Biomedical subjects

H Yoshie

Publications and source records attributed to H Yoshie.

At least 19 recordsLinked to original sources

PubMed2006

Increased infiltration of CD1d and natural killer T cells in periodontal disease tissues.

BACKGROUND: Natural killer T (NKT) cells are a unique T lymphocyte subset that has been implicated in the regulation of immune responses associated with a broad range of diseases including autoimmunity, infectious diseases, and cancer. In contrast to conventional T cells, NKT cells are reactive to major histocompatibility complex (MHC) class I-like molecule CD1d. Considering the periodontitis having both aspects of infection and autoimmunity in nature, CD1d and reactive NKT cells are of particular importance. OBJECTIVE: The aim of the present study was to examine whether the expression of CD1 isoforms and Valpha24(+) invariant NKT cells is associated with different disease entities, namely gingivitis and periodontitis. MATERIAL AND METHODS: Immunohistochemical analysis was performed on cryostat sections of gingival tissues from 19 patients with periodontitis and eight patients with gingivitis using antibodies to CD1a, b, c, d, Valpha24(+) invariant NKT cells, CD83, CD3 and CD19. RESULTS: Although all four subsets of CD1 molecules were expressed in periodontal lesions, CD1d was most abundant. CD1d expression was more frequent in periodontitis than gingivitis and increased together with increase of invariant NKT cell infiltration. Double immunohistochemical staining showed co-expression of CD1d and CD19 on identical cells and proximate infiltration of CD1d(+) and invariant NKT cells. CONCLUSION: These findings suggest that CD1d-expressing B cells could activate NKT cells by CD1d-restricted manner and this NKT cell activation may play roles in pathogenesis of periodontal diseases.

Adult↗

PubMed2005

Interleukin-6 (IL-6)--373 A9T11 allele is associated with reduced susceptibility to chronic periodontitis in Japanese subjects and decreased serum IL-6 level.

We investigated whether interleukin-6 (IL-6) gene polymorphisms could be associated with chronic periodontitis (CP) and serum IL-6 level. One hundred and twelve CP and 77 non-CP Japanese subjects were analyzed for IL-6 -597 (G/A), -572 (C/G), -373 (A(n)T(m)), -190 (C/T), and -174 (G/C) polymorphisms. We could only detect -572 and -373 polymorphisms and found that the frequency and carriage rate of the -373 A9T11 allele were significantly higher in non-CP subjects. Enzyme-linked immunosorbent assay confirmed that the -572 and -373 G[A9T11] haplotypes were associated with lower serum IL-6 level. These findings suggest that IL-6 -373 A9T11 allele could be associated with reduced susceptibility to CP among Japanese subjects and decreased serum IL-6 level.

Alleles↗

PubMed2005

Effects of Porphyromonas gingivalis antigens and proinflammatory cytokines on human coronary artery endothelial cells.

OBJECTIVE: Individuals with periodontitis have been cited as having a significantly increased risk of developing coronary heart disease. Although accumulating evidence suggests that periodontal infection is involved in the development and progression of atherosclerosis, the underlying mechanisms remain to be elucidated. In the present study, we examined how periodontal infection could contribute to endothelial dysfunction. METHODS: Human coronary arterial endothelial cells were stimulated with tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, both of which are reported to be elevated in the serum of periodontitis patients. Cells were also stimulated with lipopolysaccharide, outer membrane protein and heat shock protein 60 derived from Porphyromonas gingivalis, a representative periodontopathic bacterium which is known to stimulate myeloid cells. RESULTS: Although TNF-alpha and IL-1beta, at concentrations a little higher than those in sera of periodontitis patients, up-regulated the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, P. gingivalis antigens had only a slight stimulatory effect. CONCLUSION: Experiments in which the total pathogen burden is considered, rather than a single species of bacteria, would increase our understanding of the contribution of which periodontal infection to atherogenesis.

Antigens, Bacterial↗

PubMed2005

Alpha 2 integrin +807 polymorphism in drug-induced gingival overgrowth.

Alpha2 integrin on fibroblasts is reported to play an important role in the induction of drug-induced gingival overgrowth, which is characterized by excessive accumulation of type I collagen in gingival connective tissue. Silent polymorphism 807 T/C within the alpha2 integrin gene is associated with high/low alpha2 integrin expression. The aim of this study was to test the hypothesis that expression of alpha2 integrin 807 T/C polymorphism correlates with drug-induced gingival overgrowth. A case-control study comparing 136 subjects taking calcium channel blockers (72 with vs. 64 without drug-induced gingival overgrowth) demonstrated that the frequency of the +807 C allele was significantly higher in the case group than in the controls (odds ratio, 3.61; 95% confidence interval, 2.14 - 6.10; P < 0.05). The present findings suggest that the alpha2 +807 C allele is one of the genetic risk factors for drug-induced gingival overgrowth.

