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1.
Int J Mol Sci ; 24(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36834667

RESUMO

Candida albicans (Ca) is frequently detected in the peri-implant sulcus with peri-implantitis, a major postoperative complication after oral implant therapy. However, the involvement of Ca in the pathogenesis of peri-implantitis remains unclear. In this study, we aimed to clarify Ca prevalence in the peri-implant sulcus and investigated the effects of candidalysin (Clys), a toxin produced by Ca, on human gingival fibroblasts (HGFs). Peri-implant crevicular fluid (PICF) was cultured using CHROMagar and Ca colonization rate and colony numbers were calculated. The levels of interleukin (IL)-1ß and soluble IL-6 receptor (sIL-6R) in PICF were quantified by enzyme-linked immunosorbent assay (ELISA). Pro-inflammatory mediator production and intracellular signaling pathway (MAPK) activation in HGFs were measured by ELISA and Western blotting, respectively. The Ca colonization rate and the average number of colonies in the peri-implantitis group tended to be higher than those in the healthy group. IL-1ß and sIL-6R levels in the PICF were significantly higher in the peri-implantitis group than in the healthy group. Clys significantly induced IL-6 and pro-matrix metalloproteinase (MMP)-1 productions in HGFs, and co-stimulation with Clys and sIL-6R increased IL-6, pro-MMP-1, and IL-8 production levels in HGFs compared with Clys stimulation alone. These findings suggest that Clys from Ca plays a role in the pathogenesis of peri-implantitis by inducing pro-inflammatory mediators.


Assuntos
Implantes Dentários , Peri-Implantite , Humanos , Peri-Implantite/metabolismo , Candida albicans/metabolismo , Interleucina-6/farmacologia , Mediadores da Inflamação/farmacologia , Metaloproteinase 1 da Matriz/metabolismo , Fibroblastos/metabolismo , Líquido do Sulco Gengival/metabolismo
2.
J Periodontal Res ; 58(2): 262-273, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36579753

RESUMO

BACKGROUND AND OBJECTIVE: Lipocalin 2 (LCN2), a glycoprotein expressed in epithelial cells and leukocytes, has an antibacterial effect and plays a role in innate immunity. The delivery of LCN2 encapsulated in liposomes to oral epithelium may be useful to prevent oral infectious diseases. This study aimed to investigate the inhibitory effect of LCN2, artificially synthesized using a cell-free protein synthesis (CFPS) system, on the adhesion of Porphyromonas gingivalis to oral epithelial cells in order to approach oral healthcare using LCN2. METHODS: LCN 2 was synthesized using a CFPS system and assayed by Western blotting, mass spectrometry and enzyme-linked immunosorbent assay (ELISA). The bilayer liposomes were prepared by the spontaneous transfer method using 1,2-dioleoyl-sn-glycero-3 phosphocholine (DOPC), 3-sn-phosphatidylcholine from Egg Yolk (Egg-PC), and 1,2-dioleoyl-sn-glycero-3 phosphoethanolamine (DOPE). The cellular and medium fractions derived from the culture of oral epithelial cells with liposome-encapsulated LCN2 were assayed by Western blotting and ELISA. The effect of the synthesized LCN2 on adhesion of the labeled P. gingivalis to oral epithelial cells was investigated as an evaluation of its antibacterial activity. RESULTS: The synthesized LCN2 protein was identified by Western blotting; its amino acid sequence was similar to that of recombinant LCN2 protein. The additions of DOPE and octa-arginine in the outer lipid-layer components of liposome significantly increased the delivery of liposomes to epithelial cells. When oral epithelial cells were cultured with the synthesized and liposome-encapsulated LCN2, LCN2 was identified in the cellular and medium fractions by Western blotting and its concentration in the cellular fraction from the culture with the synthesized LCN2 was significantly higher than that of a template DNA-free protein. The synthesized LCN2 and liposome-encapsulated LCN2 significantly inhibited the adhesion of P. gingivalis to oral epithelial cells compared with template DNA-free protein. CONCLUSION: LCN2 was artificially synthesized by a CFPS system, encapsulated in liposomes, and delivered to oral epithelial cells, and demonstrated an antibacterial action against P. gingivalis. This approach may become a useful model for oral healthcare.


Assuntos
Lipossomos , Porphyromonas gingivalis , Humanos , Lipossomos/química , Lipocalina-2/farmacologia , Células Epiteliais
3.
Cells ; 11(21)2022 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-36359741

RESUMO

Periodontal diseases include periodontitis and gingival overgrowth. Periodontitis is a bacterial infectious disease, and its pathological cascade is regulated by many inflammatory cytokines secreted by immune or tissue cells, such as interleukin-6. In contrast, gingival overgrowth develops as a side effect of specific drugs, such as immunosuppressants, anticonvulsants, and calcium channel blockers. Human gingival fibroblasts (HGFs) are the most abundant cells in gingival connective tissue, and human periodontal ligament fibroblasts (HPLFs) are located between the teeth and alveolar bone. HGFs and HPLFs are both crucial for the remodeling and homeostasis of periodontal tissue, and their roles in the pathogenesis of periodontal diseases have been examined for 25 years. Various responses by HGFs or HPLFs contribute to the progression of periodontal diseases. This review summarizes the biological effects of HGFs and HPLFs on the pathogenesis of periodontal diseases.


