Effects of emodin on IL-23/IL-17 inflammatory axis, Th17 cells and viral replication in mice with viral myocarditis / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effects of emodin in myocardial protection in mice with viral myocarditis (VMC) and explore molecular mechanisms.</p><p><b>METHODS</b>Fifty-five male 4-week-old BALB/c mice were randomly divided into control group (n=15), model group (n=20), and emodin group (n=20). The mice in model and emodin groups were inoculated with 0.1 ml Eagle's solution containing coxsackievirus B3 intraperitoneally, and those in the control group were given only 0.1 ml Eagle's solution. From the day of inoculation, the mice in emodin group received intragastric administration with 0.1 ml of 3 mg/ml emodin solution once daily for 21 consecutive days, and those in the control and model groups received 0.1 ml distilled water only. On day 7 after inoculation, 5 mice from each group were sacrificed to determine the viral titers in the cardiac tissues. All the mice were sacrificed on day 22 for measurement of the heart weight and histopathological inspection of the heart with HE staining. The mRNA and protein expression levels of myocardial interleukin-23 (IL-23) and interleukin-17 (IL-17) were detected by real-time quantitative PCR and Western blotting, respectively, and serum IL-23 and IL-17 levels were examined using enzyme linked immunosorbent assay (ELISA). Th17 cell frequencies were analyzed by flow cytometry. The expression levels of myocardial nuclear factor-κB (NF-κB) p65 in the cardiomyocyte nuclei were examined using Western blotting, and myocardial interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) contents were detected by ELISA.</p><p><b>RESULTS</b>The mortality, myocardial histopathologic scores and virus titers in emodin group were all significantly lower than those in the model group (P<0.05). The heart-to-body weight ratio, myocardial IL-23 and IL-17 expressions, serum IL-23 and IL-17 levels, Th17 cell frequencies, cardiomyocyte nuclear NF-κB p65 expression, and myocardial contents of IL-1β, IL-6 and TNF-α were all significantly increased in the model group as compared to the control group (P<0.01) but reduced significantly in emodin group as compared to model group (P<0.05).</p><p><b>CONCLUSION</b>Emodin can protect against VMC by inhibiting IL-23/IL-17 inflammatory axis, Th17 cell proliferation and viral replication in mice.</p>