Inhibition of IDO1 suppresses cyclooxygenase-2 and matrix metalloproteinase-9 expression and decreases proliferation, adhesion and invasion of endometrial stromal cells
Inhibition of IDO1 suppresses cyclooxygenase-2 and matrix metalloproteinase-9 expression and decreases proliferation, adhesion and invasion of endometrial stromal cells
复制标题
抑制 IDO1 可抑制环氧合酶 2 和基质金属蛋白酶 9 的表达，并减少子宫内膜基质细胞的增殖、粘附和侵袭
DOI：
10.1093/molehr/gas021
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发表时间：
2012-10-01
影响因子：
4
通讯作者：
Zhu, Xiao-Yong
中科院分区：
文献类型：
--
作者：
Mei, Jie;Jin, Li-Ping;Zhu, Xiao-Yong
吲哚胺2，3-双加氧酶-1（IDO 1）是一种细胞内酶，可沿着犬尿氨酸途径催化必需氨基酸色氨酸。本研究旨在探讨IDO 1表达对子宫内膜间质细胞（ESCs）生物学特性的影响。采用细胞内免疫印迹法检测异位基质细胞、异位源性在位基质细胞和正常ESCs（对照）中IDO 1、环氧合酶考克斯2和基质金属蛋白酶（MMPs）的表达。在用脂多糖、左旋-1-甲基-色氨酸（L-1-MT）单独或组合处理后，评价上述蛋白质表达的比较分析。分别采用ELISA法、黏附实验和Matrigel侵袭实验检测IDO 1对ESCs增殖、黏附和侵袭的影响。结果显示，与来自对照妇女的健康ESC相反，IDO 1在来自子宫内膜异位症妇女的在位和异位ESC中的表达显著更高。L-1-MT抑制IDO 1可抑制考克斯-2和MMP-9的表达。它还可以减少ESCs的增殖、粘附和侵袭，同时刺激ESCs的脱落。IDO 1可能通过促进考克斯-2和MMP-9的表达，调节ESCs的生物学特性，参与子宫内膜异位症的发病过程。这些信息可能有助于开发新的治疗策略子宫内膜异位症。
Indoleamine 2,3-dioxygenase-1 (IDO1) is an intracellular enzyme that catalyses essential amino acid tryptophan along the kynurenine pathway. The aim of this study was to determine the impact of IDO1 expression on the biological characteristic of the endometrial stromal cells (ESCs). IDO1, cyclooxygenase-2 (COX-2) and matrix metalloproteinases (MMPs) in endometriotic ectopic stromal cells, endometriosis-derived eutopic stromal cells and normal ESCs (control) were detected by the in-cell Western analysis. After being treated with lipopolysaccharide, levo-1-methyl-tryptophan (L-1-MT) alone or a combination, a comparative analysis of the above protein expression was evaluated. The effects of IDO1 on ESCs proliferation, adhesion and invasion were detected through ELISA, adhesion assay and Matrigel invasion assay, respectively. The results showed that, contrary to healthy ESCs from control women, the expression of IDO1 was significantly higher in eutopic and ectopic ESCs obtained from women with endometriosis. Inhibition of IDO1 by L-1-MT suppressed the expression of COX-2 and MMP-9 in ESCs. It could also decrease the ESCs proliferation, adhesion and invasion, while stimulating ESCs decidualization. Thus, IDO1 is possibly involved in endometriosis pathogenesis via promoting COX-2 and MMP-9 expression and regulation of ESCs biological characteristics. The information may be useful for developing a new therapeutic strategy for endometriosis.