Assuntos
Crescimento Excessivo da Gengiva , Periodontite , Humanos , Gengiva/patologia , Fibroblastos/patologia , Ligamento Periodontal , Periodontite/patologia , Crescimento Excessivo da Gengiva/patologia
4.
J Clin Med ; 10(3)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498415

RESUMO

Gan-Lu-Yin (GLY), a traditional Chinese herbal medicine, shows therapeutic effects on periodontitis, but that mechanism is not well known. This study aims to clarify the precise mechanism by investigating the inhibitory effects of GLY extracts on osteoclastogenesis in vitro and on bone resorption in periodontitis in vivo. RAW264.7 cells are cultured with soluble receptor activator of nuclear factor-kappa B (sRANKL) and GLY extracts (0.01-1.0 mg/mL), and stained for tartrate-resistant acid phosphatase (TRAP) to evaluate osteoclast differentiation. Experimental periodontitis is induced by placing a nylon ligature around the second maxillary molar in rats, and rats are administered GLY extracts (60 mg/kg) daily for 20 days. Their maxillae are collected on day 4 and 20, and the levels of alveolar bone resorption and osteoclast differentiation are estimated using micro-computed tomography (CT) and histological analysis, respectively. In RAW264.7 cells, GLY extracts significantly inhibit sRANKL-induced osteoclast differentiation at a concentration of more than 0.05 mg/mL. In experimental periodontitis, administering GLY extracts significantly decreases the number of TRAP-positive osteoclasts in the alveolar bone on day 4, and significantly inhibits the ligature-induced bone resorption on day 20. These results show that GLY extracts suppress bone resorption by inhibiting osteoclast differentiation in experimental periodontitis, suggesting that GLY extracts are potentially useful for oral care in periodontitis.

5.
J Periodontal Res ; 55(4): 539-550, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32170733

RESUMO

BACKGROUND AND OBJECTIVES: Diabetes mellitus (DM), a risk factor of periodontal diseases, exacerbates the pathological condition of periodontitis. A major factor for DM complications is advanced glycation end-products (AGEs) that accumulate in periodontal tissues and cause inflammatory events. Lipocalin 2 (LCN2) is an antimicrobial peptide and inflammation-related factor, and LCN2 levels increase in DM. In this study, the effects of AGEs and lipopolysaccharide of Porphyromonas gingivalis (P g-LPS) on LCN2 expression in human oral epithelial cells (TR146 cells) and the role of secreted LCN2 in periodontitis with DM were investigated. MATERIAL AND METHODS: TR146 cells were cultured with AGEs (AGE2) and control BSA and cell viability was estimated, or with P g-LPS. Conditioned medium and cell lysates were prepared from cultures of epithelial cells and used for Western blotting and ELISA to analyze LCN2, RAGE, IL-6, MAPK, and NF-κB. RNA was isolated from AGE-treated TR146 cells and differentiated HL-60 (D-HL-60) cells and used for quantitative real-time PCR to examine the expression of LCN2 and interleukin-6 (IL-6) mRNAs. RAGE- and LCN2-siRNAs (siRAGE, siLCN2) were transfected into epithelial cells, and AGE-induced LCN2 expression was investigated. D-HL-60 cells were co-cultured with TR146 cells that were transfected with siLCN2 and treated with AGEs, and IL-6 mRNA expression in D-HL-60 cells and cell migration was investigated. RESULTS: AGEs increased the expression levels of LCN2 and IL-6 in oral epithelial cells. siRAGE and a neutralizing antibody for RAGE inhibited AGE-induced LCN2 expression. AGEs stimulated the phosphorylation of ERK, p38, and NF-κB in epithelial cells, and their inhibitors suppressed AGE-induced LCN2 expression. In contrast, P g-LPS did not show a significant increase in LCN2 level in TR146 cells that expressed Toll-like receptor 2. In co-culture experiments, AGE-induced LCN2 inhibited IL-6 mRNA expression in D-HL-60 cells, and LCN2 knockdown in epithelial cells suppressed HL-60 cell migration. CONCLUSION: These results suggested that AGEs increase LCN2 expression via RAGE, MAPK, and NF-κB signaling pathways in oral epithelial cells, and secreted LCN2 may influence the pathological condition of periodontitis with DM.


