RESUMO
AIM: Apical periodontitis is an inflammatory disorder triggered by an immune response to bacterial infection, leading to the periapical tissue damage and alveolar resorption. However, the underlying mechanisms driving this process remain elusive, due to the complex and interconnected immune microenvironment within the local lesion site. In this study, the influence of Nlrp3 inflammasome-mediated immune response on the apical periodontitis was investigated. METHODOLOGY: RNA sequencing, immunohistochemistry and ELISA assay were performed to investigate the activation of Nlrp3 inflammasome signalling pathways in the human periapical tissues, including radicular cysts, periapical granulomas and healthy oral mucosa. A mouse model of apical periodontitis was established to study the role of Nlrp3 knockout in periapical bone resorption and Treg cell stability, and the underlying mechanism was explored through in vitro experiments. In vivo Treg cell adoptive transfer was performed to investigate the effects of Treg cells on the progression of apical periodontitis. RESULTS: Our findings find that the hyperactivated Nlrp3 inflammasome is present in human periapical lesions and plays a vital role in the immune-related periapical bone loss. Using a mouse model of apical periodontitis, we observe that Nlrp3 deficiency is resistant to bone resorption. This protection was accompanied by elevated generation and infiltration of local Treg cells that displayed a notable ability to suppress RANKL-dependent osteoclast differentiation. In terms of the mechanism of action, Nlrp3 deficiency directly inhibits the osteoclast differentiation and bone loss through JNK/MAPK and NF-κB pathways. In addition, Nlrp3 induces pyroptosis in the stem cells from apical papilla (SCAPs), and the subsequent release of cytokines affects the stability of Treg cell in periapical lesions, leading indirectly to enhanced bone resorption. In turn, adoptive transfer of both Nlrp3-deficient and wild-type Treg cells effectively prevent the bone erosion during apical periodontitis. CONCLUSIONS: Together, our data identify that the Nlrp3 inflammasome modulates the Treg cell stability and osteoclastogenesis in the periapical inflammatory microenvironment, thus determining the progression of bone erosion.
Assuntos
Modelos Animais de Doenças , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Periodontite Periapical , Linfócitos T Reguladores , Animais , Humanos , Camundongos , Perda do Osso Alveolar/imunologia , Perda do Osso Alveolar/metabolismo , Inflamassomos/metabolismo , Inflamassomos/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Granuloma Periapical/imunologia , Periodontite Periapical/imunologia , Periodontite Periapical/metabolismo , Cisto Radicular/imunologia , Transdução de Sinais , Linfócitos T Reguladores/imunologia , MasculinoRESUMO
V-domain Ig suppressor of T cell activation (VISTA) is a novel coinhibitory immune checkpoint molecule that maintains immune homeostasis. The present study explored the role of VISTA in human and murine inflammatory tissues of apical periodontitis (AP). VISTA was upregulated in inflammatory tissues of human AP. In mice, the expression of VISTA gradually increased with the development of mouse experimental apical periodontitis (MAP), the CD3+ T cells, CD11b+ myeloid cells, and FOXP3+ regulatory T cells also gradually accumulated. Moreover, a blockade of VISTA using a mouse in vivo anti-VISTA antibody aggravated periapical bone loss and enhanced the infiltration of immune cells in an experimental mouse periapical periodontitis model. The collective results suggest that VISTA serves as a negative regulator of the development and bone loss of apical periodontitis.
Assuntos
Perda do Osso Alveolar/metabolismo , Processo Alveolar/efeitos dos fármacos , Anticorpos/toxicidade , Proteínas de Membrana/antagonistas & inibidores , Células Mieloides/efeitos dos fármacos , Periodontite Periapical/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Adulto , Perda do Osso Alveolar/imunologia , Perda do Osso Alveolar/patologia , Processo Alveolar/imunologia , Processo Alveolar/metabolismo , Animais , Antígenos B7/metabolismo , Estudos de Casos e Controles , Modelos Animais de Doenças , Humanos , Masculino , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Células Mieloides/imunologia , Células Mieloides/metabolismo , Periodontite Periapical/imunologia , Periodontite Periapical/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Adulto JovemRESUMO
Apical periodontitis (AP) is an acute or chronic inflammatory disease caused by complex interactions between infected root canal and host immune system. It results in the induction of inflammatory mediators such as chemokines and cytokines leading to periapical tissue destruction. To understand the molecular pathogenesis of AP, we have investigated inflammatory-related genes that regulate AP development. We found here that macrophage-derived CXCL9, which acts through CXCR3, is recruited by progressed AP. The inhibition of CXCL9 by a CXCR3 antagonist reduced the lesion size in a mouse AP model with decreasing IL-1ß, IL-6 and TNFα expression. The treatment of peritoneal macrophages with CXCL9 and LPS induced the transmigration and upregulation of osteoclastogenic cytokines such as IL-1ß, IL-6 and matrix metalloprotease 2, a marker of activated macrophages. This suggests that the CXCL9-CXCR3 axis plays a crucial role in the development of AP, mediated by the migration and activation of macrophages for periapical tissue destruction. Our data thus show that CXCL9 regulates the functions of macrophages which contribute to AP pathogenesis, and that blocking CXCL9 suppresses AP progression. Knowledge of the principal factors involved in the progression of AP, and the identification of related inflammatory markers, may help to establish new therapeutic strategies.
