The expression and possible roles of chemokine CXCL11 and its receptor CXCR3 in the human endometrium
The expression and possible roles of chemokine CXCL11 and its receptor CXCR3 in the human endometrium
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DOI：
10.4049/jimmunol.177.12.8813
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发表时间：
2006-12-15
影响因子：
4.4
通讯作者：
Taketani, Yuji
中科院分区：
文献类型：
--
作者：
Hirota, Yasushi;Osuga, Yutaka;Taketani, Yuji
ifn - γ由人胚胎和滋养细胞在着床过程中分泌，在着床和妊娠中发挥重要作用。在本研究中，我们探讨了ifn - γ强烈诱导的CXC趋化因子CXCL11及其受体CXCR3在人子宫内膜中的表达及其可能的功能。体外培养的子宫内膜基质细胞（ESC）中未检测到分泌的CXCL11蛋白，但在体外培养的子宫内膜上皮细胞（EEC）中检测到。ifn - γ在EEC和ESC中以剂量依赖的方式刺激CXCL11蛋白水平。100 ng/ml IFN-gamma作用下EEC分泌的CXCL11是对照组的220倍，是相同剂量IFN-gamma作用下ESC分泌的100倍。CXCR3在EEC、ESC和滋养细胞中表达。在EEC中添加ifn - γ可提高其培养基对滋养细胞和T细胞的趋化活性，但该作用可通过三种CXCR3配体（包括抗CXCL11抗体）的抗体免疫中和抑制。CXCL11可显著增加ESC的BrdU掺入，而这种掺入可被p42/44 MAPK通路抑制剂PD98059抑制。相比之下，CXCL11显著降低BrdU掺入，增加乳酸脱氢酶的释放和膜联蛋白V在EEC中的阳性染色。这些发现表明ifn - γ通过刺激EEC产生CXCL11促进着床，CXCL11诱导滋养层细胞和T细胞迁移、ESC增殖和EEC凋亡。
IFN-gamma secreted by a human embryo and trophoblast cells during implantation is suggested to play an important role in implantation and pregnancy. In the present study, we explored expression and possible functions of CXCL11, a CXC chemokine strongly induced by IFN-gamma, and its receptor CXCR3 in the human endometrium. Secreted CXCL11 protein was not detected in cultured endometrial stromal cells (ESC) but was detected in cultured endometrial epithelial cells (EEC). IFN-gamma stimulated the protein levels of CXCL11 in a dose-dependent manner in EEC and ESC. CXCL11 secreted from EEC with 100 ng/ml IFN-gamma was 220-fold of the control, and 100-fold as compared with that secreted from ESC with the same dose of IFN-gamma. CXCR3 was expressed in EEC, ESC, and trophoblast cells. Addition of IFN-gamma to EEC increased the chemotactic activity of its culture medium to trophoblast cells and T cells, and the effect was suppressed by immunoneutralization with Abs of three CXCR3 ligands, including anti-CXCL11 Ab. CXCL11 significantly increased BrdU incorporation of ESC, which was inhibited by a p42/44 MAPK pathway inhibitor PD98059. In contrast, CXCL11 significantly decreased BrdU incorporation and increased the release of lactate dehydrogenase and the positive staining of annexin V in EEC. These findings suggest that IFN-gamma promotes implantation by stimulating EEC to produce CXCL11, which induces migration of trophoblast cells and T cells, proliferation of ESC, and apoptosis of EEC.