Assuntos
Produtos Finais de Glicação Avançada , Lipocalina-2 , Porphyromonas gingivalis , Células Cultivadas , Células Epiteliais/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Lipocalina-2/genética , Lipocalina-2/metabolismo , NF-kappa B/metabolismo , Porphyromonas gingivalis/metabolismo , Receptor para Produtos Finais de Glicação Avançada/genética
6.
Biomed Res Int ; 2020: 7149408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149126

RESUMO

OBJECTIVE: Calprotectin is a heterocomplex of S100A8 and S100A9 and is mainly secreted from neutrophils, monocytes, and chondrocytes in inflammatory condition. Calprotectin binds to RAGE and TLR4 and induces the expression of proinflammatory chemokines and cytokines in various cells. Periodontitis is a chronic inflammatory disease that leads to gingival inflammation and alveolar bone resorption. Calprotectin levels in gingival crevicular fluid of periodontitis patients are higher than healthy patients. In the present study, the effects of S100A8 and S100A9 on the expressions of proinflammatory cytokines and bone metabolism-related factors in mouse osteocyte-like cells (MLO-Y4-A2) were investigated. DESIGN: MLO-Y4-A2 cells were treated with S100A8 and S100A9, and the expressions of RAGE, TLR4, RANKL, and several inflammatory cytokines were analyzed by PCR and Western blotting or ELISA methods. To investigate the intracellular signaling pathways, phosphorylation of MAPK and STAT3 was determined by Western blotting, and chemical specific inhibitors and siRNAs were used. RESULTS: Expressions of IL-6 and RANKL were increased by treatment with S100A9 but not S100A8. However, both S100A8 and S100A9 did not change expression of IL-1ß, IL-8, and TNF-α. Although RAGE and TLR4 expressions were not upregulated by S100A9 treatment, transfection of siRNA for RAGE and TLR4 significantly decreased IL-6 and RANKL expressions. In addition, S100A9 activated p38, ERK, and STAT3 signaling pathways, and inhibitors for these factors significantly decreased S100A9-induced IL-6 and RANKL expressions. CONCLUSIONS: These results indicated that S100A9 induces IL-6 and RANKL production via engagement with RAGE and TLR4 signalings in osteocytes and suggested that S100A9 may play important roles in the periodontal alveolar bone destruction.


Assuntos
Calgranulina B/metabolismo , Calgranulina B/farmacologia , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Fator de Transcrição STAT3/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Calgranulina A/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Camundongos , Fosforilação/efeitos dos fármacos , RNA Interferente Pequeno , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos
7.
Nutrients ; 12(1)2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31968635

RESUMO

Periodontitis is a polymicrobial infectious disease that leads to inflammation of the gingiva, resulting in teeth loss by various causes such as inflammation-mediated bone resorption. Recently, many investigators have reported that the periodontitis resulting from persistent low-grade infection of Gram-negative bacteria such as Porphyromonas gingivalis (Pg) is associated with increased atherosclerosis, diabetes mellitus, and other systemic diseases through blood stream. On the other hand, carotenoids belong among phytochemicals that are responsible for different colors of the foods. It is important to examine whether carotenoids are effective to the inhibition of periodontal infection/inflammation cascades. This review summarizes the advanced state of knowledge about suppression of periodontal infection by several carotenoids. A series of findings suggest that carotenoids intake may provide novel strategy for periodontitis treatment, although further study will be needed.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Infecções por Bacteroidaceae/tratamento farmacológico , Carotenoides/uso terapêutico , Periodontite/tratamento farmacológico , Porphyromonas gingivalis/patogenicidade , Animais , Anti-Inflamatórios/efeitos adversos , Antioxidantes/efeitos adversos , Infecções por Bacteroidaceae/microbiologia , Carotenoides/efeitos adversos , Humanos , Mediadores da Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Periodontite/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Resultado do Tratamento
8.
Clin Oral Investig ; 24(2): 833-840, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31197658

RESUMO

OBJECTIVES: Infective endocarditis (IE) is a life-threatening infectious disease, but the pathogenesis of the disease remains uncertain. The objective of this study was to examine whether oral infectious conditions are associated with the occurrence of IE in valvular heart disease (VHD) patients. MATERIALS AND METHODS: A total of 119 periodontitis (P) patients with or without VHD were enrolled, and cross-sectional analyses were performed. Patients were classified as follows: (1) mild-to-moderate P without VHD, (2) mild-to-moderate P with VHD, (3) severe P without VHD, or (4) severe P with VHD. A total of 78 VHD patients were classified as (1) VHD without IE or (2) VHD with IE. Conditional logistic regression analysis was performed to compute the odds ratio (OR) and 95% confidence interval (CI). RESULTS: No significant differences were observed between patients with or without VHD in oral conditions. A significant increase in the percentage of alveolar bone loss in VHD patients with IE was observed compared with that of patients without IE. The ratio of both Porphyromonas gingivalis (Pg) IgG titer > 1.68 and Pg fimA type II genotype in patients with IE was significantly higher than in patients without IE. There was a significant correlation between the occurrence of IE and clinical oral findings (number of remaining teeth: OR, 0.17; rate of alveolar bone loss > 40%: OR, 11.8). CONCLUSIONS: VHD patients with IE might have severe periodontitis compared with patients without IE, although further investigation will be needed because this is based on only 7 VHD patients with IE. CLINICAL RELEVANCE: The patients with IE had fewer remaining teeth, more advanced bone resorption compared with those of patients without IE. These findings suggest a possible association between the occurrence of IE and periodontal infection.