Assuntos
Quimiocina CXCL9/metabolismo , Ativação de Macrófagos , Macrófagos/metabolismo , Periodontite Periapical/imunologia , Receptores CXCR3/metabolismo , Animais , Linhagem Celular Tumoral , Ensaios de Migração de Macrófagos , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno/imunologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Periodontite Periapical/metabolismo , Periodontite Periapical/patologia , Receptores CXCR3/antagonistas & inibidores , Raiz Dentária/patologiaRESUMO
The immune response is a complex, dynamic and strongly individual biologic network that plays an essential role in the pathogenesis of chronic apical and marginal periodontitis. Recent research in the field of periodontology has indicated that the major determinant of susceptibility to disease is the nature of the immunoinflammatory response as marginal periodontal tissue damage is thought to be primarily mediated by the host reaction. Whether the same rules apply for the development of apical periodontitis, however, remains largely unexplored. This review aims to draw parallels between the pathogenesis of chronic periodontitis of endodontic and marginal origin, outline the evidence for the destructive role of immune response in chronic marginal periodontitis and raise questions about its role in chronic apical periodontitis. It would be worthy to further explore the impact of the immune system on the characteristics and progress of these diseases and transfer some of the scientific models from the field of periodontology to the field of endodontics. Research in this area could lead to a more comprehensive understanding of the dynamics of apical and marginal periodontitis and lay the foundation of new personalized treatment strategies.
Assuntos
Imunidade Adaptativa/imunologia , Periodontite Crônica/imunologia , Imunidade Inata/imunologia , Periodontite Periapical/imunologia , HumanosRESUMO
The objective of this study was to compare the periradicular responses in endodontic infections among members of two populations: an urban Brazilian population and a non-mixed indigenous population. Samples were collected immediately and 7 days after the cleaning and shaping procedures (after reducing the intracanal microbial load) in an attempt to characterize the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-9, interferon (IFN)-γ, IL-17, IL-10, and the chemokines CXCR4, CCL2/monocyte chemotactic protein (MCP)-1, and CCR6. The endogenous cytokine and chemokine expression levels were analyzed using real-time PCR. Only the urban population showed a significant increase in TNF-α, CCL2/MCP-1, CXCR4, and CCR6 expression following the cleaning and shaping of the root canal system. The IFN-γ levels were increased at the 2nd collection (p < 0.05) in the indigenous population. In turn, a significant increase in IL-10 and IL-17 expression (p < 0.05) was observed after the cleaning and shaping procedures (2nd collection) in both populations. No significant differences in the IL-1ß, IL-9, and CCL4 expression levels were observed between the 1st and 2nd collections in both populations. The results demonstrate a cytokine and chemokine expression profile that is specific to each analyzed population. However, immune modulation mediated by IL-10 began on the 7th day after the beginning of the endodontic treatment in both populations.