Adolescent↗

PubMed2004

Polymorphisms in the IL-6 receptor (IL-6R) gene: strong evidence that serum levels of soluble IL-6R are genetically influenced.

We have investigated the association of the recently identified IL6R polymorphisms with the serum levels of soluble IL-6 receptor (sIL-6R). sIL-6R is generated by shedding of the membrane-bound receptor (IL-6Ralpha) or alternative mRNA splicing. In total, 115 healthy volunteers were genotyped, with 70 of them analyzed for sIL-6R levels. Using the PCR/RFLP methods, two important polymorphic sites were selected for genotyping: the 48892A/C (D358A) in exon 9 and the -183G/A in the promoter region. In exon 9, C allele carriers had higher sIL-6R level (P<0.0001) showing that this sequence variation, which corresponds to the proteolytic cleavage site of IL-6Ralpha, strongly influences the serum sIL-6R levels. In the promoter region, G allele carriers had lower sIL-6R levels (P<0.0082) compared with the A allele carriers. This could be attributed to the linkage disequilibrium (D'=0.54, chi2=51.3, P<0.0001) between the -183G/A and the 48892A/C gene polymorphisms.

Adult↗

PubMed2004

A novel polymorphism of FcalphaRI (CD89) associated with aggressive periodontitis.

Immunoglobulin A Fc receptor (FcalphaRI) has been implicated in the pathogenesis of periodontitis, because increased IgA responses and FcalphaRI-bearing neutrophils are observed in the disease lesions. Inter-individual differences in susceptibility to periodontitis may be attributable to genetic variability in FcalphaRI-mediated immunity. We here identified an FcalphaRI novel polymorphism (nt 324 A-to-G transition) in the membrane-distal extracellular domain encompassing the ligand-binding site, not resulting in an amino acid change. We compared the FcalphaRI genotype distributions among 46 Japanese aggressive periodontitis (AGP) patients, 80 race-matched healthy controls (HCs), and 59 Caucasian HCs. No ethnic differences were observed in the FcalphaRI genotype distributions between Japanese and Caucasian HC. Notably, we observed a difference in the genotype distribution between the AGP and HC groups. Carriage rate of the nt 324 A allele was higher in the AGP (65.2%) than that in the HC group (42.5%) (odds ratio 2.54). Polymorphonuclear neutrophils from peripheral blood and gingival crevicular fluid exhibited a decreased phagocytosis of periodontopathic bacteria (Porphyromonas gingivalis) in the nt 324 A/A patients as compared with the nt 324 G/G patients. These results document a genetic polymorphism at the FcalphaRI ligand-binding site to be associated with susceptibility to AGP.

Adult↗

PubMed2004

T-cell clonality to Porphyromonas gingivalis and human heat shock protein 60s in patients with atherosclerosis and periodontitis.

Individuals with periodontitis have been reported to have a significantly increased risk of developing coronary heart disease. Several studies have demonstrated that the immune response to heat shock protein 60 (HSP60) may be involved in the pathogenesis of both atherosclerosis and chronic periodontitis. To investigate this possible link between these diseases, cellular and humoral immune responses to HSP60 in atherosclerosis patients were compared with those in periodontitis patients and healthy subjects using human and Porphyromonas gingivalis HSP60 (GroEL) as antigens. Antibody levels to both human and P. gingivalis HSP60s were the highest in atherosclerosis patients, followed by periodontitis patients and healthy subjects. Clonal analysis of the T cells clearly demonstrated the presence of not only human HSP60- but also P. gingivalis GroEL-reactive T-cell populations in the peripheral circulation of atherosclerosis patients. Furthermore, these HSP60-reactive T cells seemed to be present in atherosclerotic lesions in some patients. These results suggest that T-cell clones with the same specificity may be involved in the pathogenesis of the different diseases.

Adult↗

PubMed2004

Interleukin-4 gene polymorphisms in Japanese and Caucasian patients with aggressive periodontitis.

