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Background: Toll-like receptors (TLRs) play pivotal roles in host immune responses and have been suggested to be involved in the development of many infectious diseases. In this study, the mRNA expression levels of TLR2, TLR4, and TLR9 and their relationship with periodontopathic bacteria in periodontal tissue are examined. Furthermore, the mechanism of TLR induction by Porphyromonas gingivalis is investigated in human gingival fibroblasts (HGFs). Methods: Gingival tissue and subgingival plaque samples were collected from 19 patients with chronic periodontitis (CP) and 16 control individuals without periodontitis. Gene expression levels in the tissues and in HGFs were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The numbers of periodontopathic bacteria were determined by quantitative real-time PCR. Results: The expression levels of TLR2 and TLR9 were significantly higher in the tissues of patients with CP compared to the tissues of control individuals. The mRNA levels of TLR2 and TLR9, but not TLR4, were positively correlated with the number of P. gingivalis in subgingival plaque. P. gingivalis sonicated extract, P. gingivalis lipopolysaccharide, P. gingivalis DNA, and tumor necrosis factor-αTNF could significantly upregulate the mRNA expression of TLR2 in HGFs. Furthermore, P. gingivalis-mediated TLR2 expression was suppressed by TNF-α antibody. Conclusions: This study suggests that P. gingivalis infection induces TLR2 and TLR9 upregulation patients with CP. P. gingivalis-induced TLR2 expression in HGFs is partially dependent on TNF-α and may lead to sensitization of HGFs to bacterial components encountered in the periodontal microenvironment. [ABSTRACT FROM AUTHOR]

Periodontal regeneration using EDTA or PDGF showed promising results, but the effect of combined application was still unclear. This study aimed to verify the effect of EDTA and/or PDGF application on root adhesion and proliferation of PDL fibroblast cells. Eighty specimens were prepared from forty periodontitis teeth and made five groups: (1) diseased (untreated), (2) SRP (scaling root planing), (3) EDTA (24%), (4) PDGF (25 ng/ml) and (5) Combined application of EDTA and PDGF. Periodontal ligament cells were cultured on the above conditioned dentin plate, and SEM examination was preformed and cells were counted within a representative standard area for both cell morphology and density. All groups including untreated showed significantly increase of adhered cells from baseline to 7 days. Among them, rate of increase was much higher in EDTA, PDGF, and combined groups. ANOVA test indicated that the number of cells in PDGF and combined groups was significantly higher than diseased group at 1 day. On day 7, PDGF and combined groups showed significantly higher number of adhesion cells than that found in the diseased, SRP and EDTA groups. Thus, root conditioning with EDTA enhanced cell adhesion more than SRP alone. There was no significant difference of cell number between PDGF and combined group. Combined application of EDTA and PDGF increased significantly PDL cell adhesion than EDTA alone. PDGF alone, however, also showed comparable effect to combined application at all periods. Thus, synergistic effect between PDGF and EDTA was not observed. [ABSTRACT FROM AUTHOR]

El artículo trata el rol de la ciclooxigenasa 2 y la prostaglandina E2 en la enfermedad periodontal. Nota que las prostaglandinas hacen un papel en la patogenia de las enfermedades periodontales. Menciona que se implica COX-2 en la producción de prostaglandinas en la enfermedad periodontal. Afirma que se necesitan estudios sobre PGEα, PGF, PGI2 y otras prostaglandinas para comprender mejor el efecto de las prostaglandinas en la enfermedad periodontal.

The article discuses the roles of receptor activator of nuclear factor-kB ligand (RANKL) and osteoprotegerin in periodontology. The article details some topics of periodontal health and disease such as the immune system in the gingival tissue, diagnostic value of antibacterial antibodies in periodontitis, vaccine against periodontitis, osteoimmunology, expression and role of RANKL in some diseases. The article concludes with a note on further research in molecular mechanisms in periodontology.

