A chemokine, interferon (IFN)-gamma-inducible protein 10 kDa, is stimulated by IFN-tau and recruits immune cells in the ovine endometrium.
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.
Nagaoka
Kentaro
K
Laboratory of Animal Breeding, Faculty of Agriculture, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Sakai
Akiharu
A
Nojima
Hisashi
H
Suda
Yoshihito
Y
Yokomizo
Yuichi
Y
Imakawa
Kazuhiko
K
Sakai
Senkiti
S
Christenson
Ronald K
RK
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003001:Cloning, Molecular; D004717:Endometrium / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D005260:Female; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000235:genetics / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics; D012756:Sheep; D014018:Tissue Distribution
D007370:Interferon Type I; D020382:Interleukin-18; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; C020947:interferon tau; D007371:Interferon-gamma