OBJECTIVES: Recently, interleukin (IL) 4 gene polymorphisms have been analyzed in association with periodontitis. Genetic differences between Caucasian and Japanese patients with periodontitis have previously been detected. The aim of the present study was to analyze IL-4 genotypes in Caucasian and Japanese patients with aggressive periodontitis (AgP). MATERIAL AND METHODS: One hundred and twenty-four subjects were included in the study, 31 Japanese and 30 Caucasian patients with generalized AgP, plus 30 Japanese and 33 Caucasian healthy controls. IL-4 polymorphisms were determined by polymerase chain reaction. A logistic regression was used to investigate the possible association of the genotypes with the disease in both populations. Odds ratio (OR) estimates were analyzed for allele frequencies. RESULTS: No significant association of IL-4 polymorphisms with the risk of AgP was determined in either population. However, the allele frequencies showed different results between populations. The carriage of the polymorphism in intron 2 was higher in Caucasian patients compared with controls (OR: 2.0, 95% confidence interval: [1.0;4.2]. Furthermore, the frequency of the IL-4 promoter/intron 2 composite genotype (PP+/IP+) in patients and controls, respectively, was found to be approximately 25% and 60% higher in the Japanese population than in the Caucasian population. CONCLUSION: There was no evidence of an association of IL-4 genotypes and AgP in either population, although the frequencies of the IL-4 genotypes in the Japanese and the Caucasians were different.

Adult↗

PubMed2003

Porphyromonas gingivalis antigen preferentially stimulates T cells to express IL-17 but not receptor activator of NF-kappaB ligand in vitro.

Although T cells have been implicated in the pathogenesis and are considered to be central to both their progression and control of chronic inflammatory periodontal diseases, the precise contribution of T cells to tissue destruction has not been fully clarified. Recently, interleukin (IL)-17 and receptor activator of Nuclear factor kappaB NF-kappaB ligand (RANKL) have received much attention as a result of their proinflammatory and bone metabolic roles, respectively. We therefore investigated the effect of outer membrane protein (OMP) from Porphyromonas gingivalis (P. gingivalis) on the expression of IL-17 and RANKL in peripheral blood mononuclear cells (PBMCs) and compared these between gingivitis and periodontitis, which are representative of stable and progressive lesions, respectively. The in situ expression of these molecules was also examined. P. gingivalis OMP stimulated PBMCs to express IL-17 at both the mRNA and protein level. Although the mean expression of mRNA was not different between the two groups, the mean level of IL-17 in the culture supernatants was higher in gingivitis patients than in periodontitis patients. However, the frequency of IL-17-positive samples was higher in the periodontitis patients. This stimulatory effect was not evident for RANKL expression in either periodontitis or gingivitis patients. In gingival tissue samples, IL-17 mRNA was detected in gingivitis more frequently than in periodontitis. The expression of RANKL mRNA was much lower than that of IL-17 in terms of both level and frequency. These results suggest that IL-17 but not RANKL may be involved in the pathogenesis of periodontal diseases. However, there may be negative regulatory mechanisms for IL-17 in gingivitis.

Adult↗

PubMed2003

FcgammaRIIB gene polymorphisms in Japanese periodontitis patients.

Human type II low-affinity receptor for immunoglobulin G (FcgammaRII) constitutes a clustered gene family consisting of FcgammaRIIA, IIB and IIC genes. FcgammaRIIB is unique in its ability to transmit inhibitory signals in B cells via immunoreceptor tyrosine-based inhibitory motif (ITIM). B-cell activation and subsequent elevated production of IgG are the immunopathological features of inflammatory disease such as periodontitis. To determine whether an association with periodontitis susceptibility exists, genetic polymorphisms of FcgammaRIIB were examined in Japanese patients with aggressive periodontitis (AGP) and chronic periodontitis (CP), and in the race-matched healthy controls (HCs). A significant difference was observed in the distribution of FcgammaRIIB-232I/T allele (exon 5) between the AGP and HC groups, with enrichment of the 232T in the AGP group (P=0.006). In addition, the FcgammaRIIB-nt 646-184A/G allele (intron 4) distribution was significantly different between the CP and HC groups, with enrichment of the nt 646-184A in the CP group (P=0.011). These results document the association of FcgammaRIIB gene polymorphisms with susceptibility to periodontitis in the Japanese.

Adolescent↗

PubMed2003

Single-nucleotide polymorphism in the CD14 promoter and periodontal disease expression in a Japanese population.