Introduction: The aim of this study was to compare serum antibody responses to periodontal pathogens after single-visit full-mouth ultrasonic debridement and quadrant-wise therapy. Material and Methods: Thirty-six subjects with chronic periodontitis were randomized into three groups: quadrant-wise debridement in four visits, one-visit full-mouth debridement with water and with povidone iodine. Blood samples were collected before and immediately after treatment and 1, 3 and 6 months post-therapy. Serum antibody titres and avidity to Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia and Treponema denticola were determined by enzyme-linked immunosorbent assay (ELISA) and thiocyanate ELISA, respectively. Results: IgG titres to P. gingivalis significantly decreased at 1, 3 and 6 months in full-mouth debridement with water group, while significant reductions were seen only at 3 and 6 months after quadrant-wise debridement. Both full-mouth groups showed significant reduction in IgG titres to A. actinomycetemcomitans at 3 and 6 months. Significant increases in antibody avidity to P. gingivalis and A. actinomycetemcomitans were noted 3 months following full-mouth debridement with povidone. Conclusion: Both full-mouth and quadrant treatments generally resulted in a decrease in antibody titres and increase in antibody avidity. Full-mouth debridement induced an earlier reduction of IgG titre to P. gingivalis and A. actinomycetemcomitans, than quadrant-wise therapy. [ABSTRACT FROM AUTHOR]

Background: Papillon Lefevre syndrome (PLS) is a rare autosomal recessive disorder characterized by pal mar-plantar hyperkeratosis and rapid periodontal destruction of both primary and permanent dentitions. It has been shown that the disease is caused by cathepsin C gene (CTSC) mutation leading to the deficiency of cathepsin C enzymatic activity. This study demonstrates the clinical manifestations and CTSC mutational and enzymatic activity analyses in a 5-year-old Thai male PLS patient and his parents. Methods: Peripheral blood samples were obtained for genomic DNA isolation. All exons of the CTSC gene were amplified by polymerase chain reaction (PCR) using specific primers. Mutations were identified by DNA sequencing. Verification of the mutation was performed by digestion of PCR products by restriction endonucleases. The cathepsin C enzymatic activity was determined using the synthetic substrate glycyl-L-arginine-7-amino-4-methylcoumarin. Results: The patient demonstrated classical characteristics of PLS, including hyperkeratotic skin lesions. By the age of 5, all of his primary teeth were extracted due to severe periodontal infection. The parents had no physical abnormalities. The periodontal examination revealed localized mild periodontal destruction. Sequence analysis showed a nucleotide change at position 90 from C>A (c.90C>A) which resulted in a change from cysteine residue to a premature stop codon at the amino acid position 30 in the exon 1. The HpyCH4V digestion revealed that the patient was homozygous, whereas both the father and mother were heterozygous carriers of this mutation. The cathepsin C activity was reduced in the patient's mother, and the activity in the patient was almost completely lost. Conclusions: This is the first study to demonstrate a CTSC gene mutation in a Thai family with PLS, The identified mutation is novel and potentially leads to the drastic reduction of the cathepsin C enzymatic activity. This suggests that the mutation is pathogenetic, causing the PLS. Mutational analysis in more members of the family is warranted to identify whether the mutation is inherited from a common ancestor. [ABSTRACT FROM AUTHOR]