Assuntos
Endocardite , Doenças das Valvas Cardíacas , Periodontite , Estudos Transversais , Endocardite/epidemiologia , Endocardite/etiologia , Doenças das Valvas Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/etiologia , Humanos , Incidência , Periodontite/complicações
9.
Molecules ; 24(20)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31619000

RESUMO

Advanced glycation end-products (AGEs) cause diabetes mellitus (DM) complications and accumulate more highly in periodontal tissues of patients with periodontitis and DM. AGEs aggravate periodontitis with DM by increasing the expression of inflammation-related factors in periodontal tissues. 6-Shogaol, a major compound in ginger, has anti-inflammatory and anti-oxidative activities. However, the influence of shogaol on DM-associated periodontitis is not well known. In this study, the effects of 6-shogaol on AGEs-induced oxidative and anti-oxidative responses, and IL-6 and ICAM-1 expression in human gingival fibroblasts (HGFs) were investigated. When HGFs were cultured with 6-shogaol and AGEs, the activities of reactive oxygen species (ROS) and antioxidant enzymes (heme oxygenase-1 [HO-1] and NAD(P)H quinone dehydrogenase 1 [NQO1]), and IL-6 and ICAM-1 expressions were investigated. RAGE expression and phosphorylation of MAPKs and NF-κB were examined by western blotting. 6-Shogaol significantly inhibited AGEs-induced ROS activity, and increased HO-1 and NQO1 levels compared with the AGEs-treated cells. The AGEs-stimulated expression levels of receptor of AGE (RAGE), IL-6 and ICAM-1 and the phosphorylation of p38, ERK and p65 were attenuated by 6-shogaol. These results suggested that 6-shogaol inhibits AGEs-induced inflammatory responses by regulating oxidative and anti-oxidative activities and may have protective effects on periodontitis with DM.


Assuntos
Catecóis/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Produtos Finais de Glicação Avançada/genética , Molécula 1 de Adesão Intercelular/genética , Interleucina-6/genética , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Gengiva/citologia , Produtos Finais de Glicação Avançada/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Bone ; 122: 22-30, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30735798

RESUMO

Sclerostin is a secreted glycoprotein that is mainly expressed in osteocytes, exerts negative effects on bone formation, and is present at elevated levels in diabetes mellitus (DM). Periodontitis is an infectious disease caused by periodontopathic bacteria, a complication of DM, and sometimes associated with severe inflammation and alveolar bone resorption. Advanced glycation end-products (AGEs) are a major pathogen in DM complications and adversely influence periodontitis in DM patients. In the present study, the effects of AGE2 and Porphyromonas gingivalis lipopolysaccharide (P-LPS) on the expression of sclerostin in mouse osteocyte-like cells (MLO-Y4-A2 cells) and its function in osteoblast differentiation were investigated. AGE2 and P-LPS up-regulated the expressions of receptor of AGE (RAGE) and Toll-like receptor 2 (TLR2), respectively, and significantly up-regulated that of sclerostin and interleukin 6 (IL-6) in osteocytes. Sclerostin, RAGE and TLR2 levels were synergistically increased by AGE2 and P-LPS. The siRNAs of RAGE and TLR2 significantly inhibited AGE2- and P-LPS-induced sclerostin expression. AGE2 up-regulated sclerostin expression in osteocyte-like cells via the RAGE, ERK and JNK, and NF-κB signal pathways. On the other hand, P-LPS elevated sclerostin levels via the TLR2, JNK and p38, and NF-κB signal pathways. When osteocytes pre-treated with AGE2 and P-LPS and osteoblastic cells (MC3T3-E1) were co-cultured in the medium with a sclerostin-neutralizing antibody, AGE2- and P-LPS-induced decreases in alkaline phosphatase activity and Runx2 expression in osteoblastic cells were significantly inhibited by the sclerostin-neutralizing antibody. These results suggest that AGE2 and P-LPS influence bone metabolism and inflammation through the regulation of sclerostin expression, and may aggravate periodontitis with DM.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Lipopolissacarídeos/farmacologia , Osteócitos/metabolismo , Porphyromonas gingivalis/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Interleucina-6/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteócitos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Receptor 2 Toll-Like/metabolismo
11.
Cell Physiol Biochem ; 50(3): 973-986, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30355945

