Publications (15) View all
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Article: Lipopolysaccharide of Aggregatibacter actinomycetemcomitans up-regulates inflammatory cytokines, prostaglandin E2 synthesis and osteoclast formation in interleukin-1 receptor antagonist-deficient mice.
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ABSTRACT: BACKGROUND AND OBJECTIVE: The interleukin (IL)-1 receptor antagonist (Ra) binds to IL-1 receptors and inhibits IL-1 activity. However, it is unclear whether the IL-1Ra plays a protective role in periodontal disease. The purpose of this study was to compare IL-1Ra knockout (KO) and wild-type (WT) mice in regard to proinflammatory cytokine production, osteoclast formation and bone resorption in response to periodontal bacterial lipopolysaccharide (LPS). MATERIAL AND METHODS: Peritoneal macrophages (Mφs) were obtained from 13-wk-old IL-1Ra KO and WT mice. Peritoneal Mφs were cultured with or without 10 μg/mL of Aggregatibacter actinomycetemcomitans LPS for 24 h. The levels of IL-1alpha (IL-1α), IL-1beta (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 were measured in periotoneal Mφs supernatant fluid (PM-SF) using an ELISA. Bone marrow cells were obtained from the mice and stimulated with PM-SF for 9 d, then stained with TRAP. The frequency of TRAP-positive multinucleated giant cell formation was calculated based on a fusion index. PM-SF-stimulated calvarial bone resorption was analyzed using micro-computed tomography, and calvarial histological analysis was performed using hematoxylin and eosin and TRAP staining. The expression of cyclooxygenase-2 (Cox2), prostanoid receptor EP4 (Ep4) and Rank mRNAs in bone marrow cells were measured using real-time quantitative PCR, while prostaglandin E2 (PGE2 ) production was determined by ELISA. RESULTS: The levels of IL-1α, IL-1β, TNF-α and IL-6 in IL-1Ra KO mice PM-SF stimulated with A. actinomycetemcomitans LPS were significantly increased by approximately 4- (p < 0.05), 5- (p < 0.05), 1.3- (p < 0.05) and 6- (p < 0.05) fold, respectively, compared with the levels in WT mice. Moreover, osteoclast formation, expression of Rank, Ep4 and Cox2 mRNAs and production of PGE2 were significantly increased by approximately 2- (p < 0.05), 1.6- (p < 0.05), 2.5- (p < 0.05), 1.6- (p < 0.05) and 1.9- (p < 0.05) fold, respectively, in IL-1Ra KO mice stimulated with A. actinomycetemcomitans LPS compared with WT mice. CONCLUSION: IL-1Ra regulates IL-1 activity and appears to reduce the levels of other inflammatory cytokines, including TNF-α and IL-6, while it also reduces expression of the EP4 receptor related to prostanoid sensitivity and osteoclast formation. These results suggest that IL-1Ra is an important molecule for inhibition of inflammatory periodontal bone resorption.Journal of Periodontal Research 04/2013; · 1.69 Impact Factor -
Article: Regulation of type 17 helper T-cell function by nitric oxide during inflammation.
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ABSTRACT: Type 17 helper T (Th17) cells are implicated in the pathogenesis many of human autoimmune diseases. Development of Th17 can be enhanced by the activation of aryl hydrocarbon receptor (AHR) whose ligands include the environmental pollutant dioxin, potentially linking environmental factors to the increased prevalence of autoimmune disease. We report here that nitric oxide (NO) can suppress the proliferation and function of polarized murine and human Th17 cells. NO also inhibits AHR expression in Th17 cells and the downstream events of AHR activation, including IL-22, IL-23 receptor, and Cyp1a1. Conversely, NO did not affect the polarization of Th17 cells from mice deficient in AHR. Furthermore, mice lacking inducible nitric oxide synthase (Nos2(-/-)) developed more severe experimental autoimmune encephalomyelitis than WT mice, with elevated AHR expression, increased IL-17A, and IL-22 synthesis. NO may therefore represent an important endogenous regulator to prevent overexpansion of Th17 cells and control of autoimmune diseases caused by environmental pollutants.Proceedings of the National Academy of Sciences 05/2011; 108(22):9220-5. · 9.68 Impact Factor -
Article: Azithromycin may inhibit interleukin-8 through suppression of Rac1 and a nuclear factor-kappa B pathway in KB cells stimulated with lipopolysaccharide.
