Interferon Tau Regulates Cytokine Production and Cellular Function in Human Trophoblast Cell Line
Interferon Tau Regulates Cytokine Production and Cellular Function in Human Trophoblast Cell Line
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DOI：
10.1089/jir.2017.0057
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发表时间：
2017-10-01
影响因子：
2.3
通讯作者：
Shirasuna, Koumei
中科院分区：
文献类型：
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作者：
Tanikawa, Nao;Seno, Kotomi;Shirasuna, Koumei
I型干扰素（IFN），包括IFN-β（IFNB），激活多种STAT信号传导以驱动各种生物学应答。另一种I型IFN，IFN-tau（IFNT），由反刍动物胚胎滋养层细胞分泌，具有多种功能和低细胞毒性。在这里，我们研究了IFNT对人类滋养层细胞功能的影响。首先，我们进行了下一代测序，并证明了IFNT依赖的变化在人类SW。71滋养层细胞系部分介导的促炎以及IFN信号。接下来，我们验证了候选基因，数据证实IFNT刺激白细胞介素-6（IL-6）和IL-8 mRNA的表达和分泌。然而，人IFNB不影响IL-6和IL-8 mRNA的表达和分泌。IFN诱导的细胞因子分泌依赖于STAT 3信号，而不是STAT 1信号。此外，用IFNT、IL-6或IL-8处理增加细胞增殖，并且IFNT还刺激人滋养层细胞中的细胞迁移。虽然IFNT不影响超氧化物歧化酶（SOD）1 mRNA的表达，但它明显增加线粒体SOD 2 mRNA的表达，导致SOD活性的加速。我们证明，除了IFN信号，IFNT也调节炎症相关的信号，以及细胞增殖，迁移，和氧化还原信号在人类滋养层细胞。
Type I interferons (IFN), including IFN-beta (IFNB), activate multiple STAT signaling to drive various biological responses. Another type I IFN, IFN-tau (IFNT), secreted by ruminant embryonic trophoblast cells, has multiple functions with low cytotoxicity. Here, we examined the effects of IFNT on human trophoblast cell functions. First, we performed next-generation sequencing and demonstrated that IFNT-dependent changes in the human Sw.71 trophoblast cell line are partly mediated by proinflammatory as well as IFN signaling. Next, we validated candidate genes, and data confirmed that IFNT stimulated interleukin-6 (IL-6) and IL-8 mRNA expression and secretion. However, human IFNB did not affect IL-6 and IL-8 mRNA expression and secretion. IFNT-induced cytokine secretion was dependent on STAT3 signaling, but not STAT1 signaling. In addition, treatment with IFNT, IL-6, or IL-8 increased cell proliferation, and IFNT also stimulated cell migration in human trophoblast cells. Although IFNT did not affect superoxide dismutase (SOD) 1 mRNA expression, it clearly increased mitochondrial SOD2 mRNA expression, resulting in the acceleration of SOD activity. We demonstrated that in addition to IFN signaling, IFNT also regulated inflammation-related signaling as well as cell proliferation, migration, and redox signaling in human trophoblast cells.