Assuntos
Necrose da Polpa Dentária/genética , Necrose da Polpa Dentária/imunologia , Periodontite Periapical/genética , Periodontite Periapical/imunologia , Brasil , Citocinas/análise , Regulação da Expressão Gênica , Humanos , Fenômenos do Sistema Imunitário , Indígenas Sul-Americanos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Tratamento do Canal Radicular/métodos , Estatísticas não Paramétricas , Fatores de Tempo , População UrbanaRESUMO
Cytokines and chemokines have a fundamental role in the maintenance of inflammation and bone response, which culminate in the development of chronic periapical lesions. Regulatory (Treg) and Th17 cytokines play a key role in regulating the immune response involved in this process. The aim of this study was to investigate the role of Treg and Th17 cells in chronic inflammatory periapical disease, by comparing the expression of the immunoregulatory mediators TGF-ß, IL-10, CCL4, and the proinflammatory IL-17 and CCL20 in the periapical tissue of teeth with pulp necrosis, with and without associated chronic lesions. Eighty-six periapical tissue samples were obtained from human teeth. The samples were divided into three groups: pulp necrosis with a periapical lesion (n=26); pulp necrosis without a periapical lesion (n=30), and control (n=30). All samples were submitted to histopathological analysis and cytokine and chemokine measurement through ELISA. Statistical analyses were done with Kruskal-Wallis and Mann-Whitney tests and Spearman correlation. The group with pulp necrosis and a periapical lesion showed a higher expression of CCL4 and TGF-ß in comparison with pulp necrosis without a lesion. CCL20 was higher in the group with a periapical lesion when compared to the control. In all groups there was a weak positive correlation between IL-17/CCL20, IL-10/CCL4, and IL-17/TGF-ß. Both types of cytokines, pro-inflammatory and immunoregulatory, occur simultaneously in periapical tissue. However, a rise in immunosuppressive cytokines and chemokines (CCL4 and TGF-ß) in periapical lesions suggests a role of these cytokines in stable periapical disease.
Assuntos
Quimiocinas CC/análise , Interleucinas/análise , Periodontite Periapical/patologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Fator de Crescimento Transformador beta/análise , Adulto , Estudos de Casos e Controles , Quimiocinas CC/imunologia , Doença Crônica , Necrose da Polpa Dentária/imunologia , Necrose da Polpa Dentária/patologia , Humanos , Interleucinas/imunologia , Pessoa de Meia-Idade , Periodontite Periapical/imunologia , Valores de Referência , Estatísticas não Paramétricas , Fator de Crescimento Transformador beta/imunologia , Adulto JovemRESUMO
INTRODUCTION: Apical periodontitis (AP), except for the local known consequences, may also be a systemic burden. Circulating inflammatory mediators that are released to sustain the AP lesion can in theory harm other bodily tissues. The aim of this systematic review was to summarize the existing evidence on the influence of AP on the peripheral blood levels of inflammatory mediators and markers of systemic stress. METHODS: A search of MEDLINE-PubMed, Embase, and Cochrane was conducted up to and including February 2019 to identify studies in 5 different languages. The Newcastle-Ottawa Scale was used for quality assessment of the included studies. RESULTS: Twelve of the 20 included studies were case-control studies, and 8 were intervention studies. The data of all the included studies were analyzed descriptively, whereas the data of 11 studies were available for meta-analyses. The study designs were heterogeneous. Nevertheless, the meta-analyses revealed statistically significant differences in C-reactive protein, interleukin 6, and asymmetric dimethylarginine levels between AP subjects and controls in peripheral blood. In addition, the concentration of C3 complement fragment in peripheral blood was significantly lower after the treatment and resolution of AP than before. CONCLUSIONS: The existing literature indicates that AP adds on to systemic inflammation by elevating C-reactive protein, interleukin 6, asymmetric dimethylarginine, and C3 levels. In order to overcome the issue of large variation between study designs, future studies should have clear inclusion criteria, preferably larger cohorts, adequate follow-up of all subjects, and a thorough presentation of the data to enable further exploration of the possible burden of AP on general human health. Nevertheless, there is now stronger evidence that AP contributes to low-grade systemic inflammation.