RESUMO

BACKGROUND/AIMS: Diabetic patients are susceptible to severe periodontitis, but the precise mechanism is not fully understood. Aim of this study was to explore the biological pathogenesis of severe periodontitis in diabetic patients focusing on the crosstalk of human gingival fibroblasts (HGFs) and macrophages. METHODS: A total of 70 periodontitis patients with or without diabetes mellitus (DM) were enrolled, and the statistical relationships of diabetic conditions to the periodontal inflammatory parameters were examined by cross-sectional study. In in vitro study, HGFs cell line CRL-2014® (ATCC) and differentiated THP-1 macrophages were cultured with normal glucose (NG: 5.5 mM) or high glucose (HG: 25 mM) condition, and treated with indicated inflammatory factors such as calprotectin (CPT), interleukin (IL)-1ß and IL-6. To examine the effects of HG on soluble IL-6 receptor (sIL-6R) production in THP-1 macrophages, the supernatants were collected and the sIL-6R levels were measured by ELISA. To examine the effects of HG on IL-1ß or IL-6-induced matrix metalloproteinase (MMPs) production in HGFs, the supernatants were collected. Levels of MMP-1 and tissue inhibitor of MMP-1 (TIMP-1) were measured by ELISA. Finally, after conditioned medium (CM) from THP-1 macrophages cultured with NG or HG conditions was collected, HGFs were treated with the CM. The supernatants were collected 24 hours later and the levels of MMP-1 and TIMP-1 were measured. To examine the specific effects of IL-1ß contained in CM on MMP-1 and TIMP-1 production in HGFs, IL-1 receptor antagonist (IL-1ra) was used. RESULTS: There were statistical correlation between IL-1ß and sIL-6R levels in gingival crevicular fluid (GCF) and HbA1c in periodontitis patients with DM (IL-1ß: P=0.035, sIL-6R: P=0.040). HG and CPT significantly induced sIL-6R production in THP-1 macrophages. HG significantly enhanced IL-1ß or IL-6/sIL-6R-induced MMP-1 production in HGFs. The increase of MMP-1 by both IL-1ß and IL-6/sIL-6R was significantly inhibited by specific ERK or IκB inhibitors. Corresponding to the regulation of MMP-1 production, HG condition increased the phosphorylation of p44/42 MAPK and IκBα in HGFs treated with IL-1ß or IL-6/sIL-6R. Finally, MMP-1 production in HGFs cultured with HG increased significantly by CM from THP-1 macrophages cultured with HG. The induction of MMP-1 by the CM from THP-1 macrophages cultured with HG was significantly inhibited by dose dependent of IL-1ra in HGFs cultured with HG. CONCLUSION: Diabetic conditions such as HG induce IL-1ß and sIL-6R production from macrophages in inflammatory periodontal tissues and may exacerbate the periodontitis synergistically via MMP-1 production from HGFs.


Assuntos
Complicações do Diabetes/patologia , Glucose/farmacologia , Interleucina-1beta/metabolismo , Periodontite/patologia , Regulação para Cima/efeitos dos fármacos , Idoso , Estudos Transversais , Feminino , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Gengiva/citologia , Hemoglobinas Glicadas/metabolismo , Humanos , Complexo Antígeno L1 Leucocitário/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Metaloproteinase 1 da Matriz/metabolismo , Pessoa de Meia-Idade , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Periodontite/complicações , Receptores de Interleucina-6/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo
12.
Exp Gerontol ; 110: 86-91, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29842897

RESUMO

BACKGROUND: There is limited information on the relationship of low body mass index (BMI) to the geriatric conditions in elderly patients. OBJECTIVE: The objective of this study is to investigate whether low BMI associates with geriatric status in elderly patients by calculating suitable cut-off point of BMI for assessment of geriatric conditions. METHOD: A total of 1223 elderly patients was enrolled (male/female: N = 472/751), and cut-off point of the BMI values to assess the geriatric status such as aspiration pneumonia, cognitive impairment was determined by receiver operating characteristic (ROC) analyses. Logistic regression analyses were performed to examine the association between several geriatric status and low BMI. Of these patients, 262 patients (male/female: 101/161) had received standard rehabilitation treatment. Functional Independence Measure (FIM) scores were measured both at admission and discharge to calculate FIM gain and efficiency, and retrospective cohort study was performed. RESULTS: Cut-off point of BMI value to assess the geriatric status was determined (19.0 kg/m2). Significant associations of low BMI to several geriatric factors such as loss of posterior occlusion, cognitive impairment were observed in both male and female. FIM scores in above cut-off point group were significantly higher than in below cut-off point group in female (FIM gain, P = 0.0005; FIM efficiency, P = 0.0025, Mann-Whitney U test). On the other hand, there were no significant differences between low and above BMI cut-off point in FIM scores of male patients. CONCLUSION: Low BMI might be a useful parameter to evaluate the geriatric status, and the viewpoint would contribute to decide the care plan for the good end-of-life of elderly.


Assuntos
Atividades Cotidianas , Índice de Massa Corporal , Avaliação Geriátrica/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Estado Nutricional , Curva ROC , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores Sexuais
13.
J Cell Physiol ; 233(9): 6393-6400, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29574949