It has been reported that there is a relationship between a single-nucleotide polymorphism (SNP) in the promoter region of the CD14 gene at position -159 (C-->T) and infectious diseases. The aim of the present study was to test the hypthesis that expression of this SNP correlates with periodontal disease in a Japanese population. The CD14 genotype was determined in 163 subjects with periodontitis and in 104 age- and gender-matched control subjects without periodontitis. The genotype distribution and allele frequency within the periodontitis patients were not significantly different from those of control subjects. There was, however, a significant difference in the genotype distribution between young patients (< 35 yrs) and older patients (>/==" BORDER="0"> 35 yrs). These findings suggest that CD14 -159C/T polymorphism is not related to the development of periodontitis in a Japanese population, but that, within the periodontitis subjects, expression of the SNP may be related to early disease activity.

Adult↗

PubMed2003

T cell regulation of the immune response to infection in periodontal diseases.

Although T cells have been implicated in the pathogenesis and are considered to be central both in progression and control of the chronic inflammatory periodontal diseases, the precise contribution of T cells to the regulation of tissue destruction has not been fully elucidated. Current dogma suggests that immunity to infection is controlled by distinct T helper 1 (Th1) and T helper 2 (Th2) subsets of T cells classified on the basis of their cytokine profile. Further, a subset of T cells with immunosuppressive function and cytokine profile distinct from Th1 or Th2 has been described and designated as regulatory T cells. Although these regulatory T cells have been considered to maintain self-tolerance resulting in the suppression of auto-immune responses, recent data suggest that these cells may also play a role in preventing infection-induced immunopathology. In this review, the role of functional and regulatory T cells in chronic inflammatory periodontal diseases will be summarized. This should not only provide an insight into the relationship between the immune response to periodontopathic bacteria and disease but should also highlight areas of development for potentially new therapeutic modalities.

Animals↗

PubMed2002

Oligoclonal accumulations of T-cell clones in gingivitis and periodontitis lesions.

Gingivitis and periodontitis have distinct clinical and immunopathological characteristics. We have previously demonstrated that T cells infiltrating periodontitis lesions recognize a restricted repertoire of antigens or antigenic epitopes. However, the clonality of T cells in the gingivitis lesion is not known. Therefore, we carried out a clonal analysis of T cells infiltrating gingivitis lesions using combined reverse transcription-polymerase chain reaction and single-strand conformation polymorphism (SSCP) analysis. As with periodontitis lesions, SSCP analysis demonstrated the emergence of a number of distinct bands suggesting clonal accumulation in the gingivitis lesion. Although the mean number of distinct bands in gingival tissue was significantly higher than that in peripheral blood mononuclear cells, numerical analysis clearly demonstrated that there was no difference in the total number of bands in gingival tissue specimens between the different disease types. Although there were slight variations in the number of distinct bands in each Vbeta family, there was no significant difference between gingivitis lesions and periodontitis lesions. These results demonstrate that antigen-specific T-cell responses also take place in gingivitis lesions. It remains to be determined, however, what role these antigen-specific T cells play and what antigens the T cells recognize in the pathogenesis of periodontal disease.

Clone Cells↗

PubMed2002

Self-heat shock protein 60 induces tumour necrosis factor-alpha in monocyte-derived macrophage: possible role in chronic inflammatory periodontal disease.

Heat shock protein 60 (hsp60) has been increasingly recognized as an important molecule in infectious and autoimmune diseases. We have demonstrated previously that serum antibodies to both human hsp60 and Porphyromonas gingivalis GroEL were elevated in periodontitis patients compared with healthy subjects. In order to clarify the relative importance of hsp60 in the inflammatory response in periodontal disease, the stimulatory effect of human and bacterial hsp60 on the production of tumour necrosis factor-alpha (TNF-alpha) was examined in phorbol myristate acetate (PMA)-stimulated THP-1 cells. As bacterial hsp60s, recombinant P. gingivalis and Actinobacillus actinomycetemcomitans GroEL was used. Human hsp60 but not P. gingivalis or A. actinomycetemcomitans GroEL demonstrated stimulatory activity similar to lipopolysaccharide (LPS) derived from the bacteria. The activity of hsp60 was inhibited by anti-CD14 and anti-Toll-like receptor 4 (TLR4) antibodies, suggesting that both CD14 and TLR4 mediate hsp60 signalling. Immunohistochemical analysis demonstrated that hsp60 is abundantly expressed in periodontitis lesions. Therefore, it is postulated that periodontopathic bacteria stimulate the cells in the periodontium to up-regulate the expression of hsp60, which in turn may stimulate macrophage and possibly other cells to produce proinflammatory cytokines. These mechanisms may be involved in the chronicity and tissue destruction of periodontal disease.

