ABSTRACT
Objective: This study aimed to investigate whether interleukin-28A (IL-28A) plays a role in murine myocarditis induced by coxsackievirus B3 (CVB3), and to explore its possible mechanism involved. Methods: Male BALB/c mice both infected and not infected by CVB3 were randomly divided into four groups (n = 40), untreated or treated with different doses of IL-28A for 4 days, and then sacrificed on days 4 and 7 post-infection. The heart samples were collected for histopathologic examination. Cardiac viral load was determined by a plaque assay. Additionally, immunoblot analysis, TUNEL assay, and immunohistochemistry were performed to examine the expression of signal transducer, activator of transcription 1 and 2 (STAT1 and STAT2), CVB3-induced apoptosis and the expression of Bcl-2, BAX and Caspase-3. Results: Compared to uninfected mice, the CVB3 infected mice exhibited higher mortality rate (p < 0.001), apparent inflammation and myocardial lesion (p < 0.01), and higher cardiac viral load (p < 0.01). After CVB3 infection, IL-28A treated mice presented no death (p < 0.001), reduced inflammation and myocardial lesion (p < 0.01), and lower viral load (p < 0.01) compared to untreated mice. Besides, treatment with IL-28A markedly increased the expressions of STAT1 and STAT2, and inhibited CVB3-induced apoptosis in myocardial cells with increased ratio of Bcl-2/BAX. Conclusion: The antiviral and myocyte protective effects of IL-28A in CVB3-inducedmyocarditis are regulated by STAT1 and STAT2. .
Subject(s)
Animals , Male , Mice , Antiviral Agents/therapeutic use , Coxsackievirus Infections , Interleukins/metabolism , Myocarditis/virology , Apoptosis , /immunology , /metabolism , Coxsackievirus Infections/drug therapy , Coxsackievirus Infections/immunology , Coxsackievirus Infections/metabolism , Immunoblotting , Immunohistochemistry , In Situ Nick-End Labeling , Interleukins/immunology , Mice, Inbred BALB C , Myocarditis/immunology , Myocarditis/metabolism , /immunology , /metabolism , STAT1 Transcription Factor/immunology , STAT1 Transcription Factor/metabolism , /immunology , /metabolism , Viral Load , /immunology , /metabolismABSTRACT
The intercellular adhesion molecule is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Serum and cerebrospinal fluid (CSF) soluble intercellular adhesion molecule 1 (sICAM-1) from normal control children as well as from children with Guillain-Barré syndrome (GBS), with Coxsackie A9 virus meningoencephalitis and with Streptococcus pneumoniae meningoencephalitis were studied. sICAM-1 was quantified using an immunoenzimatic assay and albumin using the immunodiffusion technique in both biological fluids. Increased sICAM-1 values in CSF in patients with GBS correspond to an increase of the albumin CSF/serum quotient. In contrast, in inflammatory diseases like S. pneumoniae and Coxsackie A9 virus meningoencephalitis an increased brain-derived fraction was observed. In particular cases these values are 60-65 percent and 70-75 percent respectively. The results indicate an additional synthesis of sICAM-1 in subarachnoidal space during central nervous system (CNS) inflammatory process. An important role of sICAM-1 in the transmigration of different cell types into CSF during CNS inflammation in children with S. pneumoniae and Coxsackie A9 meningoencephalitis may be suggested.
La molécula de adhesión intercelular es una glicoproteína que pertenece a la superfamilia de las inmunoglobulinas. Se estudiaron los niveles de molécula de adhesión intercelular tipo 1 soluble (sICAM-1) en suero y líquido cefalorraquídeo (LCR) de niños con meningoencefalitis por Streptococcus pneumoniae y por Coxsackie A9 al igual que en niños con sindrome de Guillain-Barré (SGB). sICAM-1 fue cuantificado por ensayo inmunoenzimático y la albúmina por inmunodifusión en ambos líquidos biológicos. Los valores incrementados de sICAM-1 en LCR en los pacientes con GBS corresponden a valores aumentados de razón LCR/suero de albúmina. En contraste, en las enfermedades inflamatorias como las meningoencefalitis por S. pneumoniae y por Coxsackie A9 se observa un incremento en la fracción derivada del cerebro. En casos particulares los valores se incrementan hasta un 60-65 por ciento y 70-75 por ciento respectivamente. Los resultados indican una síntesis adicional de sICAM-1 en el espacio subaracnoideo durante el proceso inflamatorio del sistema nervioso central (SNC). Esto puede sugerir un importante papel del sICAM-1 en la transmigración de diferentes tipos celulares en el LCR durante la inflamación del SNC en niños con meningoencefalitis por S pneumoniae y coxsackie A9.