte reactions. After 24 h culture with either A. actinomycetemcomitans or P. gingivalis, these activated B cells performed as potent APCs in mixed leukocyte reactions, and they stimulated T cells to produce high levels of gamma interferon and minimal interleukin-5. In conclusion, periodontopathic bacterial-induced B cell activation with upregulation of CD86 and CD83 may be associated with enhanced APC function. The results of this study suggest, therefore, that infiltrated gingival B cells have a possible role as APCs in the regulation and maintenance of local T cell response in periodontitis.

Polarization of type 1 (Th1) or type 2 (Th2) immune responses determines the prognosis of many infectious diseases. Interferon gamma (IFN-gamma) and IL-4 are key cytokines for the development of type 1 and type 2 immune responses, respectively. The aim of this study was to examine individual diversities in the polarization of type 1 and type 2 responses against periodontopathic bacteria. Peripheral blood mononuclear cells (PBMCs) from adult periodontitis (AP) patients and healthy (H) subjects were stimulated with Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Bacteroides forsythus with or without polymyxin-B, CTLA-4 Ig and anti-IL-12 antibody. IFN-gamma, IL-4 and IL-12 in the culture supernatant were measured. IFN-gamma and IL-4 producing cells were also examined using a multiparameter flow cytometric assay. Bone resorption rate in AP patients was calculated using Schei's method, and the probing pocket depth was also measured. PBMCs from AP patients and H subjects produced IFN-gamma and IL-12, whereas the production of IL-4 was rarely observed. Among the bacteria tested, A. actinomycetemcomitans was the most potent inducer of IFN-gamma and IL-12, and the reaction was inhibited by polymyxin-B. IFN-gamma was found to be produced by T cells in the PBMCs, and the production was significantly reduced by CTLA-4 Ig and anti-IL-12 neutralizing antibody. The amount of IFN-gamma produced by the PBMCs of AP patients and H subjects varied among individuals, and was significantly correlated with the amount of IL-12 produced in a particular individual. The production of IFN-gamma was not related with periodontal condition which was evaluated using bone resorption and pocket depth. These results suggest that polarization of type 1 response against periodontopathic bacteria is dependent on the production of IL-12 by monocytes, and that IL-12 stimulates IFN-gamma production. However, individual diversities of IFN-gamma production might not be directly related to the severity of periodontitis.

The peripheral blood T-cell phenotype of patients with rapidly progressive periodontitis (RPP) was determined in order to investigate whether there were T-cell imbalances or not. Twenty patients aged 21-39 yr were selected for this study. Bone resorption and probing pocket depth were measured. All the patients had 10 or more teeth showing bone loss of 50% or more. As controls, 12 periodontally healthy, age-matched individuals were selected. Blood samples were obtained by venipuncture, and lymphocytes were isolated. Two-colour flow cytometric analysis was done with monoclonal antibodies against human CD4, CD8, and CD45RA antigens. The RPP patients were found to have significantly lower percentage of CD8+ T cells (Mann-Whitney's U-test, p < 0.01) and an increased CD4/CD8 ratio (Mann-Whitney's U-test, p < 0.01) compared with healthy individuals. On the other hand, there were no significant differences in the percentages of CD4+ T cells and CD4+ CD45RA+ T cells between RPP patients and healthy individuals. No correlations between the clinical findings and T-cell subsets were found. These findings suggest that imbalances of peripheral blood T lymphocytes, especially a tendency to decreased CD8 + T cells, exist in RPP patients, and that cellular immune responses mediated by CD8 + T cells may play a part in the pathogenesis of RPP.