Umeda M, Miwa Z, Takeuchi Y, Ishizuka M, Huang Y, Noguchi K, Tanaka M, Takagi Y, Ishikawa I. The distribution of periodontopathic bacteria among Japanese children and their parents. J Periodont Res 2004; doi: 10.1111/j.1600-0765.2004.00754.x© Blackwell Munksgaard 2004It is not well known how periodontopathic bacteria colonize in the oral cavity during childhood. The purpose of this study was to investigate the distribution of periodontopathic bacteria in oral cavities of children and their parents and the relationship between the bacterial findings and clinical parameters.Fifty-six children (mean age: 8.3 ± 3.5, range: 1–15 years), including 15 with deciduous dentition, 26 with mixed dentition and 15 with permanent dentition, and their parents participated in this study. Whole saliva and dental plaque of the children and whole saliva of their parents were collected for detection of seven species of periodontopathic bacteria (Actinobacillus actinomycetemcomitans,Tannerella forsythensis(Bacteroides forsythus),Campylobacter rectus,Porphyromonas gingivalis,Prevotella intermedia,Prevotella nigrescensandTreponema denticola) using the polymerase chain reaction method. Clinical parameters including simplified Oral Hygiene Index and Papillary-Marginal-Attachment Index were recorded for the children and their accompanied parents.The detection frequencies ofT. forsythensis,C. rectus,P. nigrescens,T. denticola,A. actinomycetemcomitans and P. gingivalisin the oral cavities of children were 42.9%, 94.6%, 42.9%, 48.2%, 1.8% and 8.9%, respectively.T. forsythensis,P. gingivalisandT. denticolawere detected more frequently in the saliva of parents (54.8%, 54.8%, 88.1%, respectively) than in the saliva of children (25.5%, 7.3%, 41.8%, respectively). Different detection frequencies ofP. nigrescenswere found among the oral cavities of children with deciduous, mixed and permanent dentitions. In mixed dentition, females harboredT. forsythensismore frequently than males did. Children who harboredT. forsythensis,P. intermedia,P. nigrescensandT. denticolashowed high scores for oral debris measurement by simplified Oral Hygiene Index.T. forsythensis,P. intermediaandP. nigrescenswere detected more frequently in children whose parents were positive for these pathogens than in children whose parents were negative.High plaque retention seems to promote the colonization of periodontal pathogens in the oral cavities of children.T. forsythensis,P. intermediaandP. nigrescenswere detected more frequently in the oral cavities of children whose parents already harbored these bacteria. Familial transmission of these bacteria is suggested. [ABSTRACT FROM AUTHOR]

It is now beyond question that dental plaque is the main etiologic factor in the pathogenesis of periodontal diseases. However, recent advances have modified concepts regarding the etiology of these diseases. Several other aspects including genetic, host and environmental factors modulate the course of periodontal infections and this information has directed periodontal research into many basic, but complicated, mechanisms at molecular and cellular levels. The role of microorganisms in initiation and progression of periodontal infections was confirmed by numerous studies conducted over the years.

Nakamura T, Nitta H, Ishikawa I. Effect of low dose Actinobacillus actinomycetemcomitans lipopolysaccharide pretreatment on cytokine production by human whole blood. J Periodont Res 2004; 39; 129–135. © BlackwellMunksgaard, 2004 Periodontal disease is known to influence the systemic condition in various ways, and the bacteria and their products, such as lipopolysaccharides (LPS), may spread from periodontal lesions via the systemic circulation to affect distant organs. The level of LPS in plasma from such patients is reported to be very low, and this low level of LPS is suspected to have priming or desensitizing effect. Thus, we investigated the effects of low dose LPS pretreatment on LPS-dependent cytokine production by whole blood cells ex vivo. Blood samples obtained from seven systemically and periodontally healthy individuals were pretreated with or without 5 pg/ml Actinobacillus actinomycetemcomitans LPS, followed by further stimulation with 1 ng/ml A. actinomycetemcomitans LPS. The concentrations of interleukin-1 beta (IL-1β), IL-6, IL-10 and tumor necrosis factor-alpha (TNF-α) in the culture supernatants were then determined using enzyme-linked immunosorbent assay (ELISA). In addition, intracytoplasmic cytokine staining of whole blood cells was performed for flow cytometry. Pretreatment with 5 pg/ml A. actinomycetemcomitans LPS significantly enhanced the production of IL-1β and IL-6 from whole blood when further induced by 1 ng/ml LPS (1.72 times higher for IL-1β, 2.18 times higher for IL-6 than without pretreatment). The pretreatment did not enhance the production of either TNF-α or IL-10. Intracytoplasmic staining showed that the monocyte fraction was primarily involved in producing IL-1β and IL-6. Flow cytometric analysis revealed that pretreatment increased the number of IL-1β and IL-6 producing cells as well as mean fluorescence intensity of the stained cells. A low dose of bloodstream LPS found in periodontitis patients appears to be sufficient to prime monocytes, and may be capable of affecting the systemic responses of immune and inflammatory cells. [ABSTRACT FROM AUTHOR]