Assuntos
Mediadores da Inflamação , Inflamação , Periodontite Periapical , Proteína C-Reativa , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Periodontite Periapical/imunologia , Periodontite Periapical/metabolismoRESUMO
INTRODUCTION: Dental cysts can be of inflammatory (radicular cysts) or noninflammatory (dentigerous cysts) origin. Apical periodontitis is a necrosis of the pulp and infection of the root canal causing the development of apical granulomas or radicular cysts. The immunology of granuloma and cyst formation is important because modern root filling materials are immunologically active and can contribute to the resolution of apical granulomas. In contrast, radicular cysts often require apicectomy. A better understanding of the pathophysiology of inflammation and bone resorption in apical periodontitis could be the basis for developing new root filling materials with superior immunomodulatory properties. METHODS: Forty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray of the 87 consecutive specimens was created, and human leukocyte antigen-DR isotype (HLA-DR)-, CD83-, receptor activator of nuclear factor kappa B ligand-, macrophage colony-stimulating factor (MCSF)-, galectin-3 (Gal3)-, CD4-, and CD8-positive cells were detected by immunohistochemistry. Tissue microarrays were digitized, and the expression of markers was quantitatively assessed. RESULTS: HLA-DR, CD83, MCSF, and Gal3 expression was significantly (P < .05) higher in radicular cysts compared with apical granulomas. HLA-DR, CD83, MCSF, receptor activator of nuclear factor kappa B ligand, and Gal3 expression in dentigerous cysts was significantly (P < .05) lower than in both periapical lesions (apical granulomas and radicular cysts). CD4 and CD8 infiltration was not statistically different between apical granulomas and radicular cysts. Dentigerous cysts showed a significantly (P < .05) lower T-cell infiltration than apical periodontitis. The CD4/CD8 ratio was not significantly different between the analyzed groups. CONCLUSIONS: The development of radicular cysts in apical periodontitis is associated with an increased expression of myeloid inflammatory markers and bone resorption parameters. Antigen-presenting cells and myeloid cells might be more relevant for the pathogenesis of apical periodontitis than T cells. Increased inflammation might promote the formation of radicular cysts and more pronounced bone resorption.
Assuntos
Reabsorção Óssea , Cisto Dentígero , Inflamação , Granuloma Periapical , Periodontite Periapical , Cisto Radicular , Reabsorção Óssea/imunologia , Cisto Dentígero/imunologia , Granuloma , Humanos , Granuloma Periapical/imunologia , Periodontite Periapical/imunologia , Cisto Radicular/imunologiaRESUMO
Locally produced osteoclastogenic factor RANKL plays a critical role in the development of bone resorption in periradicular periodontitis. However, because RANKL is also required for healthy bone remodeling, it is plausible that a costimulatory molecule that upregulates RANKL production in inflammatory periradicular periodontitis may be involved in the pathogenic bone loss processes. We hypothesized that macrophage migration inhibitory factor (MIF) would play a role in upregulating the RANKL-mediated osteoclastogenesis in the periradicular lesion. In response to pulp exposure, the bone loss and level of MIF mRNA increased in the periradicular periodontitis, which peaked at 14 d, in conjunction with the upregulated expressions of mRNAs for RANKL, proinflammatory cytokines (TNF-α, IL-6, and IL-1ß), chemokines (MCP-1 and SDF-1), and MIF's cognate receptors CXCR4 and CD74. Furthermore, expressions of those mRNAs were found significantly higher in wild-type mice compared with that of MIF-/- mice. In contrast, bacterial LPS elicited the production of MIF from ligament fibroblasts in vitro, which, in turn, enhanced their productions of RANKL and TNF-α. rMIF significantly upregulated the number of TRAP+ osteoclasts in vitro. Finally, periapical bone loss induced in wild-type mice were significantly diminished in MIF-/- mice. Altogether, the current study demonstrated that MIF appeared to function as a key costimulatory molecule to upregulate RANKL-mediated osteoclastogenesis, leading to the pathogenically augmented bone resorption in periradicular lesions. These data also suggest that the approach to neutralize MIF activity may lead to the development of a therapeutic regimen for the prevention of pathogenic bone loss in periradicular periodontitis.
Assuntos
Reabsorção Óssea/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Periodontite Periapical/metabolismo , Animais , Reabsorção Óssea/imunologia , Modelos Animais de Doenças , Inflamação/imunologia , Inflamação/metabolismo , Fatores Inibidores da Migração de Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Periodontite Periapical/imunologia , Ligante RANK/imunologia , Ligante RANK/metabolismoRESUMO
AIM: To investigate the DNA methylation profiles of immune response-related genes in apical periodontitis (AP) lesions. METHODOLOGY: The methylation profiles on the cytosine-phosphate-guanine (CpG) regions of 22 gene promoters involved in inflammation and autoimmunity were assessed in 60 human AP lesions and 24 healthy periodontal ligaments (controls) using a pathway-specific real-time polymerase chain reaction array (EpiTect® Methyl Signature PCR Array Human Inflammatory Response). Differentially methylated genes were subsequently assessed for their mRNA expression. Data analyses (One-way anova, Tukey's multiple comparisons tests and Mann-Whitney tests) were performed using GraphPad Prism 6 software. P values ≤ 0.05 were considered statistically significant. RESULTS: Significant DNA hypermethylation was observed for CXCL3 and FADD gene promoters in AP lesions when compared to control tissues (P < 0.001) and among other genes (P < 0.05). In contrast, IL12B and IL4R were associated with significant hypomethylation in comparison to other genes (P < 0.05). IL12B, IL4R, CXCL3 and FADD had differential mRNA expression in AP lesions and controls (P < 0.001). CONCLUSIONS: Differential methylation profiles of immune response-related genes, such as FADD, CXCL3, IL12B and IL4R, may have an influence on individual AP susceptibility and patient treatment outcomes, through their potential contributions to altered expression of disease-relevant genes. Methylation and/or genetic variations in additional genes may also contribute to the dynamics of AP development and should be considered in future studies.
