Whaley A E, Meka C S, Harbison L A, Hunt J S, Imakawa K
Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Wichita 67214-4716.
J Biol Chem. 1994 Apr 8;269(14):10864-8.
Although constitutive expression of trophoblast or pregnancy-associated interferon (IFN) has long been recognized, their cDNA sequences have been determined for only ruminant ungulates. Here we show a human trophoblast IFN (htIFN) cDNA whose nucleotide sequence is very similar (85% identity) to that of ovine and bovine trophoblast IFNs, IFN tau s. Like ruminant IFN tau s, htIFN cDNAs contain an open reading frame of 195 codons including a signal sequence of 23 amino acids, resulting in a mature polypeptide of 172 amino acids. The deduced amino acid sequence of htIFN shares 73, 62, and 56% identities with ovine IFN tau, human IFN alpha II, and human IFN alpha I, respectively. However, the expression of htIFN is not limited to a specific period of pregnancy because transcripts of htIFN genes are detected in human lymphocytes, cells obtained by amniocentesis (amniocytes), first trimester, and term placentas. Human trophoblast IFN mRNA is localized mainly in extravillous trophoblasts cells of placental villi, particularly in the migrating cytotrophoblasts cells, which eventually replace maternal endothelial cells in spiral arteries of the decidua. Both sense and antisense mRNAs for human IFN alpha II are localized in the outer layer of villous structures. Coexistence of these mRNAs at the placental villi throughout pregnancy suggests that, in addition to a role in placental cell growth and differentiation, IFNs may play a role protecting the fetus in viral environments.
尽管滋养层或妊娠相关干扰素(IFN)的组成性表达早已为人所知,但仅反刍有蹄类动物的其cDNA序列已被确定。在此,我们展示了一种人滋养层干扰素(htIFN)cDNA,其核苷酸序列与绵羊和牛的滋养层干扰素IFN tau的序列非常相似(85% 同源性)。与反刍动物的IFN tau一样,htIFN cDNA包含一个由195个密码子组成的开放阅读框,其中包括一个23个氨基酸的信号序列,产生一个由172个氨基酸组成的成熟多肽。htIFN推导的氨基酸序列与绵羊IFN tau、人IFNα II和人IFNα I的同源性分别为73%、62%和56%。然而,htIFN的表达并不局限于妊娠的特定时期,因为在人淋巴细胞、羊膜穿刺术获得的细胞(羊膜细胞)、孕早期和足月胎盘组织中都检测到了htIFN基因的转录本。人滋养层干扰素mRNA主要定位于胎盘绒毛的绒毛外滋养层细胞,特别是迁移的细胞滋养层细胞,这些细胞最终取代蜕膜螺旋动脉中的母体内皮细胞。人IFNα II的正义和反义mRNA都定位于绒毛结构的外层。在整个妊娠期间这些mRNA在胎盘绒毛处共存表明,IFN除了在胎盘细胞生长和分化中起作用外,可能在病毒环境中对胎儿起到保护作用。