IDO通过整合素αvβ3调控子宫内膜间质细胞黏附能力

Modulation of IDO on adhesion ability of endometrial stromal cells through integrin αvβ3

探讨吲哚胺2,3-双加氧酶(IDO)通过细胞外黏附分子整合素对子宫内膜间质细胞(ESC)与细胞外基质黏附能力的调控。收集非内异症患者健康内膜、内异症患者在位内膜及异位内膜样组织,体外分离、培养获得子宫内膜间质细胞,并鉴定细胞纯度;In-cell Western比较分析健康、在位和异位ESC中IDO的表达水平,以及脂多糖(LPS)和1-甲基色氨酸(1-MT)单独或联合作用对IDO表达的影响;黏附试验分析LPS和(或)1-MT对ESC与细胞外基质laminin、collagen、fibrino-gen、fibronectin等黏附能力的影响;进一步应用流式细胞术分析LPS或/和1-MT对相应细胞外基质配体-整合素表达的调节。结果显示,IDO在子宫内膜异位症患者来源在位及异位ESC中高表达。炎症因子LPS可以促进ESC中IDO的表达,并通过上调整合素αvβ3增强ESC对细胞外基质collagen I、collagen IV、fibrinogen、fibronectin的黏附。IDO特异性抑制剂1-MT可以抑制ESC表达IDO,并且可以逆转LPS诱导的整合素αvβ3表达及ESC黏附能力。

To explore the regulatory effect of indoleamine 2,3-dioxygenase （IDO） on the adhesion ability of eutopic endometrialstromal cells （ESC） through integrin av133, healthy, eutopic and ectopic ESC were isolated respectively from healthy endometrium of patients without EMs, eutopic endometrium and eetopic endometriotic tissue of patients with EMs. Eutopic ESC was treated in vitro with lipopolysaceharide （LPS） and/or 1-methyl-tryptophan （1-MT）. In-cell Western blot was used to evaluate the protein expression of IDO in ESC. The modulatory effect of LPS and 1-MT alone or in combination on the adhesion ability of ESC was determined by adhesion assay, and the expression level of related integrin in ESC was detected by flow cytometric assay. It was found that IDO was highly expressed in eutopic and ectopic ESC. LPS up-regulated adhesion ability of eutopic ESC to collagen I, collagen IV, fibrinogen, fibronectin through integrin αvβ3, and IDO inhibitor-l-MT could reverse the outcome of LPS in ESC. IDO is thus proposed to improve the adhesion ability of ESC by increasing the level of integrin αvβ3