Assuntos
Metilação de DNA , Periodontite Periapical/genética , Periodontite Periapical/imunologia , Periodontite Periapical/metabolismo , Transcriptoma , Adolescente , Adulto , Idoso , Autoimunidade/genética , Brasil , Quimiocinas/genética , Quimiocinas CXC/genética , Citocinas/genética , Proteína de Domínio de Morte Associada a Fas/genética , Regulação da Expressão Gênica , Humanos , Inflamação , Subunidade p40 da Interleucina-12/genética , Subunidade alfa de Receptor de Interleucina-4/genética , Pessoa de Meia-Idade , Ligamento Periodontal , Regiões Promotoras Genéticas , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Citocinas/genética , Adulto JovemRESUMO
AIM: To determine if bacteria associated with persistent apical periodontitis induce species-specific pro-inflammatory cytokine responses in macrophages, and the effects of this species-specific microenvironment on osteogenic differentiation. METHODOLOGY: Macrophages were exposed to Enterococcus faecalis, Streptococcus oralis, Streptococcus mitis, Fusobacterium nucleatum, Treponema denticola or Tannerella forsythia, and levels of TNF-α and IL-1ß elicited were determined by immunoassay. Following treatment of MG-63 pre-osteoblasts with conditioned media from bacteria-exposed macrophages, osteogenic differentiation and viability of osteoblasts were analyzed by Alizarin Red Staining and MTS assay, respectively. Statistical analysis was carried out by one-way anova with the Tukey post-hoc test. Differences were considered to be significant if P < 0.05. RESULTS: Macrophages exposed to Gram-positive bacteria did not produce significant amounts of cytokines. F. nucleatum-challenged macrophages produced up to four-fold more TNF-α and IL-1ß compared to T. denticola or T. forsythia. Only conditioned media from macrophages treated with Gram-negative bacteria decreased mineralization and viability of osteoblasts. CONCLUSIONS: Gram-positive bacteria did not impact osteogenic differentiation and appeared innocuous. Gram-negative bacteria, in particular F. nucleatum elicited an enhanced pro-inflammatory response in macrophages, inhibited osteogenic differentiation and reduced cell viability. The findings suggest that the presence of this organism could potentially increase the severity of persistent apical periodontitis.
Assuntos
Bactérias/classificação , Diferenciação Celular , Citocinas/metabolismo , Osteogênese , Periodontite Periapical/imunologia , Periodontite Periapical/microbiologia , Calcificação Fisiológica , Sobrevivência Celular , Enterococcus faecalis/patogenicidade , Fusobacterium nucleatum/patogenicidade , Expressão Gênica , Humanos , Inflamação/microbiologia , Interleucina-1beta/metabolismo , Macrófagos/imunologia , Macrófagos/microbiologia , Osteoblastos , Periodontite Periapical/patologia , Especificidade da Espécie , Streptococcus mitis/patogenicidade , Streptococcus oralis/patogenicidade , Tannerella forsythia/patogenicidade , Treponema denticola/patogenicidade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Abstract Cytokines and chemokines have a fundamental role in the maintenance of inflammation and bone response, which culminate in the development of chronic periapical lesions. Regulatory (Treg) and Th17 cytokines play a key role in regulating the immune response involved in this process. The aim of this study was to investigate the role of Treg and Th17 cells in chronic inflammatory periapical disease, by comparing the expression of the immunoregulatory mediators TGF-β, IL-10, CCL4, and the proinflammatory IL-17 and CCL20 in the periapical tissue of teeth with pulp necrosis, with and without associated chronic lesions. Eighty-six periapical tissue samples were obtained from human teeth. The samples were divided into three groups: pulp necrosis with a periapical lesion (n=26); pulp necrosis without a periapical lesion (n=30), and control (n=30). All samples were submitted to histopathological analysis and cytokine and chemokine measurement through ELISA. Statistical analyses were done with Kruskal-Wallis and Mann-Whitney tests and Spearman correlation. The group with pulp necrosis and a periapical lesion showed a higher expression of CCL4 and TGF-β in comparison with pulp necrosis without a lesion. CCL20 was higher in the group with a periapical lesion when compared to the control. In all groups there was a weak positive correlation between IL-17/CCL20, IL-10/CCL4, and IL-17/TGF-β. Both types of cytokines, pro-inflammatory and immunoregulatory, occur simultaneously in periapical tissue. However, a rise in immunosuppressive cytokines and chemokines (CCL4 and TGF-β) in periapical lesions suggests a role of these cytokines in stable periapical disease.
