MicroR-146 blocks the activation of M1 macrophage by targeting signal transducer and activator of transcription 1 in hepatic schistosomiasis

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• 作者：Xing He^a ; ¹ ; Rui Tang^a ; ^b ; ¹ ; Yue Sun^a ; ^b ; Yan-Ge Wang^a ; Kui-Yang Zhen^a ; Dong-Mei Zhang^a ; ^{dmzhangcn@163.com} ; Wei-Qing Pan^a ; ^{wqpan0912@aliyun.com}
• 关键词：miR-146 ; macrophage differentiation ; hepatic schistosomiasis ; STAT pathway
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：13
• 期：Complete
• 页码：339-347
• 全文大小：1074 K
• 卷排序：13

文摘

miR-146 was selectively upregulated in macrophages during hepatic schistosomiasis.miR-146 blocked the differentiation of macrophages into M1 cells by targeting STAT1 in hepatic schistosomiasis.Th2 cytokines induced the expression of miR-146b by activating STAT3/6 that bind to the promoter of the pre-miR-146b gene.Th2 cytokines inhibited the activation of M1 macrophages by induction of miR-146b.Macrophages play a central role in schistosomiasis by differentiating into various activation states. Previous studies have highlighted the importance of differentiation of macrophages into M2 cells for host survival. In this study, we revealed that the presence of liver-trapped parasite eggs induced expression of Th2 cytokines that promoted transcription of miR-146b by activating STAT3/6 that bind to the promoter of the pre-miR-146b gene, and the elevated miR-146b inhibited the IFN-γ-induced differentiation of macrophages into M1 cells by suppressing STAT1. These findings indicate the protective roles of miR-146a/b in hepatic schistosomiasis through regulating the differentiation of macrophages into M2 cells.