RESUMO
Inflammatory radicular cysts (IRCs) are chronic lesions that follow the development of periapical granulomas (PGs). IRCs result from multiple inflammatory reactions led initially by several pro-inflammatory interleukins and growth factors that provoke the proliferation of epithelial cells derived from epithelial cell rests of Malassez present in the granulomatous tissue, followed by cyst formation and growth processes. Multiple theories have been proposed to help explain the molecular process involved in the development of the IRC from a PG. However, although multiple studies have demonstrated the presence of epithelial cells in most PGs, it is still not fully understood why not all PGs turn into IRCs, even though both are stages of the same inflammatory phenomenon and receive the same antigenic stimulus. Histopathological examination is currently the diagnostic gold standard for differentiating IRCs from PGs. Although multiple studies have evaluated the accuracy of non-invasive or minimally invasive methods in assessing the histopathological nature of the AP before the intervention, these studies' results are still controversial. This narrative review addresses the biological insights into the complex molecular mechanisms of IRC formation and its histopathological features. In addition, the relevant inflammatory molecular mediators for IRC development and the accuracy of non-invasive or minimally invasive diagnostic approaches are summarised. (EEJ-2022-03-041).
Assuntos
Granuloma Periapical , Cisto Radicular , Humanos , Cisto Radicular/diagnóstico , Cisto Radicular/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Inflamação/patologia , Granuloma Periapical/metabolismo , Granuloma Periapical/patologia , Peptídeos e Proteínas de Sinalização IntercelularRESUMO
INTRODUCTION: The balance between the host proinflammatory immune response and the counteracting anti-inflammatory and reparative responses supposedly determine the outcome of periapical lesions. In this scenario, the vasoactive intestinal peptide (VIP) may exert a protective role because of its prominent immunoregulatory capacity. In this study, we investigated (in a cause-and-effect manner) the potential involvement of VIP in the development of human and experimental periapical lesions. METHODS: Periapical granulomas (n = 124) and control samples (n = 48) were comparatively assessed for VIP and multiple immunologic/activity marker expression through real-time polymerase chain reaction. Experimental periapical lesions (C57Bl/6 wild-type mice) were evaluated regarding endogenous VIP expression correlation with lesion development and the effect of recombinant VIP therapy in lesion outcome. CCR4KO and IL4KO strains and anti-glucocorticoid-induced TNFR-related protein inhibition were used to test the involvement of Treg and Th2 cells in VIP-mediated effects. RESULTS: VIP expression was more prevalent in periapical granulomas than in controls, presenting a positive association with immunoregulatory factors and an inverse association/correlation with proinflammatory mediators and the receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio. Endogenous VIP expression up-regulation was temporally associated with lesion immunoregulation and a decline of bone loss. VIP therapy in mice prompted the arrest of lesion development, being associated with an anti-inflammatory and proreparative response that limits the proinflammatory, Th1, Th17, and osteoclastogenic response in the periapex. The VIP protective effect was dependent of Treg migration and activity and independent of interleukin 4. CONCLUSIONS: Our results show that VIP overexpression in human and experimental periapical lesions is associated with lesion inactivity and that VIP therapy results in the attenuation of experimental lesion progression associated with the immunosuppressive response involving Treg cells.
Assuntos
Granuloma Periapical , Peptídeo Intestinal Vasoativo , Animais , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Granuloma Periapical/metabolismo , Linfócitos T Reguladores , Células Th17 , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
INTRODUCTION: The purpose of this study was to evaluate the expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor alpha (TNF-α) in periapical granuloma (PG) and radicular cyst (RC) samples and to correlate it with the type of lesion, the intensity of the inflammatory infiltrate, and the thickness of the epithelial lining. METHODS: A total of 51 cases of periapical lesions (25 PGs and 26 RCs) were subjected to morphologic analysis and immunohistochemical study. The anti-COX-2 and anti-TNF-α antibodies were applied using the immunoperoxidase technique. Data were analyzed by the Mann-Whitney test, Pearson chi-square test, Fisher exact test, and Spearman correlation. RESULTS: Analysis of the inflammatory infiltrate revealed that 80% of PGs exhibited a grade III infiltrate as opposed to a 19% rate in RCs (P < .001). Morphologic evaluation of the epithelial thickness of RCs revealed the presence of atrophic epithelium in 73% of cases. The majority of PGs had a score of 1 for COX-2 immunoexpression (n = 14, 54%) and a score of 2 for TNF-α expression (n = 16, 64%), whereas in cases of RCs a score of 1 was more prevalent for COX-2 and TNF-α expression (n = 17, 65%). Significant differences in the expression scores of COX-2 and TNF-α were detected in periapical lesions (P < .001). CONCLUSIONS: Based on these findings, we emphasize that RCs and PGs have a similar expression of inflammatory mediators (COX-2 and TNF-α) although the secretion of TNF-α by macrophages and of COX-2 by several cells was higher in PGs, indicating a greater inflammatory response in these lesions.