Assuntos
Humanos , Adulto , Adulto Jovem , Periodontite Periapical/patologia , Fator de Crescimento Transformador beta/análise , Interleucinas/análise , Linfócitos T Reguladores/imunologia , Quimiocinas CC/análise , Células Th17/imunologia , Periodontite Periapical/imunologia , Valores de Referência , Estudos de Casos e Controles , Doença Crônica , Fator de Crescimento Transformador beta/imunologia , Interleucinas/imunologia , Estatísticas não Paramétricas , Necrose da Polpa Dentária/imunologia , Necrose da Polpa Dentária/patologia , Quimiocinas CC/imunologia , Pessoa de Meia-IdadeRESUMO
The purpose of this manuscript was to re-discuss apical periodontitis, apical biofilm, and its possible relationship with dendritic cells (DC). DCs are potent regulators of the immune system and their function is divided into three categories that involve the presentation of antigens: the presentation of antigens and activation of T cells; a not well established category suggested that DCs induce and maintain immunological tolerance; and the maintenance of the immune memory in conjunction with B cells. DCs in periapical inflammatory lesions are composed of at least two subpopulations that can be distinguished on the basis of ultrastructure and phenotype. These populations might differ in lineage, state of maturation, differentiation, activation, and/or function. The authors hereby analyzed the root apexes of teeth under SEM, after performing apicoectomy due to the failure of conventional endodontic treatment. Microbial biofilm with multispecies and areas of resorption with the presence of Howship lacunae, and images suggestive of denditric cells could be observed. The presence of DCs in periapical lesion could be an indication of the severity of the lesion, with a constant presence of antigen in the periradicular region.
Assuntos
Biofilmes , Células Dendríticas/patologia , Periodontite Periapical/microbiologia , Periodontite Periapical/patologia , Antígenos/imunologia , Células Dendríticas/imunologia , Humanos , Microscopia Eletrônica de Varredura , Periodontite Periapical/imunologia , Linfócitos T/imunologia , Linfócitos T/microbiologiaRESUMO
OBJECTIVES: Apical periodontitis can appear clinically as apical granulomas or radicular cysts. There is evidence that immunologic factors are involved in the pathogenesis of both pathologies. In contrast to radicular cysts, the dentigerous cysts have a developmental origin. Macrophage polarization (M1 vs M2) is a main regulator of tissue homeostasis and differentiation. There are no studies comparing macrophage polarization in apical granulomas, radicular cysts, and dentigerous cysts. MATERIALS AND METHODS: Forty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray (TMA) of the 87 consecutive specimens was created, and CD68-, CD11c-, CD163-, and MRC1-positive macrophages were detected by immunohistochemical methods. TMAs were digitized, and the expression of macrophage markers was quantitatively assessed. RESULTS: Radicular cysts are characterized by M1 polarization of macrophages while apical granulomas show a significantly higher degree of M2 polarization. Dentigerous cysts have a significantly lower M1 polarization than both analyzed periapical lesions (apical granulomas and radicular cysts) and accordingly, a significantly higher M2 polarization than radicular cysts. Macrophage cell density in dentigerous cysts is significantly lower than in the periapical lesions. CONCLUSIONS: The development of apical periodontitis towards apical granulomas or radicular cysts might be directed by macrophage polarization. Radicular cyst formation is associated with an increased M1 polarization of infiltrating macrophages. In contrast to radicular cysts, dentigerous cysts are characterized by a low macrophage infiltration and a high degree of M2 polarization, possibly reflecting their developmental rather than inflammatory origin. CLINICAL RELEVANCE: As M1 polarization of macrophages is triggered by bacterial antigens, these results underline the need for sufficient bacterial clearance during endodontic treatment to prevent a possible M1 macrophage-derived stimulus for radicular cyst formation.
