A Controversial Role for IL-12 in Immune Response and Bone Resorption at Apical Periodontal Sites

Periapical lesions are inflammatory conditions of tooth periapical tissues, triggered by dental pulp infection and characterized by exudation of immune cells to the affected tissues and production of inflammatory mediators such as cytokines. The inflammatory periapical reaction is mainly driven by Th1, Th2, and Th17 responses, and such polarization may modulate progression of the disease and expression of bone proresorptive cytokines. IL-12 is a potent inducer of IFN-γ production, which stimulates Th1 effector cells. Many evidences have shown a positive correlation between the bone resorptive cytokine IL-1β and the production of IL-12 and IFN-γ. Furthermore, IL-12 may have a potential role in the release of bone resorptive mediators and blockade of Th2 cytokines, affecting the progression of periapical bone loss. Nevertheless, IL-12 and IFN-γ have also been described as suppressors of osteoclast differentiation and activation, favoring bone maintenance. This paper focuses on the controversial roles of IL-12 in periapical lesions

Dysbiotic oral microbiota contributes to alveolar bone loss associated with obesity in mice

Periodontal diseases (PD) are inflammatory conditions that affect the teeth supporting tissues. Increased body fat tissues may contribute to activation of the systemic inflammatory response, leading to comorbidities. Some studies have shown that individuals with obesity present higher incidence of PD than eutrophics. Objective: To investigate the impact of obesity on periodontal tissues and oral microbiota in mice. Methodology: Two obesity mice models were performed, one using 12 weeks of the dietary protocol with a high-fat (HF) diet in C57BL/6 mice and the other using leptin receptor-deficient mice (db/db-/-), which became spontaneously obese. After euthanasia, a DNA-DNA hybridization technique was employed to evaluate the microbiota composition and topical application of chlorhexidine (CHX), an antiseptic, was used to investigate the impact of the oral microbiota on the alveolar bone regarding obesity. Results: Increased adipose tissue may induce alveolar bone loss, neutrophil recruitment, and changes in the oral biofilm, similar to that observed in an experimental model of PD. Topical application of CHX impaired bone changes. Conclusion: Obesity may induce changes in the oral microbiota and neutrophil recruitment, which are associated with alveolar bone loss

Papel de mediadores inflamatórios na doença periodontal induzida por Aggregatibacter actinomycetemcomitans em camundongos

Exportado OPUSMade available in DSpace on 2019-08-14T05:59:57Z (GMT). No. of bitstreams: 1 capapdf.pdf: 95052 bytes, checksum: b9a9c97c22973498f1db1f8688685756 (MD5) Previous issue date: 12As doenças periodontais (DP) são doenças inflamatórias provocadas por microorganismos periodontopatogênicos como Aggregatibacteractinomycetemcomitans (Aa), que podem causar destruição dos tecidosperiodontais. A inoculação oral de camundongos com Aa ou a injeção de LPS de Aa (AaLPS) induz à perda óssea alveolar acentuada e à produção local de mediadores inflamatórios à semelhança da forma agressiva da DP em seres humanos. Entretanto, a sinalização de AaLPS, o papel de alguns mediadores como IL-12, MIF e mediadores lipídicos, tais como PAF e leucotrienos na reabsorção óssea alveolar durante as DP não são bem conhecidos. No presente estudo, reabsorção óssea alveolar foi induzida por injeções de AaLPS. Ainoculação oral de Aa foi utilizada para indução de DP experimental emcamundongos selvagens (WT) ou deficientes na produção de MIF (MIF-/-), no receptor de PAF (PAFR-/-) ou na produção de 5-LO (5-LO-/-) pela. Nossos resultados mostram que a sinalização de AaLPS ocorre de maneira dependente de MyD88, culminando na perda óssea alveolar, provavelmente pela produção de TNF-. Foi observado um infiltrado neutrofílico acompanhado de produção de mediadores inflamatórios e perda óssea alveolar após inoculação de Aa em camundongos selvagens, entretanto, na ausência de MIF, PAFR e 5-LO, oscamundongos apresentaram reduzida perda de osso alveolar, quando comparado aos camundongos WT. Em camundongos MIF-/- e 5-LO-/- esse fenótipo foi associado à diminuição do acúmulo de neutrófilos. Camundongos WT, bem como PAFR-/- submetidos à inoculação oral de Aa apresentaram acúmulo de neutrófilos e aumento dos níveis de CXCL-1 e TNF- nos tecidos periodontais ao longo do período experimental. In vitro, AaLPS induziu maior atividade osteoclástica, a qualfoi dependente de MIF. O bloqueio do PAF e da produção de 5-LO impediu a atividade de reabsorção de osteoclastos ativados por AaLPS. Em conclusão, MIF e 5-LO têm papel no controle da resposta inflamatória periodontal, contribuíndo significativamente para a progressão da perda óssea alveolar e afetando diretamente a diferenciação e a atividade dos osteoclastos, enquanto PAF afetadiretamente a ativação de osteoclastos, sem interferências na respostainflamatória.Periodontal disease (PD) is a chronic inflammatory and alveolar bone destructive disease triggered by microorganisms as Aggregatibacter actinomycetemcomitans (Aa). Oral inoculation of mice with Aa or injections of its LPS (AaLPS) induce marked alveolar bone loss and local production of inflammatory mediators as clinical aggressive forms of PD in humans. Perhaps, signaling involved in recognition of AaLPS and the role of some mediators such as IL-12, MIF, lipidic mediators such as PAF and leukotrienes in alveolar bone resorption during PD is not well known. In the present study, experimental alveolar bone loss was inducedby AaLPS injections in wild-type (WT) mice and experimental PD was induced in WT or MIF (MIF-/-), PAFR (PAFR-/-) or 5-LO (5-LO-/-) knockout mice through oral inoculation of Aa. Our results show that the signaling through MyD88 is important to alveolar bone loss induced by AaLPS likely by activation of TNF- production. Oral inoculation of Aa induced significant neutrophil influx, production of inflammatory mediators and alveolar bone loss in WT mice. Perhaps, in the absence of MIF, PAFR or 5-LO, mice had reduced alveolar bone loss when compared to WT mice. In MIF-/- and 5-LO-/- mice this phenotype was associated with decreased neutrophil accumulation. WT mice as well as PAFR-/- mice submitted to oral inoculation of Aa presented neutrophil accumulation, increasedlevels of CXCL-1 and TNF- in periodontal tissues. In vitro, AaLPS enhanced osteoclastic activity in a MIF-dependent manner and the blockage of PAF and 5-LO impaired the resorption activity of AaLPS-activated osteoclasts. In conclusion, MIF and 5-LO has role in controlling bacterial growth in the context of PD contributing significantly to the progression of bone loss during PD by directly affecting differentiation and activity of osteoclasts and PAF directly affects osteoclasts activation without interferences in inflammatory response

