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

• Published in: Biology of reproduction Vol. 68; no. 4; pp. 1413 - 1421
• Main Authors: Nagaoka, K, Sakai, A, Nojima, H, Suda, Y, Yokomizo, Y, Imakawa, K, Sakai, S, Christenson, R.K
• Format: Journal Article
• Language: English
• Published: United States 01.04.2003
• Subjects: Amino Acid Sequence - genetics; amino acid sequences; Animals; Cell Movement - drug effects; chemokine receptor 3; chemotaxis; Cloning, Molecular; complementary DNA; conceptus; cytokines; embryo implantation; endometrium; Endometrium - cytology; Endometrium - drug effects; Endometrium - immunology; estrous cycle; ewes; Female; gene expression regulation; immune cell recruitment; immunity; In Vitro Techniques; Interferon Type I - genetics; Interferon Type I - pharmacology; Interferon-gamma - genetics; Interferon-gamma - pharmacology; interferons; Interleukin-18 - genetics; Interleukin-18 - metabolism; Interleukin-18 - pharmacology; Interleukin-18 - physiology; messenger RNA; Molecular Sequence Data; monocytes; Monocytes - physiology; mononuclear cell migration; nucleotide sequences; Pregnancy; Pregnancy Proteins - genetics; Pregnancy Proteins - pharmacology; receptors; Receptors, Chemokine - genetics; Receptors, CXCR3; RNA, Messenger - metabolism; Sheep; temporal variation; Tissue Distribution
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1043/0006-3363(2003)068(1413:ACIIIP)2.0.CO;2

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)-γ-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-taú 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-α, IFN-γ, 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- 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.