RESUMO

Periodontitis is a bacterial infectious disease, and many inflammatory cytokines regulate periodontitis pathophysiology through a crosstalk between tissue cells and immune cells. Interleukin (IL)-6 is an important cytokine involved in the regulation of host response to bacterial infection. Human Gingival Fibroblasts (HGFs) are the most abundant cells in gingival connective tissues. Various HGF responses to periodontal pathogens or inflammatory cytokines contribute to the development of periodontitis. Lipopolysaccharide derived from Porphyromonas gingivalis (Pg LPS) and IL-1ß significantly increase IL-6 production in HGFs. However, IL-6 cannot function in HGFs without the soluble form of the IL-6 receptor (sIL-6R), because HGFs do not express sufficient cell surface IL-6R to bind appreciable levels of IL-6. Importantly, sIL-6R is essential for IL-6 signaling in HGFs, and the sIL-6R is produced by differentiated THP-1 cells treated with IL-6. Calprotectin, a heterodimer of S100A8 and S100A9, is released during inflammation and significantly induces IL-6 production in HGFs via toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signals. Calprotectin also induces sIL-6R production in differentiated THP-1 cells. IL-6 induces vascular endothelial growth factor (VEGF), matrix-metalloproteinase-1 (MMP-1), and cathepsin L production in HGFs in the presence of sIL-6R. Taken together, calprotectin-induced IL-6 production in HGFs may cause periodontitis progression through a crosstalk of fibroblasts and macrophages. There are many reports that examine how cytokines are released from HGFs to cause beneficial or harmful effects in inflamed periodontal lesions. This review explores the pathophysiology of periodontitis by focusing IL-6-mediated crosstalk of HGFs and macrophages.


Assuntos
Citocinas/metabolismo , Fibroblastos/metabolismo , Gengiva/metabolismo , Interleucina-6/metabolismo , Periodontite/metabolismo , Humanos , Inflamação/metabolismo , Transdução de Sinais/fisiologia
14.
New Microbiol ; 41(1): 52-60, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29505064

RESUMO

An insertion sequence, IS1598 (IsPg4) has been found in virulent strains of Porphyromonas gingivalis in a murine abscess model. The present study was performed to investigate the effects of genetic rearrangements by IS1598 on the phenotypic characteristics of the virulent strains. For this purpose, we searched for a common insertion site of IS1598 among the virulent strains. Through cloning and database search, a common insertion site was identified beside an nrdD-like gene in the virulent FDC 381, W83 and W50 strains. In this region, predicted promoters of the nrdD-like gene and IS1598 are located in tandem, and accumulation of nrdD-like gene mRNA was 5-fold higher in virulent strains (W83, W50, FDC 381) than avirulent strains (ATCC33277, SU63, SUNY1021, ESO59 without IS1598). The role of the nrdD-like gene in virulence of P. gingivalis was investigated by constructing a nrdD-deficient mutant. In the murine abscess model, the parental W83 strain produced necrotic abscesses, while the nrdD-deficient mutant had almost lost this ability. Insertion of IS1598 into the nrdD-like gene promoter region may be related to the phenotypic differences in virulence among P. gingivalis strains through upregulation of the expression of this gene.


Assuntos
Proteínas de Bactérias/metabolismo , Porphyromonas gingivalis/classificação , Porphyromonas gingivalis/patogenicidade , Ribonucleotídeo Redutases/metabolismo , Regulação para Cima/fisiologia , Abscesso/microbiologia , Proteínas de Bactérias/genética , Regulação Enzimológica da Expressão Gênica , Genes Bacterianos , Genoma Bacteriano , Humanos , Mutagênese Insercional , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ribonucleotídeo Redutases/genética , Virulência
15.
Clin Oral Investig ; 22(7): 2575-2580, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29388021

RESUMO

OBJECTIVES: The objective of this study was to investigate the relationship of the incidence of aspiration pneumonia to cognitive impairment and the oral condition. MATERIALS AND METHODS: A total of 1174 elderly patients were analyzed in a cross-sectional study. Cognitive function was evaluated by the Clinical Dementia Rating scale and the oral condition was evaluated by inspection and palpation. Swallowing was examined in 196 patients by video-endoscopic evaluation. The Mann-Whitney U test or chi-square test was used for statistical analysis. Conditional logistic regression analysis was performed to compute the odds ratio (OR) and 95% confidence interval (CI). RESULTS: Loss of posterior occlusion, impaired tongue movements, and impaired cognition were factors significantly related to aspiration pneumonia. The incidence of aspiration pneumonia was higher in patients with both cognitive impairment and loss of posterior occlusion compared with those having either factor alone (OR: 5.16). There was no statistical association between impaired swallowing and the incidence of aspiration pneumonia in elderly patients with normal cognitive function (cognitive impairment, OR: 3.45; normal function, OR: 0.94). CONCLUSION: Co-existence of cognitive impairment and oral frailty significantly enhances the risk of aspiration pneumonia. CLINICAL RELEVANCE: Early and simple evaluation of the oral condition and cognitive function can predict the risk of aspiration pneumonia.


