RESUMO
Oral lichen planus (OLP) is a common T cell-mediated chronic inflammatory disease of unknown etiology. Recent increasing evidence indicates that microRNA-146a (miR-146a) plays a vital role in inflammatory diseases and T cell regulation. This study aimed to investigate the expression of miRNA-146a in peripheral blood CD4(+) T cells and local OLP lesions and to evaluate its relationship with clinical forms of OLP. Sixteen patients with OLP were divided into two groups: erosive OLP and nonerosive OLP. The expression of miR-146a was examined by quantitative real-time polymerase chain reaction. The expression of miR-146a in peripheral blood CD4(+) T cells showed no significant difference between OLP group and control group (P > 0.05), and among erosive OLP, nonerosive OLP, and control groups (P > 0.05 for all). The expression in local lesions of the OLP group was significantly higher than that of the control group (P = 0.003), and it was significantly higher in the erosive OLP group than in the non-erosive OLP (P = 0.010) and control groups (P = 0.007). However, miR-146a expression in the nonerosive OLP group did not significantly differ from that in the control group (P > 0.05). These data indicate that miR-146a might be more involved in the local immune disorder of OLP. MiR-146a might be utilized as a candidate biomarker to estimate the severity of OLP.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Líquen Plano Bucal/imunologia , MicroRNAs/genética , Adulto , Feminino , Marcadores Genéticos/genética , Humanos , Líquen Plano Bucal/patologia , Masculino , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Adulto JovemRESUMO
Oral lichen planus (OLP) is a T cell-mediated immune disorder, and we have indicated a Th1-dominated immune response in OLP. MicroRNA-155 (miR-155) could promote Th1 cells polarization. The present study aims to determine the role of miR-155 in immune response of OLP. The expression of miR-155 and the target mRNA was tested by Real-Time PCR. The serum levels of IL-2, 4, 10 and IFN-γ were examined with ELISA. Furthermore, in vitro study was built to observe the function of miR-155 in erosive-type OLP (EOLP). Finally, we determined the expression and correlation of miR-155 and SOCS1 in EOLP CD4(+) T cells. The results showed miR-155 was high related with the disease severities. Besides, serum IFN-γ was specifically increased in EOLP group, while IL-4 was decreased. In vitro studies showed miR-155 could reinforce IFN-γ signal transducer, and the induction of IFN-γ could also promote miR-155 expression in EOLP CD4(+) T cells. In addition, miR-155 levels were negatively related with SOCS1 mRNA expression in EOLP CD4(+) T cells. Our study revealed a positive miR-155- IFN-γ feedback loop in EOLP CD4(+) T cell, which might contribute to the Th1-dominated immune response. Furthermore, miR-155 could be used for the evaluation and treatment of OLP.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Retroalimentação Fisiológica , Interferon gama/genética , Líquen Plano Bucal/genética , MicroRNAs/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Adulto , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/patologia , Estudos de Casos e Controles , Diferenciação Celular , Proliferação de Células , Feminino , Regulação da Expressão Gênica , Humanos , Interferon gama/imunologia , Interferon gama/farmacologia , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-2/genética , Interleucina-2/imunologia , Líquen Plano Bucal/classificação , Líquen Plano Bucal/imunologia , Líquen Plano Bucal/patologia , Masculino , MicroRNAs/imunologia , Pessoa de Meia-Idade , Cultura Primária de Células , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Índice de Gravidade de Doença , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/imunologiaRESUMO
PURPOSE: To investigate the miRNA (including miR-155, miR-146a and miR-146b) expression in peripheral blood mononuclear cells (PBNCs) or lesions tissues in oral lichen planus (OLP) patients and healthy controls and the relationship between miRNA and OLP clinical features. METHODS: The expression of miRNAï¼miR-155, miR-146a and miR-146bï¼was assessed by quantitative fluorescent PCR in peripheral blood cells or lesions tissues in OLP patients and healthy controls. U6 was used as reference gene. Statistical analysis was performed with SPSS17.0 software package. RESULTS: Real-time PCR showed that the expression of miR-155 in OLP PBNCs was significantly higher than that in controls, miR-155 expression in OLP lesions tissues was 7.0 times higher than that of PBMCs. Correlation analysis showed that the level of miR-155 expression in PBMCs was positively correlated with REU score(correlation coefficient R=0.887, P<0.01). There was no significant difference in miR-146a and miR-146b expression in PBMCs between OLP and control group. On the contrary, the miR-146a expression in OLP lesions tissues was significantly upreguated than that in control group (P=0.003). CONCLUSIONS: The results indicated that miR-155 and miR-146a might play important roles in the pathogenesis of OLP and OLP is likely a chronic inflammatory disease characterized by local inflammation.
Assuntos
Leucócitos Mononucleares/metabolismo , Líquen Plano Bucal/metabolismo , MicroRNAs/metabolismo , Humanos , Inflamação , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Oral lichen planus (OLP) is a T cell-mediated autoimmune disease of oral mucosa, in which T helper 1 (Th1) cells are greatly involved. Chemokine CCL5 is required for T cells infiltration and activation. CCR5, one of its receptors, specifically expressed on Th1 cells among CD4(+) T cells, can be up-regulated by Th1 cytokines like interleukin2 (IL-2) and interferon-gamma (IFN-γ), and down-regulated by Th2 cytokines like IL-4. The present study aimed to determine whether CCL5 and CCR5 had effects on the immune response of OLP. We analyzed the proportion of CCR5(+)CD4(+) T cells in CD4(+) T cells using flow cytometry and the serum levels of CCL5, IL-2, IFN-γ, and IL-4 with ELISA. MicroRNA-125a (miR-125a), a blocker of CCL5, was examined with RT-PCR. The results showed both the serum CCL5 and the percentage of CCR5(+)CD4(+) T cells elevated in OLP patients. Serum IL-2 and IFN-γ increased in OLP patients, but IL-4 decreased. MiR-125a was down-regulated in OLP patients, and there was a negative correlation between miR-125a content and the OLP severity which was measured with a RAE (reticular, atrophic and erosive lesion) scoring system. In conclusion, increasing CCl5/CCR5 might participate in the immune response of OLP. Th1-type cytokines environment presented in OLP probably performed as a magnifier for the CCR5. Moreover, miR-125a might be a candidate biomarker to estimate the severity of OLP.