Background: As periodontal tissues are constantly exposed to mechanical stress during mastication, the relationship between mechanical stimulation and biochemical phenomena has been extensively investigated. Objectives: The aim of the present study was to assess the change in the production of angiogenic regulators produced by human gingival fibroblasts (HGF) and periodontal ligament fibroblasts (HPLF), cultured on a flexible substrate, before and after application of cyclic tensile stretching. Materials and methods: Both cell types were stretched in a Flexercell Strain Unit to 7, 14 and 21% elongation, at a frequency of 12 cycles/min. Medium cultured with HGF or HPLF was examined by enzyme-linked immunosorbent assay (ELISA) for vascular endothelial growth factor (VEGF), Western blotting of pigment epithelium-derived factor (PEDF) and in vitro angiogenesis assay. The residual cells were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) for both VEGF and PEDF mRNA expression. Results: Stretching increased the VEGF mRNA level and VEGF secretion in both HGF and HPLF. The concentration of VEGF in the conditioned medium of the stretched HPLF was almost the same as that of stretched HGF. In the in vitro angiogenesis assay, the conditioned medium of HPLF after stretching showed a dramatic increase in tube formation. In contrast, stretched HGF did not show enhanced tube formation, despite the increase in VEGF secretion by stretched HGF. The mRNA levels of PEDF, an inhibitor of angiogenesis, were higher in HGF than HPLF. The protein level of PEDF in HGF was also higher than that in HPLF. Conclusion: These findings suggest that under mechanical stress HPLF promotes angiogenesis via expression of VEGF, whereas under the same conditions angiogenesis is not promoted in HGF, due to the expression of PEDF. [ABSTRACT FROM AUTHOR]

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 shosed that stimulation with different periodontopathic bacteria, that included Porphyromonas gingivalis, Actinobacillus actimycetemcomitans, Prevotella intermedia, and Actinomyces viscosus, upregulated both CD86 and CD83 expression of 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 inteferon 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 suggests, therefore, that infiltrated gingival B cells have a possible role as APCs in the regulation and maintenance of local T cell response in periodontitis. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to identify Treponema socranskii in addition to Treponema denticola and Porphyromonas gingivalis by polymerase chain reaction (PCR), and to clarify the relationship between the presence of these microorganisms and the severity of clinical periodontal parameters. Methods: Saliva and subgingival plaque collected from 123 subjects (38 aggressive periodontitis patients, 65 chronic periodontitis patients, 20 healthy patients) were subjected to PCR to detect the aforementioned 3 microorganisms. Results: Detection frequencies of T. socranskii, T. denticola, and P. gingivalis in plaque samples from aggressive periodontitis patients (71.1%, 73.7%, 84.2%, respectively) and chronic periodontitis patients (89.2%, 93.8%, 95.3%) were much higher than those from healthy subjects (30%, 5.0%, 10.0%). In aggressive and chronic periodontitis patients, these 3 species of bacteria were detected frequently at sites that showed deep periodontal pockets and severe attachment loss. The percentage of these bacteria-positive sites increased as the gingival index score of chronic periodontitis patients increased. T. socranskii was frequently detected together with T. denticola or P. gingivalis at the same sites, and coexistence of these microorganisms was frequently observed in deep periodontal pockets of aggressive periodontitis patients. Conclusions: T. socranskii, T. denticola, and P. gingivalis were frequently detected in periodontitis patients by PCR. The prevalence of these 3 microorganisms was correlated with various clinical parameters. Taken together, our findings suggest that T. socranskii, T. denticola, and P. gingivalis are associated with the severity of periodontal tissue destruction. [ABSTRACT FROM AUTHOR]

