The role of T cells in periodontal disease: homeostasis and autoimmunity.
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Aggregatibacter actinomycetemcomitans↗
Biomedical subjects
Kazuhisa Yamazaki
Publications and source records attributed to Kazuhisa Yamazaki.
Effect of periodontal treatment on the C-reactive protein and proinflammatory cytokine levels in Japanese periodontitis patients.
BACKGROUND: Recent epidemiological studies have shown that individuals with periodontitis have a significantly increased risk of developing coronary heart disease. In addition to conventional risk factors, chronic infection and subsequent production of systemic inflammatory markers may be associated with this increased risk. OBJECTIVES: The aim of the present study was to determine whether the presence of chronic periodontitis and subsequent periodontal treatment could influence the serum levels of C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-alpha (TNF-alpha) in a Japanese population. METHODS: Sera were obtained from 24 patients with moderate to advanced periodontitis at the baseline examination and at reassessment after completion of treatment. As a control, sera were also obtained from 21 subjects without periodontitis. High-sensitivity CRP (hs-CRP) was measured using nephelometry with a latex particle-enhanced immunoassay and interleukin-6 and TNF-alpha were determined by sensitive enzyme-linked immunosorbent assay. RESULTS: The levels of hs-CRP and interleukin-6 in the sera of this Japanese population seemed to be much lower than those reported in other populations. TNF-alpha on the other hand, demonstrated similar levels between this Japanese and other populations. Periodontal status demonstrated a significant improvement in all patients following treatment. There was a trend toward higher hs-CRP levels in patients at baseline compared with control subjects. Hs-CRP level tended to decrease with improvement of the periodontal condition following treatment and approached that of control subjects, although this decline was not statistically significant. interleukin-6 and TNF-alpha levels did not change following periodontal treatment. Furthermore, there was no difference in the serum levels of these inflammatory cytokines between patients either at baseline or at reassessment and control subjects. CONCLUSIONS: In this pilot study, we were unable to show that periodontal disease significantly affects the serum levels of systemic inflammatory markers. However, this does not necessarily mean that periodontitis does not contribute to the total burden of inflammation as there was a tendency for hs-CRP to decrease following successful periodontal treatment. Large-scale studies are clearly needed to determine the impact of periodontal disease on systemic inflammation.
Adult↗
[Periodontitis and tissue regeneration].
Chronic periodontitis is a destructive disease that affects the supporting structures of the teeth including periodontal ligament, cementum, and alveolar bone. If left untreated, patients may lose multiple teeth and extensive prosthetic treatment will be required. In order to re-engineer lost tooth-supporting tissues, various therapeutic modalities have been used clinically. Periodontal regeneration procedures including guided tissue regeneration have achieved substantial effects. However, there are several issues to be solved. They are highly technique-sensitive, applicable to limited cases which are susceptible to treatment, and supposed to have relatively low predictability. Therefore, it is necessary to develop new approaches to improve the predictability and effectiveness of regenerative therapies for periodontal tissues. Recently, the concept of tissue engineering has been introduced to restore lost tissues more effectively where the biological process of healing is mimicked. To achieve this, integration of three key elements is required: progenitor/stem cells, growth factors and the extracellular matrix scaffold. Although it has been shown that implantation of bone marrow-derived mesenchymal stem cells into periodontal osseous defects induced regeneration of cementum, periodontal ligament and alveolar bone in dogs, further extensive preclinical studies are required. On the other hand, application of growth factors, particularly basic fibroblast growth factor in the treatment of human periodontitis, is promising and is now in clinical trial. Furthermore, the rate of release of growth factor from the scaffold also can profoundly affect the results of tissue engineering strategies and the development of new materials is expected. In addition, as tissue regenerative potential is negatively regulated by aging, the effects of aging have to be clarified to gain complete regeneration.
Animals↗
Antigen specificity and T-cell clonality in periodontal disease.
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Animals↗
Association of tumor necrosis factor receptor type 2 +587 gene polymorphism with severe chronic periodontitis.
