A chemokine, interferon (IFN)-γ-inducible protein 10 kDa, is stimulated by IFN-τ and recruits immune cells in the ovine endometrium
A chemokine, interferon (IFN)-γ-inducible protein 10 kDa, is stimulated by IFN-τ and recruits immune cells in the ovine endometrium
复制标题
DOI：
10.1095/biolreprod.102.008912
复制
发表时间：
2003-04-01
影响因子：
3.6
通讯作者：
Christenson, RK
中科院分区：
文献类型：
--
作者：
Nagaoka, K;Sakai, A;Christenson, RK
免疫细胞在子宫中的适当分布是成功着床和随后胎盘植入的先决条件，但控制这些事件的生化信号尚未得到很好的表征。在本研究中，通过对妊娠第17天和周期第15天的绵羊子宫内膜组织进行的基因消减研究，确定了一种趋化因子干扰素-γ诱导蛋白10 kDa(IP-10)的基因。然后观察干扰素-tau对IP-10表达的影响以及IP-10在免疫细胞募集中的作用。Northern印迹分析显示，在胚胎附着于母体子宫内膜和早期胎盘形成过程中，IP-10mRNA大量表达。IP-10mRNA定位于单核细胞，分布于妊娠子宫上皮下间质，但不定位于周期子宫。IP-10mRNA在单核细胞中的表达，而不是在淋巴细胞、子宫上皮细胞或基质细胞中的表达，支持了这一发现。干扰素-α、干扰素-γ和干扰素-tau均可剂量依赖性地刺激单核细胞表达IP-10mRNA，但干扰素-tau对子宫内膜组织IP-10mRNA的刺激作用最强。在趋化实验中，加入干扰素-tau刺激的子宫内膜培养液可刺激外周血单个核细胞的迁移，这种作用可被抗IP-10抗体中和后显著降低。这些结果表明，胚胎干扰素-tau调控的子宫内膜IP-10调节着妊娠早期子宫中免疫细胞的募集和/或分布。
Proper distribution of immune cells in the uterus is a prerequisite for successful implantation and subsequent placentation, but biochemical signals that govern such events have not been well characterized. In the present study, the cDNA of a chemokine, interferon (IFN)-gamma-inducible protein 10 kDa (IP-10), was identified from a cDNA subtraction study between uterine endometrial tissues from Day 17 pregnant and Day 15 cyclic ewes. The effect of IFN-tau on IP-10 expression and the involvement of IP-10 in the recruitment of immune cells were then investigated. Northern blot analysis revealed that large amounts of IP-10 mRNA were present during conceptus attachment to maternal endometrium and early placentation. IP-10 mRNA was localized to monocytes distributed in the subepithelial stroma of pregnant but not cyclic uteri. This finding was supported by the discovery of IP-10 mRNA expression in monocytes but not in lymphocytes, uterine epithelial cells, or stromal cells. Moreover, the expression of IP-10 mRNA by the monocytes was stimulated by IFN-alpha, IFN-gamma, and IFN-tau in a dose-dependent manner, but the expression of IP-10 mRNA by the endometrial explants was most stimulated by IFN-tau. In a chemotaxis assay, migration of peripheral blood mononuclear cells was stimulated by the addition of IFN-tau stimulated-endometrial culture medium, and the effect was significantly reduced by neutralization with an anti-IP-10 antibody. These results suggest that endometrial IP-10 regulated by conceptus IFN-tau regulates recruitment and/or distribution of immune cells seen in the early pregnant uterus.