Assuntos
Cisto Dentígero/imunologia , Macrófagos/imunologia , Granuloma Periapical/imunologia , Periodontite Periapical/imunologia , Cisto Radicular/imunologia , Contagem de Células , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
5-Lipoxygenase (5-LO) plays a vital role in the host innate immune response, including bacteria-induced inflammation. Apical periodontitis (AP) is due to immune disorders caused by imbalances between bacterial invasion and subsequent host defense response. In this work, we investigated the role of 5-lipoxygenase in AP by using 5- lo knockout mice (5- lo-/- mice). Results showed that 5- lo-/- mice had greater periapical bone loss and more osteoclasts positive for tartrate-resistant acid phosphatase staining than did wild-type mice, as determined by micro-computed tomography and histologic staining. The inflammation- and osteoclastogenesis-related factors IL-1ß, TNF-α, RANK, and RANKL were also significantly elevated in 5- lo-/- mice, whereas osteoprotegerin was reduced. Furthermore, peritoneal macrophages from 5- lo-/- mice revealed an obviously impaired ability to phagocytose the AP pathogenic bacteria Fusobacterium nucleatum. In vivo experiments confirmed that 5- lo knockout led to decreased macrophage recruitment and increased F. nucleatum infection around the periapical area due to decreased leukotriene B4 and LXA4 production. All these results showed that 5- lo knockout impaired the host innate immune system to promote the release of bone resorption-related factors. Therefore, 5- lo deficiency aggravated AP in an experimental murine AP model.
Assuntos
Araquidonato 5-Lipoxigenase/imunologia , Periodontite Periapical/enzimologia , Periodontite Periapical/imunologia , Animais , Western Blotting , Citocinas/imunologia , Modelos Animais de Doenças , Imunofluorescência , Fusobacterium nucleatum , Imunidade Inata , Leucotrieno B4/imunologia , Masculino , Camundongos , Camundongos Knockout , Osteoclastos/enzimologia , Osteoclastos/imunologia , Fagocitose/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Fosfatase Ácida Resistente a Tartarato/imunologia , Microtomografia por Raio-XRESUMO
Abstract: The purpose of this manuscript was to re-discuss apical periodontitis, apical biofilm, and its possible relationship with dendritic cells (DC). DCs are potent regulators of the immune system and their function is divided into three categories that involve the presentation of antigens: the presentation of antigens and activation of T cells; a not well established category suggested that DCs induce and maintain immunological tolerance; and the maintenance of the immune memory in conjunction with B cells. DCs in periapical inflammatory lesions are composed of at least two subpopulations that can be distinguished on the basis of ultrastructure and phenotype. These populations might differ in lineage, state of maturation, differentiation, activation, and/or function. The authors hereby analyzed the root apexes of teeth under SEM, after performing apicoectomy due to the failure of conventional endodontic treatment. Microbial biofilm with multispecies and areas of resorption with the presence of Howship lacunae, and images suggestive of denditric cells could be observed. The presence of DCs in periapical lesion could be an indication of the severity of the lesion, with a constant presence of antigen in the periradicular region.
Assuntos
Humanos , Periodontite Periapical/microbiologia , Periodontite Periapical/patologia , Células Dendríticas/patologia , Biofilmes , Periodontite Periapical/imunologia , Células Dendríticas/imunologia , Microscopia Eletrônica de Varredura , Linfócitos T/imunologia , Linfócitos T/microbiologia , Antígenos/imunologiaRESUMO
The process involved in periapical lesions, which occur as an outcome of pulpal necrosis, is regulated by the immune system including regulatory T cells (Treg) and T helper 17 cell (Th17) responses. The objective of this study was to conduct a frequency systematic review to determine the presence of Treg/Th17 responses and the influence of these cells in the progression of chronic inflammatory periapical lesions in humans. A systematic computerized search was carried out in Pubmed, Medline, Web of Science and Scopus electronic databases from their date of inception through the first week of May 2017. In addition, the reference lists of the included articles and the grey literature were hand-searched. Articles that evaluated the presence and influence of Treg/Th17 in the progression of human periapical lesions were included. Study selection and the quality assessment of the included articles (using the Newcastle-Ottawa scale) were carried out by two authors. Fifty-seven titles/abstracts were screened and eight studies met the eligibility criteria and were included in this systematic review. The included studies showed large variation in the type of periapical lesion assessed, mean age, age range, type of experiment and findings regarding the participation of Th17 and Treg in the status of inflammatory periapical lesions. The studies showed the involvement of Treg in the modulation of the inflammatory response in radicular cysts and periapical granulomas. This systematic review highlights the relationship between Treg and Th17 acting in a subtle balance inhibiting or promoting the progression of human periapical lesions.
