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Pregnancy |
-Inducible Protein 10 kDa, Is Stimulated by IFN-
and Recruits Immune Cells in the Ovine Endometrium1
a Laboratory of Animal Breeding, Faculty of Agriculture, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan
b National Institute of Animal Health, Tsukuba, Ibaraki 305-0856, Japan
c Reproduction Research Unit, USDA-ARS, U.S. Meat Animal Research Center, Clay Center, Nebraska 68933-0166
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)-
-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-
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-
, IFN-
, and IFN-
in a dose-dependent manner, but the expression of IP-10 mRNA by the endometrial explants was most stimulated by IFN-
. 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-
regulates recruitment and/or distribution of immune cells seen in the early pregnant uterus.
2 Correspondence: Kazuhiko Imakawa, Laboratory of Animal Breeding, Faculty of Agriculture, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. FAX: 81 3 58418180; akaz{at}mail.ecc.u-tokyo.ac.jp
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