Prostaglandin F2α (PGF2α) is a bioactive lipid mediator which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF2α in periodontal lesions are poorly understood. In the present study, we investigated the effect of PGF2α on interleukin (IL)-6 production in human gingival fibroblasts(HGF). PGF2α-stimulated IL-6 production in a time- and concentration-dependent fashion. IL-1β and tumor necrosis factor α (TNFα), proinflammatory cytokines, induced IL-6 production in a time-dependent manner, and PGF2α synergistically enhanced IL-6 production induced by IL-1β and TNFα. IL-6 mRNA was expressed in PGF2α-stimulated HGF, and PGF2α increased IL-6 mRNA levels induced by IL-1β and TNFα. Fluprostenol, a selective FP receptor agonist, could mimic PGF2α-induced IL-6 production. Since FP receptors are coupled to elevation of intracellular calcium and activation of protein kinase C (PKC), the mechanism of IL-6 production by PGF2α was investigated using TMB-8, an inhibitor of Ca2+ mobilization from intracellular stores, and calphostin C, an inhibitor of PKC. TMB-8 significantly suppressed PGF2α-induced IL-6 production, whereas calphostin C showed a stimulatory effect on PGF2α-induced IL-6 production. From these data, we suggest that PGF2α upregulates IL-6 production through FP receptors in HGF, that PGF2α synergistically enhances IL-6 production in IL-1β- and TNFα-stimulated HGF, and that PGF2α-induced IL-6 production may be dependent on intracellular Ca2+ mobilization and be downregulated by PKC activation. PGF2α may be involved in the pathogenesis of periodontal disease by enhancing IL-6 levels in periodontal lesions. [ABSTRACT FROM AUTHOR]

Increasing attention has been paid to cell-based medicines. Many in vivo and in vitro studies have demonstrated the efficacy of stem cell transplantation for the regeneration of periodontal tissues over the past 20 years. Although positive evidence has accumulated regarding periodontal regeneration using stem cells, the exact mechanism of tissue regeneration is still largely unknown. This review outlines the practicality and emerging problems of stem cell transplantation therapy for periodontal regeneration. In addition, possible solutions to these problems and cell-free treatment are discussed. [ABSTRACT FROM AUTHOR]

Background: The expression of leukotoxin varies among Actinobacillus actinomycetemcomitans strains and is dependent in part on the structure of the ltx promoter region. Highly leukotoxic strains, characterized by a 530 base pair (bp) deletion within the ltx promoter, have been associated with juvenile periodontitis in the United States and Europe. In the present study, we analyzed the ltx promoter structure to elucidate whether A. actinomycetemcomitans from Japanese periodontitis patients exhibits the highly toxic phenotype. Methods: Forty-five A. actinomycetemcomitans strains, including 43 clinical isolates, the highly leukotoxic strain JP2, and a minimally leukotoxic strain 652 were used in the study. The ltx promoter structure was analyzed by polymerase chain reaction (PCR), with oligonucleotide primers focusing the ltx promoter region, and nucleotide sequencing. Leukotoxic activity was determined by trypan blue exclusion. Western blotting assay was performed to detect the level of leukotoxin polypeptide. Results: A 495 bp PCR product was amplified from JP2, a 1025 bp product from 652 and 41 of the clinical isolates, and a 1926 bp product from the remaining two clinical isolates (AaIS1, AaIS2). Sequencing of the 1926 bp PCR fragment showed that it was similar to that of strain 652 but contained an 886 bp region that was identified as an insertion sequence (IS). Both AaIS strains expressed high levels of leukotoxicity. similar to strain JP2. In addition, a mutant (AaIS-) that had lost the IS element expressed a significantly lower level of leukotoxicity compared with AaIS strains. Furthermore, the levels of leukotoxin polypeptide expressed by these strains were consistent with their whole cell leukotoxicity. Conclusions: A. actinomycetemcomitans clinical strains which were isolated from Japanese periodontitis patients do not possess the 530 bp ltx promoter deletion. The results of this study suggest that a high level of leukotoxin expression correlates with the insertion of the transposable DNA element. [ABSTRACT FROM AUTHOR]

