Constitutive and trophoblast-specific expression of a class of bovine interferon genes.

Constitutive and trophoblast-specific expression of a class of bovine interferon genes.
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一类牛干扰素基因的组成型和滋养层特异性表达。

DOI:
10.1073/pnas.88.9.3817
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发表时间:
1991
影响因子:
11.1
通讯作者:
Roberts,RM
Roberts,RM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cross,JC;Roberts,RM

文献摘要

被引文献

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绵羊和牛的早期胚胎分泌一种称为绵羊和牛滋养层蛋白1(TP-1)的低分子量蛋白质,该蛋白质对于建立妊娠至关重要。TP-1是一种I型干扰素(IFN),与IFN-ω最相关。在这里,我们已经确定,如果TP-1基因的调节类似于其他I型干扰素。在培养物中,第18天的牛孕体每小时分泌约10(5)单位的IFN抗病毒活性,比仙台病毒诱导的白细胞产生的量高约300倍。虽然孕体表达IFN-α、IFN-ω和TP-1的mRNA,但TP-1占所产生IFN的99%以上。相比之下,白细胞主要产生IFN-α,尽管TP-1 mRNA可被仙台病毒诱导至非常低的水平。通过北方分析,TP-1 mRNA在妊娠早期的孕体中可检测到,但在妊娠晚期的胎盘和几种成人组织中不存在。转染的牛TP-1基因在不存在任何特异性刺激的情况下在人绒毛膜癌(CHCM)细胞中表达,而这些细胞组成性地或在用牛IFN-ω基因转染后不分泌抗病毒活性。然而,转染的TP-1基因在非滋养层细胞(小鼠L929和仓鼠中国仓鼠卵巢)中不表达。TP-1基因的5 ′启动子区足以在哺乳动物细胞中将滋养层特异性表达引导到人生长激素报告基因上。启动子从-450至-126的缺失导致表达降低4至5倍。总之,这些数据表明,TP-1的基因是可诱导的病毒,但优先在滋养层细胞中表达,并在功能上不同于IFN-ω基因。
The early conceptus in sheep and cattle secretes a low molecular weight protein called ovine and bovine trophoblast protein 1 (TP-1) that is critical for establishment of pregnancy. TP-1 is a type I interferon (IFN) and is most related to IFN-omega. Here we have determined if TP-1 genes are regulated similarly to other type I IFNs. Single day 18 bovine conceptuses secrete approximately 10(5) units of IFN antiviral activity per hour in culture, amounts approximately 300 times higher than those produced by Sendai virus-induced leukocytes. Although conceptuses express mRNA for IFN-alpha, IFN-omega, and TP-1, TP-1 constitutes greater than 99% of the IFN produced. In contrast, leukocytes produced predominantly IFN-alpha, although TP-1 mRNA is inducible by Sendai virus to very low levels. TP-1 mRNA is detectable by Northern analysis in conceptuses from early pregnancy but is absent in late gestation placenta and several adult tissues. Transfected bovine TP-1 genes are expressed in human choriocarcinoma (JAR) cells in the absence of any specific stimulus, whereas these cells do not secrete antiviral activity constitutively or after transfection with a bovine IFN-omega gene. The transfected TP-1 gene is not expressed in nontrophoblast cells (mouse L929 and hamster Chinese hamster ovary), however. The 5' promoter region of the TP-1 gene is sufficient to direct trophoblast-specific expression onto a human growth hormone reporter gene in JAR cells. Deletion of the promoter from -450 to -126 results in a 4- to 5-fold decrease in expression. Together these data demonstrate that the genes for TP-1 are inducible by virus but are expressed preferentially in trophoblast cells and are functionally distinct from IFN-omega genes.