A chemokine, interferon (IFN)-gamma-inducible protein 10 kDa, is stimulated by IFN-tau and recruits immune cells in the ovine endometrium.

A chemokine, interferon (IFN)-gamma-inducible protein 10 kDa, is stimulated by IFN-tau and recruits immune cells in the ovine endometrium.
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DOI:
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发表时间:
2003
影响因子:
3.6
通讯作者:
K. Nagaoka;A. Sakai;H. Nojima;Y. Suda;Y. Yokomizo;K. Imakawa;S. Sakai;R. Christenson
K. Nagaoka;A. Sakai;H. Nojima;Y. Suda;Y. Yokomizo;K. Imakawa;S. Sakai;R. Christenson
中科院分区:
生物学2区
文献类型:
--
作者:
K. Nagaoka;A. Sakai;H. Nojima;Y. Suda;Y. Yokomizo;K. Imakawa;S. Sakai;R. Christenson

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免疫细胞在子宫中的适当分布是成功着床和随后胎盘形成的先决条件,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,一种趋化因子,干扰素(IFN)-γ-诱导蛋白10 kDa(IP-10)的cDNA,确定了从子宫内膜组织从第17天怀孕和第15天周期母羊之间的cDNA消减研究。然后研究IFN-tau对IP-10表达的影响和IP-10参与免疫细胞募集的情况。北方印迹分析显示,IP-10 mRNA在妊娠期子宫内膜附着和胎盘形成早期大量表达。IP-10 mRNA定位于单核细胞分布在上皮下基质的怀孕,但不是周期子宫。这一发现得到了单核细胞中IP-10 mRNA表达而淋巴细胞、子宫上皮细胞或基质细胞中不表达的发现的支持。此外,单核细胞的IP-10 mRNA的表达以剂量依赖性方式被IFN-α、IFN-γ和IFN-τ刺激,但子宫内膜外植体的IP-10 mRNA的表达最受IFN-τ刺激。在趋化性测定中,通过加入IFN-τ刺激的子宫内膜培养基刺激外周血单核细胞的迁移,并且通过用抗IP-10抗体中和显著降低该作用。这些结果表明,由孕体IFN-tau调节的子宫内膜IP-10调节在早期妊娠子宫中观察到的免疫细胞的募集和/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.