Assuntos
Periodontite Periapical/patologia , Linfócitos T Reguladores/patologia , Células Th17/patologia , Doença Crônica , Citocinas/análise , Progressão da Doença , Fatores de Transcrição Forkhead/análise , Humanos , Periodontite Periapical/imunologia , Viés de Publicação , Linfócitos T Reguladores/imunologia , Células Th17/imunologiaRESUMO
OBJECTIVES: To evaluate the CD68 immunoexpression in post-treatment apical periodontitis lesions of older patients and compare them with lesions of younger/middle age adults. METHODS: Biopsy specimens from 21 apical periodontitis lesions (12 granulomas and 9 cysts) were selected from older patients and 25 apical periodontitis lesions from younger/middle age adults (12 cysts and 13 granulomas) were selected and analyzed by immunohistochemistry using silanized slides with anti-CD68 antibody. The slides were subdivided in five high-power fields and the images were observed under an optical microscope to evaluate the epithelial and connective tissues. RESULTS: The results showed that there was no statistical difference for the CD68 expression in epithelial tissue of cysts between younger/middle age adults and older patients. However, for the connective tissue of both cysts and granulomas, there was a statistical difference between the two age groups. There was a statistical difference between the epithelial and the connective tissues in cysts of younger/middle age adults, and also when the epithelial tissue of the cysts was compared with connective tissue of the granuloma. In the group of older patients, there was no statistical difference between the connective tissue of the cysts and granulomas. CONCLUSION: The intensity of the macrophage staining was greater in the connective tissue of cysts and granulomas alike in the younger/middle age adult patients, suggesting that these cells participate actively in this tissue. Immune responses in older patients may be compromised, suggesting that there is a greater tendency for the endodontic treatment of these patients to fail.
Assuntos
Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Macrófagos/imunologia , Periodontite Periapical/imunologia , Periodontite Periapical/terapia , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
The aim of the study was to define local immune and oxidative changes in patients with exacerbated chronic apical periodontitis. These changes were assessed in saliva of 67 patients with the mean age of 31±2.5 before and after treatment. The study revealed disturbances in cytokines and complement system balance and activation of lipids peroxidation. Combination of Gepon or Vobenzim with Essentiale forte H and Kaskatol proved to be the most effective for correction of this imbalance.
Assuntos
Periodontite Crônica/imunologia , Periodontite Crônica/metabolismo , Estresse Oxidativo , Periodontite Periapical/imunologia , Periodontite Periapical/metabolismo , Adjuvantes Imunológicos/uso terapêutico , Adulto , Antioxidantes/uso terapêutico , Periodontite Crônica/tratamento farmacológico , Proteínas do Sistema Complemento/imunologia , Citocinas/imunologia , Progressão da Doença , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Hidrolases/uso terapêutico , Peroxidação de Lipídeos , Masculino , Oligopeptídeos/uso terapêutico , Periodontite Periapical/tratamento farmacológico , Fosfatidilcolinas/uso terapêutico , Rutina/uso terapêuticoRESUMO
Abstract: The process involved in periapical lesions, which occur as an outcome of pulpal necrosis, is regulated by the immune system including regulatory T cells (Treg) and T helper 17 cell (Th17) responses. The objective of this study was to conduct a frequency systematic review to determine the presence of Treg/Th17 responses and the influence of these cells in the progression of chronic inflammatory periapical lesions in humans. A systematic computerized search was carried out in Pubmed, Medline, Web of Science and Scopus electronic databases from their date of inception through the first week of May 2017. In addition, the reference lists of the included articles and the grey literature were hand-searched. Articles that evaluated the presence and influence of Treg/Th17 in the progression of human periapical lesions were included. Study selection and the quality assessment of the included articles (using the Newcastle-Ottawa scale) were carried out by two authors. Fifty-seven titles/abstracts were screened and eight studies met the eligibility criteria and were included in this systematic review. The included studies showed large variation in the type of periapical lesion assessed, mean age, age range, type of experiment and findings regarding the participation of Th17 and Treg in the status of inflammatory periapical lesions. The studies showed the involvement of Treg in the modulation of the inflammatory response in radicular cysts and periapical granulomas. This systematic review highlights the relationship between Treg and Th17 acting in a subtle balance inhibiting or promoting the progression of human periapical lesions.