Assuntos
Ciclo-Oxigenase 2/metabolismo , Imuno-Histoquímica/métodos , Mediadores da Inflamação/metabolismo , Granuloma Periapical/metabolismo , Tecido Periapical/metabolismo , Cisto Radicular/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ciclo-Oxigenase 2/genética , Feminino , Expressão Gênica , Humanos , Macrófagos/metabolismo , Masculino , Granuloma Periapical/patologia , Tecido Periapical/patologia , Cisto Radicular/patologia , Fator de Necrose Tumoral alfa/genéticaRESUMO
INTRODUCTION: The aim of the present study was to compare the immunoexpression of CD34, intercellular adhesion molecule-1 (ICAM-1), and podoplanin and the presence of mast cells with clinical, demographic, radiologic, and histologic features from periapical granulomas, periapical cysts, and residual cysts. METHODS: Thirty-one lesions (5 granulomas, 15 periapical cysts, and 11 residual cysts) were selected. Histologic sections in silanized slides were used for the immunohistochemical reactions. The analysis of the images was performed by using an optical microscope, and data were analyzed with 5% significance (P < .05). RESULTS: Cysts presented atrophic and hyperplastic epithelium in 11 cases (35.5%) and 15 cases (48.8%), respectively (P > .05). The intensity of the inflammatory infiltrate was similar when comparing the 3 groups (P > .05). CD34 and podoplanin expression and the presence of mast cells were similar when comparing the 3 groups; ICAM-1 expression was more intense in granulomas than cysts (P < .05). There were no statistically significant differences associated with the expression of the evaluated markers according to the intensity of the inflammatory infiltrate. CONCLUSIONS: There were no differences in the expression of CD34 and podoplanin and in the presence of mast cells when the 3 groups were compared. ICAM-1 expression was more common in periapical granulomas.
Assuntos
Antígenos CD34/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Mastócitos/metabolismo , Glicoproteínas de Membrana/metabolismo , Doenças Periapicais/metabolismo , Granuloma Periapical/metabolismo , Cisto Radicular/metabolismo , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Mastócitos/patologia , Pessoa de Meia-Idade , Doenças Periapicais/patologia , Granuloma Periapical/patologia , Tecido Periapical/metabolismo , Tecido Periapical/patologia , Cisto Radicular/patologia , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: Galectins play important roles in immunoinflammatory responses, but their participation in the development of periapical lesions remains unclear. This study aimed to evaluate the expressions of galectins-1, -3, and -7 in periapical lesions, correlating them with the intensity of the inflammatory infiltrate and the pattern of the cystic epithelium. METHODS: Twenty periapical granulomas (PGs), 20 radicular cysts (RCs), and 20 residual radicular cysts (RRCs) were submitted to immunohistochemistry using anti-galectin-1, -3, and -7 antibodies. The percentage of immunopositive cells in epithelial and connective tissues was determined. RESULTS: In connective tissue, PGs exhibited higher cytoplasmic/membrane expression of galectins-1 and -7 than RCs and RRCs (P < .05). There was higher nuclear expression of galectin-1 in PGs compared with RCs and RRCs (P < .05). The expression of galectins-1 and -7 in connective tissue was higher in lesions with grade III inflammation (P < .05). No significant differences in galectin-3 immunoexpression were observed for any of the parameters evaluated (P > .05). In the epithelial component, a higher nuclear expression of galectin-7 was detected in RRCs (P < .05), and a higher cytoplasmic/membrane expression of this protein was found in cysts with hyperplastic epithelium (P < .05). Positive correlations were observed between the nuclear and cytoplasmic/membrane expression of galectin-1 in connective tissue (P < .05) as well as between the nuclear and cytoplasmic/membrane expression of galectin-7 in epithelial tissue of cysts (P < .05). CONCLUSIONS: Galectins-1 and -7 may play important roles in the pathogenesis of PGs, RCs, and RRCs. On the other hand, the present results suggest only a minor involvement of galectin-3 in the development of these lesions.