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ABSTRACT: Recent studies have shown that the 15-member macrolide antibiotic azithromycin (AZM) not only has antibacterial activity, but also results in the role of immunomodulator. Interleukin (IL)-8 is an important inflammatory mediator in periodontal disease. However, there have been no reports on the effects of AZM on IL-8 production from human oral epithelium. Therefore, we investigated the effects of AZM on IL-8 production in an oral epithelial cell line. KB cells were stimulated by Escherichia coli or Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) lipopolysaccharide (LPS) with or without AZM. IL-8 mRNA and protein expression and production in response to LPS were analyzed by quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assay. The activation of nuclear factor-kappa B (NF-κB) and Rac1, which is important for IL-8 expression, was analyzed by enzyme-linked immunosorbent assay and Western blotting, respectively. IL-8 mRNA expression, IL-8 production, and NF-κB activation in LPS-stimulated KB cells were inhibited by the addition of AZM. LPS-induced Rac1 activation was also suppressed by AZM. This study suggests that AZM inhibits LPS-induced IL-8 production in an oral epithelial cell line, in part caused by the suppression of Rac1 and NF-κB activation. The use of AZM might provide possible benefits in periodontal therapy, with respect to both its antibacterial action and apparent anti-inflammatory effect.Journal of Periodontology 03/2011; 82(11):1623-31. · 2.60 Impact Factor -
Article: A model of spontaneous periodontitis in the miniature goat.
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ABSTRACT: The pathogenesis and progression of periodontal disease have been extensively studied through the use of animal models. However, no animal model has yet been established that is precisely similar to periodontitis in humans. In the present study, we examined the use of Shiba goats as a model for spontaneous periodontitis. Thirty-four Shiba goats (seven males and 27 females, aged 10 to 98 months) were used. We examined periodontitis in Shiba goats clinically, histopathologically, and microbiologically. The mean probing depth (PD) of the 68 teeth examined was 2.7 +/- 0.8 mm. The incidences of PD > or =3 and 4 mm were 46.4% and 22.1%, respectively. The incidence of bleeding on probing in 68 sites and in 34 animals was 60.7% and 73.5%, respectively. The formation of vertical alveolar bone defects and downgrowth of gingival epithelial cells were found in the areas of periodontitis. The prevalence of Tannerella forsythensis, Campylobacter rectus, Fusobacterium necrophorum, Fusobacterium nucleatum, and Actinobacillus actinomycetemcomitans in subgingival plaque by polymerase chain reaction was 46.4%, 28.5%, 28.5%, 17.8%, and 3.5%, respectively. These percentages were increased in subgingival plaque from PD > or =3 mm. The clinical, histopathological, and microbiological features of spontaneous periodontitis in Shiba goats were somewhat similar to those in human periodontitis. Moreover, there are some advantages of using the Shiba goat; the size of the oral cavity is suitable for periodontal treatment, and handling and housing are relatively easy. Therefore, these results suggest that the Shiba goat is a useful animal model for human periodontitis.Journal of Periodontology 05/2006; 77(5):847-55. · 2.60 Impact Factor -
Article: [The mechanism of bone resorption in chronic inflammation of periodontal disease].
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ABSTRACT: Periodontal disease is caused by infections with oral periodontitis-associated microorganisms. Virulence factors like lipopolysaccharide (LPS) from those microorganisms initiate host immune response and gingival chronic inflammation. As a result, elevated receptor activator of NF-kappaB ligand (RANKL) expression stimulates alveolar bone resorption followed by loss of teeth.Clinical calcium 03/2006; 16(2):241-47.