Carcinogens↗

PubMed2001

Elevated proportion of natural killer T cells in periodontitis lesions: a common feature of chronic inflammatory diseases.

Although periodontitis is a chronic inflammatory disease caused by a group of so-called periodontopathic bacteria, autoimmune mechanisms have also been implicated in the disease process. Recently, a unique subset of lymphocytes designated natural killer (NK) T cells expressing the Valpha24JalphaQ invariant T cell receptor (TCR) has been reported to have a regulatory role in certain autoimmune diseases. Therefore, we investigated the proportion of the invariant Valpha24JalphaQ TCR within the Valpha24 T cell population in periodontitis lesions and gingivitis lesions using single-strand conformation polymorphism methodology. NK T cells were identified with a specific JalphaQ probe whereas the total Valpha24 TCR was identified using an internal Calpha probe. NK T cells were a significant proportion of the total Valpha24 population both in periodontitis lesions and to a lesser extent in gingivitis lesions but not in the peripheral blood of either periodontitis patients or nondiseased controls. Using immunohistochemistry, some of Valpha24(+) cells in the periodontitis lesions seemed to associate with CD1d(+) cells, which are specific antigen-presenting cells for NK T cells. Although the mechanism underlying the elevation of NK T cells in periodontitis and in gingivitis lesions remains unclear, it can be postulated that NK T cells are recruited to a play regulatory role in the immune response to bacterial infection.

Adult↗

PubMed2001

Evidence for a novel polymorphism affecting both N-linked glycosylation and ligand binding of the IgG receptor IIIB (CD16).

Immunoglobulin G Fc receptor IIIb (FcgammaRIIIb) is constitutively expressed on neutrophils, and has three allelic forms: FcgammaRIIIb-NA1, FcgammaRIIIb-NA2, and FcgammaRIIIb-SH. We identified two Japanese subjects in whom an A to G substitution at nt 221 changes asparagine (N) to serine (S) at amino acid position 45 in the FcgammaRIIIb-NA2 gene. FcgammaRIIIb-NA2-specific monoclonal antibodies (GRM1 and PEN1) did not bind to mutant neutrophils, which lack an N-linked glycosylation site. Furthermore, IgG3-mediated neutrophil phagocytosis by mutant was slightly increased as compared to wild-type donors (Note).

Amino Acid Sequence↗

PubMed2001

Seven single nucleotide substitutions in human Fc(gamma) receptor IIB gene.

Variation screening for the immunoglobulin G Fc receptor IIB (Fc(gamma)RIIB) gene was performed with the genomic DNA from 100 healthy Japanese subjects. We identified 3 non-synonymous and 2 synonymous substitutions and 2 single-nucleotide polymorphisms in an intron region. These substitutions were found to be located in the ligand-binding domain and the intron, which might alter the function of Fc(gamma)RIIb.

Amino Acid Motifs↗

PubMed2001

Characterization of serum antibody to Actinobacillus actinomycetemcomitans GroEL-like protein in periodontitis patients and healthy subjects.

Recent evidence suggests that molecular mimicry between bacterial and human heat shock protein 60 (hsp60) is involved in various conditions of autoimmune and infectious diseases. Many periodontopathic bacteria have been reported to express GroEL-like protein that is homologous to human hsp60. In this study, the presence of antibodies to the hsp60 of Actinobacillus actinomycetemcomitans in the sera of periodontitis patients and periodontally healthy control subjects was evaluated by enzyme-linked immunosorbent assay using a recombinant A. actinomycetemcomitans GroEL as an antigen. Furthermore, their cross-reactivity with Escherichia coli GroEL and Mycobacterium bovis BCG hsp65 was examined. The mean values of antibody were 0.624 (range 0.088-1.113) and 0.728 (range 0.217-1.296) in control subjects and periodontitis patients, respectively. The antibody levels to A. actinomycetemcomitans after absorption with E. coli GroEL and M. bovis BCG clearly decreased in both control subjects and periodontitis patients. The remaining antibody levels to A. actinomycetemcomitans GroEL after absorption with M. bovis BCG hsp65 were higher than those with E. coli GroEL, indicating higher cross-reactivity with E. coli GroEL. These results suggest that not only periodontitis patients but also periodontally healthy subjects may be infected with A. actinomycetemcomitans but that the part of the antibody could be derived from the cross-reactivity with E. coli GroEL. Any relationship of the antibody to the disease, however, remains to be determined.

Adult↗