Brain-Derived Neurotrophic Factor in Chronic Periodontitis

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor family. Outside the nervous system, BDNF has been shown to be expressed in various nonneural tissues, such as periodontal ligament, dental pulp, and odontoblasts. Although a role for BDNF in periodontal regeneration has been suggested, a function for BDNF in periodontal disease has not yet been studied. The aim of this study was to analyze the BDNF levels in periodontal tissues of patients with chronic periodontitis (CP) and periodontally healthy controls (HC). All subjects were genotyped for the rs4923463 and rs6265 BDNF polymorphisms. Periodontal tissues were collected for ELISA, myeloperoxidase (MPO), and microscopic analysis from 28 CP patients and 29 HC subjects. BDNF levels were increased in CP patients compared to HC subjects. A negative correlation was observed when analyzing concentration of BDNF and IL-10 in inflamed periodontium. No differences in frequencies of BDNF genotypes between CP and HC subjects were observed. However, BDNF genotype GG was associated with increased levels of BDNF, TNF-α, and CXCL10 in CP patients. In conclusion, BDNF seems to be associated with periodontal disease process, but the specific role of BDNF still needs to be clarified

Association between Polymorphisms in Interleukin-17A and -17F Genes and Chronic Periodontal Disease

Objective. Interleukin-17 (IL-17) is a cytokine that induces neutrophil recruitment and the release of inflammatory mediators in several inflammatory conditions; nevertheless, the involvement of IL-17 gene polymorphisms in chronic periodontitis (CP) has not been addressed yet. Our aim was to evaluate the association between periodontal status and the polymorphisms IL-17A G197A and IL-17F C7488T in subjects with CP along with their impact on levels of inflammatory mediators. Material and Methods. Genomic DNA was obtained from 30 CP patients and 30 healthy controls (HCs). IL-17A G197A and IL-17F C7488T polymorphisms were determined using PCR-RFLP. Serum and periodontal tissues were collected and processed for ELISA, myeloperoxidase (MPO), and/or microscopic analysis. Results. The frequencies of genotypes in the CP group were significantly different from those of HC. Odds ratio indicated that increased risks for CP were associated with the -197A allele, not with the -7488T allele. In addition, the -197A allele was correlated with worse clinical parameters, higher MPO activity, and increased expression of inflammatory mediators (IL-17A and IL-8) than the other genotypes. Conclusions. These results indicate that the IL-17A -197A allele is associated with increased risk for CP, likely because this genotype relates to the enhanced inflammation in periodontal tissues