Assuntos
Galectina 1/metabolismo , Galectina 3/metabolismo , Galectinas/metabolismo , Doenças Periapicais/patologia , Granuloma Periapical/patologia , Cisto Radicular/patologia , Humanos , Doenças Periapicais/metabolismo , Granuloma Periapical/metabolismo , Tecido Periapical/metabolismo , Tecido Periapical/patologia , Cisto Radicular/metabolismoRESUMO
The objective of this study was to evaluate the expression of matrix metalloproteinase 9 (MMP-9) and transforming growth factor beta (TGF-ß1) in periapical lesion samples correlated with the intensity of the inflammatory infiltrate and thickness of the epithelial lining. Forty-five cases of periapical lesions (23 periapical granulomas and 22 radicular cysts) were subjected to morphological and immunohistochemical analyses using anti-MMP-9 and anti-TGF-ß1 antibodies. The data were analyzed using the following tests: non-parametric Mann-Whitney, chi-square, Fisher's exact test and Spearman's correlation test (P<0.05). Analysis of inflammatory infiltrate revealed that 78% of periapical granulomas presented infiltrate grade III, in contrast with 32% of radicular cysts (P<0.001). Morphological evaluation of the epithelial thickness in radicular cysts revealed the presence of atrophic epithelium in 86% of the cysts. The immunostaining of MMP-9 was score 2 in 67% of the granulomas and 77% of the cysts. Both lesions were predominantly score 1 for TGF-ß1. Significant differences were confirmed between the expression scores of TGF-ß1 and MMP-9 in periapical granulomas (p = 0.004) and in radicular cysts (p < 0.001). Expression of TGF-ß1 was different for periapical granulomas and radicular cysts. This immunoregulatory cytokine seems more representative in asymptomatic lesions. The extracellular matrix remodeling process dependent on MMP-9 seems to be similar for both periapical granulomas and radicular cysts. TGF-ß1 and MMP-9 may play an important role in the maintenance of periapical lesions.
Assuntos
Metaloproteinase 9 da Matriz/análise , Granuloma Periapical/metabolismo , Cisto Radicular/química , Fator de Crescimento Transformador beta1/análise , Adulto , Biópsia , Células Epiteliais/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Granuloma Periapical/imunologia , Granuloma Periapical/patologia , Cisto Radicular/imunologia , Cisto Radicular/patologia , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
The objective of this study was to observe the distribution of macrophages (MPs) expressing transforming growth factor beta-1 (TGF-ß1) in tissue samples from patients with different human chronic periapical diseases. In this study, samples were collected from 75 volunteers, who were divided into three groups according to classified standards, namely, healthy control (N = 25), periapical granuloma (N = 25), and periapical cyst (N = 25). The samples were fixed in 10% buffered formalin for more than 48 h, dehydrated, embedded, and stained with hematoxylin and eosin for histopathology. Double immunofluorescence was conducted to analyze the expression of TGF-ß-CD14 double-positive MPs in periapical tissues. The number of double-positive cells (cells/mm2) were significantly higher in the chronic periapical disease tissues (P < 0.01) compared to that in the control tissue; in addition, the density of TGF-ß1-CD14 double positive cells was significantly higher in the periapical cyst group than in the periapical granuloma group (P < 0.01). The number of TGF-ß1 expressing macrophages varied with human chronic periapical diseases. The TGF-ß1-CD14 double-positive cells might play an important role in the pathology of human chronic periapical diseases.
Assuntos
Macrófagos/metabolismo , Doenças Periapicais/metabolismo , Fator de Crescimento Transformador beta1/biossíntese , Adulto , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Periapicais/genética , Doenças Periapicais/imunologia , Granuloma Periapical/genética , Granuloma Periapical/imunologia , Granuloma Periapical/metabolismo , Cisto Radicular/genética , Cisto Radicular/metabolismo , Fator de Crescimento Transformador beta1/genéticaRESUMO
Stem cell factor (SCF), an important stem cell cytokine, has multiple functions. Fibroblasts (FBs), mature mast cells, endothelial cells (ECs), and eosinophil granulocytes can produce SCF in the inflammatory process. Therefore, we aimed to observe SCF expression in FBs, ECs, and macrophages (MPs) in periapical tissues in human chronic periapical disease and investigate the effects of cells expressing SCF in pathogenesis of the disease. Healthy (N = 20), periapical cyst (N = 15), and periapical granuloma (N = 15) tissues were fixed in 10% formalin for 48 h, embedded in paraffin, and stained with hematoxylin and eosin to observe histological changes. SCF expression was observed in FBs, ECs, and MPs in periapical tissues by double immunofluorescence. CD334, CD31, and CD14 are specific markers of FBs, ECs, and MPs, respectively. Results showed that densities of CD334-SCF double-positive FBs, CD31-SCF double-positive ECs, and CD14-SCF double-positive MPs were significantly increased in periapical tissue groups (P < 0.01). There were no significant differences in CD334-SCF double-positive FB and CD31-SCF double-positive EC levels between the two periapical tissue groups (P > 0.05). CD14-SCF double-positive MP density was considerably higher in periapical granulomas than in cysts (P < 0.01). FB, EC, and MP levels were significantly high and densities of CD334-SCF double-positive FBs, CD31-SCF double-positive ECs, and CD14-SCF double-positive MPs improved considerably in chronic periapical tissues, suggesting that the cells might be related to occurrence, development, and pathogenesis of chronic periapical disease.