BACKGROUND: Genetic polymorphisms for cytokines and their receptors have been proposed as potential markers for periodontal disease. Tumor necrosis factor receptor 2 (TNFR2) is one of the cell surface receptors for TNF-alpha. Recent studies have suggested that TNFR2 gene polymorphism is involved in autoimmune and other diseases. OBJECTIVES: The aim of the present study is to evaluate whether TNFR2(+587T/G) gene polymorphism is associated with chronic periodontitis (CP). METHODS: One hundred and ninety-six unrelated subjects (age 40-65 years) with different levels of CP were identified according to established criteria, including measurements of probing pocket depth (PPD), clinical attachment level (CAL), and alveolar bone loss (BL). All subjects were of Japanese descent and non-smokers. Single nucleotide polymorphism at position +587(T/G) in the TNFR2 gene was detected by a polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. RESULTS: The frequency and the positivity of the +587G allele were significantly higher in severe CP patients than in controls (p=0.0097; odds ratio=2.61, p=0.0075; odds ratio=3.06). In addition, mean values of PPD, CAL, and BL were significantly higher in the +587G allele positive than in the negative subjects (p=0.035, 0.022, and 0.018, respectively). CONCLUSIONS: These findings suggest that the TNFR2(+587G) polymorphic allele could be associated with severe CP in Japanese.
Adult↗
Matrix metalloproteinase-1 and -3 gene promoter polymorphisms in Japanese patients with periodontitis.
BACKGROUND/AIMS: Matrix metalloproteinase (MMP)-1 and MMP-3 have important roles in the connective tissue remodelling and destruction processes in periodontitis. MMP-1 1G/2G (-1607) and MMP-3 5A/6A (-1171) polymorphisms have been identified and appear to influence the transcription of the genes. The aim of this study was to investigate whether these gene promoter polymorphisms were associated with the susceptibility to periodontitis. MATERIAL AND METHODS: Genomic DNA was obtained from 37 generalised aggressive, 205 slight-to-severe generalised chronic-periodontitis patients and 142 healthy subjects. All subjects were non-smoking Japanese. We genotyped by using TaqMan PCR assay. The statistics were analysed by chi2-test. RESULTS: We found no significant differences in genotype distributions, allele frequencies, carriage rates and haplotype frequencies in the MMP-1 and the MMP-3 gene promoter polymorphisms among all groups. The distributions of MMP-1 and MMP-3 genotypes in our study were different from those of previously reported in Caucasians or Brazilians, but consistent with previously reported in Japanese. CONCLUSION: Our data did not support the hypothesis that MMP-1 and/or MMP-3 gene promoter polymorphisms influenced the susceptibility to periodontitis in Japanese patients, indicating MMP-1 and MMP-3 expressions were regulated by complex processes such as cytokine network in periodontal disease rather than gene polymorphisms.
Adult↗
Effects of Nd:YAG and CO2 laser treatment and ultrasonic scaling on periodontal pockets of chronic periodontitis patients.
BACKGROUND: The aim of the present study was to compare the effectiveness of Nd:YAG and CO2 laser treatment to that of ultrasonic scaling used as monotherapies by examining clinical parameters, subgingival microflora, and interleukin-1 beta (IL-1beta) in gingival crevicular fluid (GCF). METHODS: Eighteen patients, each of whom had 2 or more sites with probing depth measuring > 5 mm, were included this clinical trial. The 41 sites were randomly assigned treatment with either Nd:YAG laser alone (n = 14, 100 mj, 20 pps, 2.0 W, 120 seconds), CO2 laser alone (n = 13, 2.0 W, 120 seconds), or ultrasonic scaling alone (n = 14, maximum power, 120 seconds). At baseline and at 1, 4, and 12 weeks, clinical measurements (plaque index, PI; gingival index, GI; probing depth, PD; clinical attachment level, CAL; and bleeding on probing, BOP) were performed and subgingival plaque and GCF sampled. A quantitative analysis of Porphyromonas gingivalis was carried out using real-time polymerase chain reaction (PCR) procedures. The amounts of IL-1beta were estimated by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Decreased inflammation and PD were observed in all 3 groups after treatment. A microbiological analysis indicated significant decreases in P. gingivalis in the Nd:YAG and scaling groups at 1, 4, and 12 weeks compared to baseline (P < 0.05). The amount of GCF significantly decreased in the Nd:YAG and scaling groups at 12 weeks. The amount of IL-1beta increased in the CO2 group from baseline to 1 week (P < 0.05). The Nd:YAG group tended to show a decrease in IL-1beta from 1 to 12 weeks, although these data were not statistically significant. CONCLUSIONS: Our data suggest that Nd:YAG laser and ultrasonic scaling treatments showed significant improvements regarding the clinical parameters and subgingival microflora compared to the baseline, but no significant difference was observed between the 3 groups.