Assuntos
Disfunção Cognitiva/epidemiologia , Saúde Bucal , Pneumonia Aspirativa/epidemiologia , Idoso de 80 Anos ou mais , Disfunção Cognitiva/etiologia , Estudos Transversais , Endoscopia , Feminino , Idoso Fragilizado , Humanos , Masculino , Pneumonia Aspirativa/etiologia , Fatores de Risco , Gravação em Vídeo
16.
J Periodontol ; 89(1): 67-75, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28875823

RESUMO

BACKGROUND: Calprotectin, an inflammation-related protein, is present in gingival crevicular fluid (GCF), and the determination of calprotectin is useful for diagnosing periodontal diseases. The authors have recently developed a novel immunochromatographic (IC) chip system to determine calprotectin levels in GCF. In the present study, the usefulness of this diagnostic system is investigated in patients with periodontal diseases. METHODS: Thirty-six patients with periodontal diseases participated in this clinical test at multiple centers. Periodontitis sites (n = 118) and non-periodontitis (healthy) sites (n = 120) were selected after periodontal examination. GCF collection and periodontal examination were performed at baseline, after supragingival and subgingival scaling and root planing. Calprotectin levels in GCF were determined using a novel IC chip system and evaluated as a visual score and an IC reader value. Correlations between GCF calprotectin levels, clinical indicators, and changes in calprotectin levels by periodontal treatments were investigated. Receiver operating characteristic (ROC) analysis of IC reader value for GCF calprotectin was performed to predict periodontal diseases. RESULTS: The visual score of GCF calprotectin was highly correlated with the IC reader value. IC reader values of GCF calprotectin in the periodontitis group were higher than those of the healthy group at three dental examination stages, and they significantly decreased with periodontal treatments. Visual scores and IC reader values of GCF calprotectin were correlated to levels of clinical indicators. ROC analysis for GCF calprotectin showed an optimal cutoff value to predict periodontal diseases. CONCLUSION: Determination of GCF calprotectin using a novel IC chip system is useful for diagnosis of periodontal diseases.


Assuntos
Líquido do Sulco Gengival , Doenças Periodontais , Biomarcadores , Raspagem Dentária , Humanos , Imunoensaio , Complexo Antígeno L1 Leucocitário , Índice Periodontal
17.
Cell Biol Int ; 42(1): 105-111, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28906038

RESUMO

Periodontitis is associated with development of diabetes mellitus. Although lipopolysaccharide (LPS) of Porphyromonas gingivalis (Pg), a major pathogen of periodontitis, may lead the progression of diabetes complications, the precise mechanisms are unclear. We, therefore, investigated the effects of ß-carotene on production of Pg LPS-induced inflammatory cytokines in human monocytes cultured high glucose (HG) condition. THP-1 cells were cultured under 5.5 mM or 25 mM glucose conditions, and cells were stimulated with Pg LPS. To investigate the productivity of TNF-α, IL-6, and MCP-1, cell supernatants were collected for ELISA. To examine the effects of NF-kB signals on cytokine production, Bay11-7082 was used. HG enhanced Pg LPS-induced production of TNF-α, IL-6, and MCP-1 via NF-kB signals in THP-1. ß-carotene suppressed the enhancement of the Pg LPS-induced cytokine production in THP-1 via NF-κB inactivation. Our results suggest that ß-carotene might be a potential anti-inflammatory nutrient for circulating Pg LPS-mediated cytokine production in diabetic patients with periodontitis.


Assuntos
Glucose/farmacologia , beta Caroteno/metabolismo , beta Caroteno/farmacologia , Técnicas de Cultura de Células/métodos , Citocinas/metabolismo , Citocinas/farmacologia , Complicações do Diabetes/fisiopatologia , Glucose/metabolismo , Humanos , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Monócitos/efeitos dos fármacos , NF-kappa B/metabolismo , NF-kappa B/farmacologia , Periodontite/metabolismo , Porphyromonas gingivalis/efeitos dos fármacos , Células THP-1/metabolismo , Células THP-1/fisiologia , beta Caroteno/fisiologia
18.
J Cell Biochem ; 119(2): 1591-1603, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28771806

RESUMO

Accumulation of advanced glycation end-products (AGEs) in periodontal tissues of patients with diabetes mellitus aggravates periodontitis, but the mechanisms are unknown. Calprotectin, a heterocomplex of S100A8 and S100A9 proteins, is a constitutive cytoplasmic component of healthy gingival epithelial cells. This study aimed at investigating the effects of AGE and Porphyromonas gingivalis lipopolysaccharide (PgLPS) on calprotectin expression in the human gingival epithelial cell line OBA-9. AGE and PgLPS increased the expression of S100A8 and S100A9 mRNAs, and AGE+PgLPS co-stimulation amplified their expression in OBA-9 cells. A higher concentration of calprotectin in cell lysates was also induced by stimulation with AGE and/or PgLPS. S100A8 was mainly translocated from the nucleus to the cytoplasm by AGE stimulation, while cytoplasmic localization of S100A9 was not altered following stimulation with AGE and/or PgLPS. Calprotectin was found in the cytoplasm of BSA-treated cells, but cytoplasmic and nuclear localization was observed following stimulation with AGE and/or PgLPS. AGE-induced S100A8, and S100A9 mRNA expression was partially suppressed by RAGE-specific siRNA. In contrast, PgLPS-induced S100A8 and S100A9 mRNA expression was strongly suppressed by TLR2-specific siRNA. Furthermore, the inhibition of p38, JNK MAPK, and NF-κB attenuated AGE- and PgLPS-induced S100A8 and S100A9 mRNA expression. Taken together, these results demonstrate that AGE acts in synergy with PgLPS to stimulate RAGE and TLR2 expression and activate p38, JNK MAPK, and NF-κB signaling pathways, resulting in increased activation of calprotectin (S100A8/S100A9) in human gingival epithelial cells. Our results suggest that calprotectin may be involved in the pathogenesis of diabetic periodontitis.