Assuntos
Células Endoteliais/metabolismo , Fibroblastos/metabolismo , Macrófagos/metabolismo , Doenças Periapicais/metabolismo , Tecido Periapical/metabolismo , Fator de Células-Tronco/biossíntese , Adulto , Idoso , Citocinas/metabolismo , Células Endoteliais/patologia , Feminino , Fibroblastos/patologia , Humanos , Macrófagos/patologia , Masculino , Mastócitos/metabolismo , Mastócitos/patologia , Pessoa de Meia-Idade , Doenças Periapicais/patologia , Granuloma Periapical/metabolismo , Granuloma Periapical/patologia , Tecido Periapical/patologia , Cisto Radicular/metabolismo , Cisto Radicular/patologia , Fator de Células-Tronco/metabolismoRESUMO
Abstract The objective of this study was to evaluate the expression of matrix metalloproteinase 9 (MMP-9) and transforming growth factor beta (TGF-β1) in periapical lesion samples correlated with the intensity of the inflammatory infiltrate and thickness of the epithelial lining. Forty-five cases of periapical lesions (23 periapical granulomas and 22 radicular cysts) were subjected to morphological and immunohistochemical analyses using anti-MMP-9 and anti-TGF-β1 antibodies. The data were analyzed using the following tests: non-parametric Mann-Whitney, chi-square, Fisher's exact test and Spearman's correlation test (P<0.05). Analysis of inflammatory infiltrate revealed that 78% of periapical granulomas presented infiltrate grade III, in contrast with 32% of radicular cysts (P<0.001). Morphological evaluation of the epithelial thickness in radicular cysts revealed the presence of atrophic epithelium in 86% of the cysts. The immunostaining of MMP-9 was score 2 in 67% of the granulomas and 77% of the cysts. Both lesions were predominantly score 1 for TGF-β1. Significant differences were confirmed between the expression scores of TGF-β1 and MMP-9 in periapical granulomas (p = 0.004) and in radicular cysts (p < 0.001). Expression of TGF-β1 was different for periapical granulomas and radicular cysts. This immunoregulatory cytokine seems more representative in asymptomatic lesions. The extracellular matrix remodeling process dependent on MMP-9 seems to be similar for both periapical granulomas and radicular cysts. TGF-β1 and MMP-9 may play an important role in the maintenance of periapical lesions.
Assuntos
Humanos , Masculino , Feminino , Adulto , Granuloma Periapical/metabolismo , Cisto Radicular/química , Metaloproteinase 9 da Matriz/análise , Fator de Crescimento Transformador beta1/análise , Granuloma Periapical/imunologia , Granuloma Periapical/patologia , Biópsia , Índice de Gravidade de Doença , Imuno-Histoquímica/métodos , Cisto Radicular/imunologia , Cisto Radicular/patologia , Estatísticas não Paramétricas , Células Epiteliais/patologiaRESUMO
Interleukin 17A (IL-17A) is a proinflammatory cytokine responsible for the initiation and propagation of inflammation. One of its actions is the recruitment of neutrophils to the site of infection. The aim of this study was to investigate whether there is association between IL-17A expression and neutrophil infiltration in periapical abscesses and periapical granulomas, as well as to find which type of T lymphocyte effector (CD4+ or CD8+) expresses IL-17A in these lesions. Elastase, CD4, CD8, and IL-17A were analyzed by immunohistochemistry and immunofluorescence, in the biopsies of periapical lesions. Abscess lesions exhibited the highest labeling area for IL-17A (p = 0.011). During double immunofluorescence staining, there were significantly more CD4+/IL-17A+ cells compared to CD8+/IL-17A+ cells, both in the abscesses (p = 0.025) and granulomas (p = 0.011). In conclusion, IL-17A was intensively expressed in periapical abscesses rich in neutrophils. The high percentage of IL-17A in these cases suggests the participation of this cytokine particularly in the acute stages of the inflammatory process of the periapical lesions.