Chronic periodontitis is a silent infectious disease prevalent worldwide and affects lifestyle-related diseases. Therefore, efficient screening of patients is essential for general health. This study was performed to evaluate prospectively the diagnostic utility of a blood IgG antibody titer test against periodontal pathogens. Oral examination was performed, and IgG titers against periodontal pathogens were measured by ELISA in 1,387 individuals. The cut-off value of the IgG titer was determined in receiver operating characteristic curve analysis, and changes in periodontal clinical parameters and IgG titers by periodontal treatment were evaluated. The relationships between IgG titers and severity of periodontitis were analyzed. The best cut-off value of IgG titer against Porphyromonas gingivalis for screening periodontitis was 1.682. Both clinical parameters and IgG titers decreased significantly under periodontal treatment. IgG titers of periodontitis patients were significantly higher than those of healthy controls, especially in those with sites of probing pocket depth over 4 mm. Multiplied cut-off values were useful to select patients with severe periodontitis. A blood IgG antibody titer test for Porphyromonas gingivalis is useful to screen hitherto chronic periodontitis patients (ClinicalTrials.gov number NCT01658475). [ABSTRACT FROM PUBLISHER]

Background: Periodontitis is a chronic inflammatory disease characterized by the enhanced expression of inflammatory mediators leading to alveolar bone resorption. Osteoprotegerin (OPG) plays a suppressive role in cytokine-induced osteoclastogenesis. In osteoblasts, OPG expression is upregulated by β-catenin but downregulated by the transcription factor activator protein-1 (AP-1; c-fos/ c-jun). The purpose of this study was to examine the roles of β-catenin and AP-1 in interleukin-1α (IL-1α) -induced OPG production in human gingival fibroblasts (hGFs) and periodontal ligament (PDL) cells. Methods: Expression of c-fos and c- jun messenger RNA was measured by reverse transcription-polymerase chain reaction and OPG production was analysed by enzyme-linked immunosorbent assay. The nuclear AP-1 activity was quantified using an AP-1 microplate assay. The effect of the Wnt canonical pathway on OPG production was evaluated using small interfering (si) RNA for β-catenin and the effect of AP-1 on OPG production was evaluated using the AP-1 inhibitor curcumin. Results: Levels of c- fos messenger RNA and nuclear AP-1 activity were higher in PDL cells than in hGFs. When stimulated with IL-1α, PDL cells had significantly higher c- fos expression and lower OPG production compared with hGFs. The siRNA for β-catenin suppressed the IL-1α-induced OPG production in both PDL cells and hGFs, whereas the AP-1 inhibitor curcumin augmented the IL-1α-induced OPG production in PDL cells, but not in hGFs. Conclusion: The present study suggests that β-catenin enhances IL-1α-induced OPG production in both PDL cells and hGFs, whereas AP-1 suppresses IL-1α-induced OPG production in PDL cells. Higher expression of c- fos in PDL cells than in hGFs may implicate a role of PDL cells in alveolar bone resorption in periodontitis. [ABSTRACT FROM AUTHOR]

Introduction: β2-Glycoprotein I (β2GPI) is important in the suppression of coagulation, and antibodies against TLRVYK peptides on the β2GPI molecule are related to thrombosis. According to the Swiss-Prot database, Aggregatibacter actinomycetemcomitans leukotoxin c has sequences (SIRVYK) that are homologous to the TLRVYK peptides. The aim of this study was to investigate the effects of A. actinomycetemcomitans infection on the antibody response against SIRVYK peptides in patients with periodontitis. Methods: Serum immunoglobulin G (IgG) antibody and IgG subclass antibody titers against SIRVYK or TLRVYK peptides were measured by enzyme-linked immunosorbent assay in 46 patients with aggressive periodontitis (eight with localized disease, 38 with generalized disease), 28 patients with chronic periodontitis, and 20 periodontally healthy subjects. The presence of A. actinomycetemcomitans in plaque and saliva samples was determined using polymerase chain reaction. Results: The level of anti-SIRVYK antibodies was significantly higher in patients who were A. actinomycetemcomitans-positive than in A. actinomycetemcomitans-negative patients ( P < 0.05) in the chronic periodontitis group. A similar trend was found in the antibody response to TLRVYK peptide; however, no statistically significant difference was seen between A. actinomycetemcomitans-positive and -negative patients. The A. actinomycetemcomitans-positive patients displayed significantly higher levels of anti-SIRVYK IgG2 and IgG3 antibodies than A. actinomycetemcomitans-negative patients ( P < 0.05 and P < 0.05, respectively). The level of IgG2 was highest among the four IgG subclasses and it predominantly increased in patients who were A. actinomycetemcomitans-positive. Anti-TLRVYK antibody levels were significantly correlated with anti-SIRVYK IgG antibody levels. Conclusion: The results suggest that A. actinomycetemcomitans infection may elicit anti-SIRVYK IgG antibodies and modify the anti-TLRVYK antibody response in patients with periodontitis by molecular mimicry with β2GPI. [ABSTRACT FROM AUTHOR]