Prostaglandin E2 (PGE2) exerts its biological actions via EP receptors, which are divided into 4 subtypes of EP1, EP2, EP3 and EP4. In the present study, we investigated whether PGE2 regulated intercellular adhesion molecule-1 (ICAM-1) expression in human gingival fibroblasts (HGF) stimulated with tumor necrosis factor-α (TNFα) and if so, which subtype(s) of PGE2 receptors was involved. Exogenous addition of PGE2 to HGF inhibited ICAM-1 expression elicited by TNFα in a concentration-dependent manner. Treatment of HGF with indomethacin, a cyclo-oxygenase inhibitor, had no effect on TNFα-elicited ICAM-1 expression, although indomethacin completely inhibited PGE2 production enhanced by TNFα. Next, we examined which subtype(s) of the 4 EP receptors modulated the ICAM-1 expression elicited by TNFα, using subtype-specific agonists and antagonists. 1 l-deoxy-PGE1, a selective EP2/EP4 agonist, inhibited TNFα-elicited ICAM-1 expression as potently as PGE2, while butaprost, a selective EP2 agonist, was somewhat less effective than PGE2. AH23848B, an EP4 antagonist, antagonized the inhibitory effect of TNFα-elicited ICAM-1 expression by PGE2. Suiprostone, an EP1/EP3 agonist, and ONO-AP-324, an EP3 agonist, were inert to TNFα-elicited ICAM-1 expression. As EP2 and EP4 receptors are linked to elevation of intracellular cyclic AMP (cAMP), the effect of dibutyryl cAMP and 8-bromo--cAMP, cAMP analogs, on TNFα-elicited ICAM-1 expression was examined. Both the agents downregulated ICAM-1 expression in TNFα-stimulated HGF. From these data, we suggest that PGE2 downregulates TNFα-induced ICAM-1 expression in HGF, via EP2 and EP4 receptors by cAMP-dependent signaling pathways, which may result in control of inflammatory and immunological responses in periodontal disease. [ABSTRACT FROM AUTHOR]

Prostaglandin F2α (PGF2α) is a bioactive lipid mediator, which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF2α in the disease are not well understood. In the present study, we investigated the effect of PGF2α on intercellular adhesion molecule-1 (ICAM-1) expression in human gingival fibroblasts (HGF) and the effect of PGF2α on ICAM-1 expression elicited by proinflammatory cytokines, interferon-γ (IFN-γ) and tumour necrosis factor α (TNF α) in the cells. PGF2α-stimulated HGF expressed ICAM-1 expression in a time- and dose-dependent manner. IFN-γ-elicited ICAM-1 expression was synergistically increased by PGF2α, whereas TNF α-induced ICAM-1 expression was slightly inhibited by PGF2α. Fluprostenol, a selective FP receptor agonist, could mimic PGF2α-induced effect on ICAM-1 expression. Furthermore, signal transduction for the regulation of ICAM-1 by PGF2α was investigated using N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), a calcium calmodulin antagonist, and 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C (PKC). W-7 and H-7, remarkably, suppressed PGF2α-induced ICAM-1 expression and synergistic increase of ICAM-1 expression by combination of PGF2α and IFN-γ, while IFN-γ-elicited ICAM-1 expression was only partially inhibited by W-7 and H-7. From these data, we suggest that PGF2α upregulates ICAM-1 expression in HGF and synergistically enhances IFN-γ-induced ICAM-1 expression through FP receptor by calcium calmodulin-dependent and PKC-dependent pathways. PGF2α may be involved in the pathology of periodontal disease by upregulating ICAM-1 expression in HGF. [ABSTRACT FROM AUTHOR]