Analysis of Variance↗
Association of interleukin-1 receptor antagonist gene polymorphisms with early onset periodontitis in Japanese.
BACKGROUND/AIMS: Early onset periodontitis (EOP), newly 'aggressive periodontitis', is considered to have genetic basis, which have not been clearly defined. The interleukin-1 (IL-1) gene cluster polymorphism as one of genetic factors may influence the expression of several chronic inflammatory diseases. The aim of this study is to investigate the frequency of single nucleotide polymorphisms (SNPs) in the genes encoding IL-1alpha, IL-1beta and a variable number of tandem repeat (VNTR) polymorphisms in the IL-1 receptor antagonist gene (IL-1RN) in 47 generalized EOP (G-EOP) patients and 97 periodontally healthy controls. MATERIAL AND METHODS: All subjects were of Japanese descent and systemically healthy. They were identified according to established clinical criteria. SNPs in the IL-1alpha (+ 4845) and IL-1beta (- 511, + 3954) genes were analyzed by amplifying the polymorphic region using polymerase chain reaction (PCR), followed by restriction-enzyme digestion and agarose gel electrophoresis. IL-1RN (VNTR) polymorphisms were then detected by PCR amplification and fragment size analysis. RESULTS: There was no significant difference in the IL-alpha (+ 4845) and IL-1beta (- 511, + 3954) genotypes and allele frequencies between G-EOP patients and healthy controls. However, the frequency of IL-1RN (VNTR) polymorphic alleles was found to be significantly increased in G-EOP patients (chi2 test, P = 0.007; odds ratio = 3.40). Additionally, the carriage rate of IL-1RN (VNTR) polymorphisms was significantly higher in G-EOP patients than in healthy controls (chi2 test, P = 0.005; odds ratio = 3.81). CONCLUSION: These findings suggest that IL-1RN (VNTR) polymorphisms are associated with G-EOP in Japanese.
Adult↗
Accumulation of human heat shock protein 60-reactive T cells in the gingival tissues of periodontitis patients.
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.
Adult↗
Vascular endothelial growth factor and transforming growth factor-alpha and -beta1 are released from human cultured gingival epithelial sheets.
BACKGROUND: It has been demonstrated that human cultured epithelial sheets prepared by tissue engineering techniques provide useful graft material for wound healing and tissue regeneration. However, limited information is available with regard to biological effects such as release of growth factors from human cultured gingival epithelial sheets (HCGES). The purpose of this study was to measure the levels of growth factors released from HCGES into culture medium. METHODS: Twenty patients aged 44 to 71 years with generalized chronic periodontitis were recruited, and their gingival tissues obtained during periodontal flap surgery. The levels of vascular endothelial growth factor (VEGF), transforming growth factor-alpha and -beta1 (TGF-alpha and -beta1), and epidermal growth factor (EGF) released into the culture medium were determined using enzyme-linked immunosorbent assay at the just confluent (T1) and the adequate stratification (T2) culture stages. The medium without cells was collected as a control (T0). Statistical tests were performed by analysis of variance and Sheffé multiple range test among T0, T1, and T2. RESULTS: Significantly higher levels of VEGF and TGF-alpha were observed at T1 and T2 compared to T0 (P<0.001). In addition, there was a significant difference in the TGF-alpha levels between T2 and T1 (P<0.001). TGF-beta1 at T1 was significantly higher in comparison to T0 (P <0.01). EGF had been released only in a small amount at T2. CONCLUSION: This study indicates that meaningful amounts of VEGF and TGF-alpha and -beta1 are released from HCGES, which suggests potential for promoting wound healing and tissue regeneration after grafting.
3T3 Cells↗