Periodontitis, a chronic inflammatory disease, is characterized by increased expression of interleukin (IL)-1 and other inflammatory mediators resulting in extensive osteoclast formation and bone loss. Expression of receptor activator of nuclear factor kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG), by osteoblasts is important to regulate osteoclast differentiation. The aim of the present study was to investigate the regulatory effects of IL-1 on RANKL and OPG production by mesenchymal fibroblasts in periodontal tissue. Human gingival fibroblasts (HGF) and periodontal ligament fibroblasts (PDL) were stimulated with IL-1α with or without protein synthesis inhibitor cycloheximide (CHX), protein kinase A (PKA) inhibitors, protein kinase C (PKC) inhibitors and prostaglandin E2 (PGE2) inhibitor. In some experiments, the cultured cells were directly stimulated with either PKA or PKC activators. In HGF, IL-1α-stimulated OPG mRNA expression was high and could be reduced by CHX. PKA inhibitor completely abrogated IL-1α-induced OPG mRNA expression and OPG production. Endogenous PGE2 further enhanced IL-1α-induced OPG production in HGF. In PDL, RANKL mRNA expression was greatly augmented by IL-1α. IL-1α induced OPG mRNA expression and protein production. PKC inhibitor partially reduced IL-1α-induced OPG production and PKC activator enhanced OPG production in PDL. The IL-1α-stimulated OPG mRNA expression in HGF was greater than PDL. These results provide new evidence for the possible osteoclastogenesis-inhibitory function of HGF through PKA activity pathway. PDL utilized PKC for OPG production. Thus, we emphasize that HGF and PDL have different characteristics of host defence mechanism against inflammatory process. [ABSTRACT FROM AUTHOR]

Wang D, Kawashima Y, Nagasawa T, Takeuchi Y, Kojima T, Umeda M, Oda S, Ishikawa I. Elevated serum IgG titer and avidity toActinobacillus actinomycetemcomitansserotype c in Japanese periodontitis patients.Oral Microbiol Immunol 2005: 20: 172–179© Blackwell Munksgaard, 2005.The purpose of this study was to characterize serum antibody responses to different serotypes ofActinobacillus actinomycetemcomitansstrains in various forms of periodontitis and to determine whether any specific type ofA. actinomycetemcomitanswas associated with any specific form of periodontitis in a Japanese population.Sonicated whole cell and autoclaved serotype antigens ofA. actinomycetemcomitanswere used. Serum IgG titer and avidity toA. actinomycetemcomitanswere measured by enzyme-linked immunoabsorbant assay (ELISA) and ammonium thiocyanate-dissociation ELISA, respectively, in 46 aggressive periodontitis patients (8 localized, 38 generalized), 28 chronic periodontitis patients, and 18 periodontally healthy subjects. The presence ofA. actinomycetemcomitansin plaque and saliva samples was determined using polymerase chain reaction.Generalized aggressive and chronic periodontitis patients exhibited significantly higher IgG titers than healthy subjects to both sonicated and autoclaved antigens of serotype c strains, while IgG titer to serotype b (Y4) was significantly higher in localized aggressive periodontitis patients compared to healthy subjects. NoA. actinomycetemcomitanswas detected in localized aggressive periodontitis patients.A. actinomycetemcomitans-positive patients exhibited significantly higher IgG titer and avidity to serotype c thanA. actinomycetemcomitans-negative patients. InA. actinomycetemcomitans-positive patients, a significantly positive correlation was observed between antibody titer and avidity to serotype c.A. actinomycetemcomitans-positive patients with generalized aggressive periodontitis showed lower IgG avidities to serotype c than those with chronic periodontitis, though no statistically significant difference was found.A. actinomycetemcomitansserotype c may play a significant role in chronic and generalized aggressive periodontitis, whileA. actinomycetemcomitansserotype b may be associated with localized aggressive periodontitis in a Japanese population. [ABSTRACT FROM AUTHOR]