The present study investigated the effect of prostaglandin (PG) &E2 and PGI2 on intercellular adhesion molecule-1 (ICAM-1) expression in interleukin-1β (IL-1β)-stimulated human gingival fibroblasts (HGF). IL-1β potently induced ICAM-1 expression in HGF and indomethacin, a cyclooxygenase inhibitor, enhanced ICAM-1 expression in the cells. These data showed that endogenous PGs generated by HGF stimulated with IL-1β downregulated ICAM-1 expression. IL-1β significantly increased the levels of PGE2 and, to a lesser extent, those of 6-keto-PGF1α (a stable metabolite of PG12) in the culture media of HGF. Indomethacin completely inhibited the production of PGE2 and 6-keto-PGF1α in IL-1β-stimulated HGF. Exogenous PGE2 and carbacyclin (a stable derivative of PGI2) in the presence of indomethacin dose-dependently suppressed ICAM-1 expression in IL-1β-challenged HGF. Since PGE2 and PGI2are known to elevate intracellular cyclic AMP (cAMP) levels, we examined the effect of dibutyryl cAMP, a cAMP analogue, and isobutylmethylxanthine, a phosphodiesterase inhibitor, on ICAM-1 expression. Both agents downregulated ICAM-1 expression in IL-1β-stimulated HGF. These results suggest that PGE2 and PG12 downregulate ICAM-1 expression in IL-1β-stimulated HGF through a cAMP-dependent mechanism and that intracellular cAMP elevation in HGF may control inflammatory and immune responses in periodontal disease. [ABSTRACT FROM AUTHOR]

Oral Actinobacillus actinomycetemcomitans strains are serologically classified into 5 distinct groups, a to e. We examined the distribution of Actinobacillus actinomycetemcomitans serotypes in apanese patients with periodontitis. A total of 157 Actinobacillus actinomycetemcomitans clinical isolates from diseased sites of 39 patients with periodontitis were serotyped by using serotype-specific rabbit antisera against Actinobacillus actinomycetemcomitans serotypes a, b, c, d and e strains. In the immunodiffusion assay, autoclaved extracts of 42, 6, 39, 9 and 41 Actinobacillus actinomycetemcomitans clinical isolates reacted with serotypes a, b, c, d and e antisera, respectively. Although 37 patients were infected with a serotype strain, 2 patients harbored 2 different serotype strains, b/e and b/untypeable. To establish a correlation between serotype and genotype of Actinobacillus actinomycetemcomitans clinical isolates from 2 patients who had different serotype strains, we used arbitararily primed polymerase chain reaction (AP-PCR) to fingerprint clinical islates of different serotypes. The AP-PCR genotypes among 4 clinical isolates (b/e and b/untypeable) were identical to that of Actinobacillus actinomycetemcomitans Y4 (serotype b), indicating the presence of multiple Actinobacillus actinomycetemcomitans serotypes which are genetically homogeneous in the periodontally diseased sites of patients with periodontitis. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Interactions between pathogens and host induce human disorders including periodontitis, disintegration of the tooth supporting tissues. Tannerella forsythia has been linked to the periodontitis and several cytopathic reagents have been found in the bacterium; however, its contribution to the disease remains unclear. Biochemical approach to explore the cytopathic effect revealed two distinct activities in T. forsythia (ATCC 43037) extract; one detaches adherent cells from substratum and another arrests cells at G2. An executor of former activity, forsythia detaching factor (FDF) was identified; its genomic sequence and peptidase activity revealed that FDF is a substantial form of putative PrtH; prtH gene was hypothetically identified directly from a DNA fragment of the bacterium and its native product has never been shown. Since FDF was found in the bacterial culture supernatant, its activity implies a contribution to the disintegration of tissues although the mechanism how FDF disturbs cellular anchors remains elusive. [Copyright &y& Elsevier]

Abstract: Background: Periodontal pathogens were frequently detected in the occluded arteries of Buerger disease patients, hence we hypothesized that the infection from periodontal pathogens may be associated with Buerger disease. Methods: We investigated periodontal status using various clinical parameters and serum IgG antibody levels against T. denticola, P. gingivalis, A. actinomycetemcomitans and P. intermedia in nineteen Buerger disease patients and fifteen control subjects. The results were statistically analyzed. Results: The prevalence of periodontitis and the percentages of probing sites with PD≥4 mm and CAL≥4 mm were significantly higher in the patient group (P <0.001, P =0.016, and P <0.001, respectively). Patients had significantly higher serum IgG titers against T. denticola, P. gingivalis and A. actinomycetemcomitans (P =0.002, P =0.039, and P =0.011, respectively). Conclusions: This study provides evidence for possible implications of periodontitis in Buerger disease. [Copyright &y& Elsevier]