Assuntos
Calgranulina A/genética , Calgranulina B/genética , Gengiva/metabolismo , Produtos Finais de Glicação Avançada/efeitos adversos , Lipopolissacarídeos/efeitos adversos , Porphyromonas gingivalis/metabolismo , Calgranulina A/metabolismo , Calgranulina B/metabolismo , Linhagem Celular , Núcleo Celular/genética , Núcleo Celular/metabolismo , Citoplasma/genética , Citoplasma/metabolismo , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Gengiva/citologia , Gengiva/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases , Periodontite/genética , Periodontite/metabolismo , Regulação para Cima
19.
Biomed Pharmacother ; 97: 765-770, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29107933

RESUMO

Calcitonin (CTN), a calcium regulatory hormone, promotes calcium diuresis from the kidney and suppresses bone resorption. The objective of this study was to evaluate whether the topical and intermittent application of CTN inhibits alveolar bone resorption using ligature-induced experimental periodontitis in rats. Experimental periodontitis was induced by placing a nylon ligature around maxillary molars of 8-week-old male Wistar rats for 20 days. Thirty-two rats were divided into four groups: basal sham control group, periodontitis group, periodontitis plus 0.2 U CTN (low dose), and periodontitis plus 1.0 U CTN (high dose) group. To investigate the effects of CTN on alveolar bone resorption, CTN was topically injected into the palatal gingivae every 2 days after ligature removal (day 0). Micro-computed tomography (CT) analysis was performed for linear parameter assessment of alveolar bone on day 5 and day 14. Periodontal tissues were examined histo-pathologically to assess the differences among the study groups. Micro-CT images showed that alveolar bone resorption was induced statistically around the molar of ligatured rats on day 5 and day 14. The amount of bone resorption was more severe on day 14 than that on day 5. On day 5, only high-dose CTN treatment significantly suppressed bone resorption. In addition, both doses of CTN significantly suppressed bone resorption on day 14. Histological examination clarified that there were fewer TRAP-positive cells in the CTN treatment groups than in the periodontitis group on day 5. Local administration of CTN decreased alveolar bone resorption by regulating osteoclast activation in rats with periodontitis.


Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Conservadores da Densidade Óssea/administração & dosagem , Calcitonina/administração & dosagem , Periodontite/tratamento farmacológico , Administração Tópica , Perda do Osso Alveolar/patologia , Animais , Conservadores da Densidade Óssea/farmacologia , Calcitonina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Periodontite/patologia , Ratos , Ratos Wistar , Índice de Gravidade de Doença , Fatores de Tempo , Microtomografia por Raio-X
20.
Aging Clin Exp Res ; 30(1): 77-80, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28391586

RESUMO

BACKGROUND: In end-of-life care of elderly, the decision of care plan including gastrostomy is difficult frequently because of insufficient knowledge relating the life prognosis of elderly. It is important the families to decide correctly the life prognosis of elderly with geriatric diseases. Our purpose is to examine the significant factors for predicting life prognosis of elderly in end-of-life care. METHODS: A total of 320 elderly patients was enrolled (male/female 151/169; averaged age: male 84.7 ± 5.9 year, female 86.8 ± 6.3 year) and retrospective analyses were performed. The elderly patients were classified as either: (1) with or without past illness of aspiration pneumonia; (2) with or without incidence of cerebrovascular disorder; (3) impaired or normal cognitive function; (4) impaired or normal swallowing function, and performed Kaplan-Meier survival analysis. Swallowing function was examined using video endoscopic (VE) evaluation method. The Kaplan-Meier analysis of the number of days from implementation of VE test (day 0) to death was evaluated with the log-rank Mantel-Cox test. The maximum follow-up time recorded was 180 days. RESULTS: There were no significant differences in number of days when divided with or without past illness of aspiration pneumonia, cerebrovascular disorder and impaired cognitive function. The survival probabilities of elderly with impaired swallowing function were significant lower than in elderly with the normal function. CONCLUSIONS: For judgement of life prognosis, the condition of being frail such as impaired swallowing function might be a useful factor, and the viewpoint would contribute to decide the treatment plan for the good end-of-life care of elderly.


Assuntos
Transtornos de Deglutição/mortalidade , Deglutição/fisiologia , Assistência Terminal/métodos , Idoso , Idoso de 80 Anos ou mais , Transtornos Cerebrovasculares/epidemiologia , Disfunção Cognitiva/epidemiologia , Transtornos de Deglutição/terapia , Feminino , Fragilidade/epidemiologia , Gastrostomia , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pneumonia Aspirativa/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida
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