Assuntos
Fibrilação Atrial , Anticoagulantes , Aspirina , Humanos , Inibidores da Agregação PlaquetáriaAssuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Feminino , Humanos , Masculino , Stents , Resultado do TratamentoRESUMO
BACKGROUND: The IL-23/Th17 pathway is implicated in the pathogenesis of a number of chronic inflammatory and autoimmune diseases. Whether it regulates the viral myocarditis (VMC) is unknown. RESULTS: To examine the pathogenesis role of IL-23/Th17 axis in VMC, we used male BALB/c mice to induced VMC by Coxsackie virus B3 (CVB3) peritoneal injection. IL-23, IL-17, and signal transducer and activator of transcription 3 (STAT3) mRNA in the myocardium of VMC mice were assessed by semi-quantitative RT-PCR. IL-23 and IL-17 protein from blood serum were evaluated by ELISA. Phosphorylated-STAT3 (p-STAT3) protein expression in the myocardium was evaluated by immunohistochemical staining. Flow cytometric analysis was used to evaluate the frequencies of Th17 subsets. Isolated CD4+ T cells from VMC mice were cultured with recombinant IL-23(rIL-23) in vitro. In addition, a STAT3-specific inhibitor (S3I-201) was used to test whether regulation of STAT3 could be partly responsible for Th17 diminution. Results showed that expression of IL-23, IL-17, STAT3 mRNA and protein increased in VMC mice. When purified CD4+ T cells derived from VMC mice were cultured in vitro with rIL-23, the frequency of Th17 cells was dramatically increased, accompanied by significantly enhanced production of IL-17 in the supernatants of cultured CD4+ T cells. S3I-201 significantly restrained Th17 cell proliferation. CONCLUSIONS: The IL-23/Th17 pathway axis is strongly expressed in murine VMC, identifying a novel pathway of potential significance in viral myocarditis.
Assuntos
Infecções por Coxsackievirus/patologia , Enterovirus/patogenicidade , Interleucina-17/imunologia , Interleucina-23/imunologia , Miocardite/patologia , Animais , Linfócitos T CD4-Positivos/imunologia , Infecções por Coxsackievirus/imunologia , Enterovirus/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Perfilação da Expressão Gênica , Imuno-Histoquímica , Interleucina-17/sangue , Interleucina-17/genética , Interleucina-23/sangue , Interleucina-23/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Miocardite/imunologia , Miocárdio/patologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Células Th17/imunologiaRESUMO
OBJECTIVE: To observe the alteration of interleukin-17 and interferon-γ double positive cells (IL-17(+)/IFN-γ(+) cells) in mice with coxsackie virus B3 (CVB3) induced acute viral myocarditis (VMC). METHODS: VMC was induced in male Balb/c mice by peritoneal injection of CVB3. Control mice received PBS injection. At 0, 1, 2, 3, 4 and 6 weeks after injection, pathological scores were determined on hematoxylin-eosin stained heart sections and flow cytometric analysis was performed to evaluate the percent of IL-17(+)/IFN-γ(+) cells among CD4(+) T cells. RESULTS: Compared to control mice, the pathological scores of VMC mice were higher on CVB3 infection week 1 (1.8 ± 0.5), peaked on week 2 (2.8 ± 0.5) and declined thereafter. However, the proportion of IL-17(+)/IFN-γ(+) cells remained steadily at a low level throughout the observation period and was similar between VMC and control mice. CONCLUSIONS: Our data shows that IL-17(+)/IFN-γ(+) cells might not be involved in the inflammation process of CVB3 induced VMC mice model.
