Sun Xiao-Hua, Fu Jia, Sun Da-Qing
Department of Emergency, Xi'an Children's Hospital, Xi'an, 710003, Shanxi, PR China.
Department of Infection, Xi'an Children's Hospital, Xi'an, 710003, Shanxi, PR China.
Biochem Biophys Res Commun. 2016 Apr 29;473(2):558-64. doi: 10.1016/j.bbrc.2016.03.118. Epub 2016 Mar 25.
Viral myocarditis (VMC) is an inflammation of heart muscle in infants and young adolescents. This study explored the function of halofuginone (HF) in Coxsackievirus B3 (CVB3) -treated suckling mice. HF-treated animal exhibited higher survival rate, lower heart/body weight, and more decreased blood sugar concentration than CVB3 group. HF also reduced the expressions of interleukin(IL)-17 and IL-23 and the numbers of Th17 cells. Moreover, HF downregulated pro-inflammatory cytokine levels and increased anti-inflammatory cytokine levels. The expressions of transforming growth factor(TGF-β1) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) p65/ tumor necrosis factor-α (TNF-α) proteins were decreased by HF as well. Finally, the overexpression of TGF-β1 counteracted the protection effect of HF in CVB3-treated suckling mice. In summary, our study suggests HF increases the survival of CVB3 suckling mice, reduces the Th17 cells and pro-inflammatory cytokine levels, and may through downregulation of the TGF-β1-mediated expression of NF-κB p65/TNF-α pathway proteins. These results offer a potential therapeutic strategy for the treatment of VMC.
病毒性心肌炎（VMC）是婴幼儿和青少年心肌的一种炎症。本研究探讨了常山酮（HF）在柯萨奇病毒B3（CVB3）感染的乳鼠中的作用。与CVB3组相比，HF治疗的动物存活率更高，心脏/体重更低，血糖浓度下降更多。HF还降低了白细胞介素（IL）-17和IL-23的表达以及Th17细胞的数量。此外，HF下调促炎细胞因子水平并增加抗炎细胞因子水平。HF还降低了转化生长因子（TGF-β1）和活化B细胞核因子κB轻链增强子（NF-κB）p65/肿瘤坏死因子-α（TNF-α）蛋白的表达。最后，TGF-β1的过表达抵消了HF对CVB3感染乳鼠的保护作用。总之，我们的研究表明HF提高了CVB3感染乳鼠的存活率，降低了Th17细胞和促炎细胞因子水平，并且可能通过下调TGF-β1介导的NF-κB p65/TNF-α通路蛋白的表达来实现。这些结果为VMC的治疗提供了一种潜在的治疗策略。
