Kudo Yoshiki, Koh Iemasa, Sugimoto Jun
Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Int J Tryptophan Res. 2020 Dec 28;13:1178646920984163. doi: 10.1177/1178646920984163. eCollection 2020.
Immunohistochemical localization of indoleamine 2,3-dioxygenase-1 and indoleamine 2,3-dioxygenase-2, the first and rate-limiting enzyme in tryptophan metabolism along the kynurenine pathway, has been studied in order to better understand the physiological significance of these enzymes at the maternal-fetal interface of human pregnancy with a gestational age of 7 weeks (n = 1) and term placentas (37-40 weeks of gestation, n = 5). Indoleamine 2,3-dioxygenase-1 protein immunoreactivity was found in glandular epithelium of the decidua and the endothelium of the fetal blood vessels in the villous stroma with some additional positive cells in the villous core and in the decidua. The syncytiotrophoblast stained strongly for indoleamine 2,3-dioxygenase-2. Immunoreactivity of kynurenine, the immediate downstream product of indoleamine 2,3-dioxygenase-mediated tryptophan metabolism, showed the same localization as that of indoleamine 2,3-dioxygenase-1 and indoleamine 2,3-dioxygenase-2, suggesting these are functional enzymes. Interferon-γ added to placental villous explant culture markedly stimulated expression level of both mRNA and immunoreactivity of indoleamine 2,3-dioxygenase-1. The different cellular expression and interferon-γ sensitivity of these enzymes at the maternal-fetal interface suggests distinct physiological roles for each enzyme in normal human viviparity.
为了更好地理解吲哚胺2,3-双加氧酶-1（IDO-1）和吲哚胺2,3-双加氧酶-2（IDO-2）这两种色氨酸沿犬尿氨酸途径代谢的首个且限速酶在人类妊娠母胎界面的生理意义，研究人员对孕龄7周（n = 1）的人类妊娠母胎界面以及足月胎盘（妊娠37 - 40周，n = 5）进行了免疫组化定位研究。在蜕膜的腺上皮和绒毛间质中胎儿血管的内皮中发现了吲哚胺2,3-双加氧酶-1蛋白免疫反应性，在绒毛核心和蜕膜中还有一些额外的阳性细胞。合体滋养层对吲哚胺2,3-双加氧酶-2染色强烈。吲哚胺2,3-双加氧酶介导的色氨酸代谢的直接下游产物犬尿氨酸的免疫反应性显示出与吲哚胺2,3-双加氧酶-1和吲哚胺2,3-双加氧酶-2相同的定位，表明这些是功能性酶。添加到胎盘绒毛外植体培养物中的干扰素-γ显著刺激了吲哚胺2,3-双加氧酶-1的mRNA表达水平和免疫反应性。这些酶在母胎界面的不同细胞表达和对干扰素-γ的敏感性表明每种酶在正常人类胎生过程中具有不同的生理作用。
