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Title 

Regulation of blastocyst migration, apposition, and initial adhesion by a chemokine, interferon γ-inducible protein 10 kDa (IP-10), during early gestation

Authors 

K NagaokaH NojimaF WatanabeKyu Tae ChangR K ChristensonS SakaiK Imakawa

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

2003

Citation 

Journal of Biological Chemistry, vol. 278, no. 31, pp. 29048-29056

Keywords 

adhesionchemical bondstrophoblast cellsproteinsalpha5 integrinamino acidantibodyarginineaspartic acidbeta1 integrin

Abstract 

For a pregnancy to be established, initial apposition and adhesion of the blastocyst to maternal endometrium must occur in a coordinated manner; however, a key factor(s) that mediates the trophoblast cell migration and attachment to the apical surface of the endometrium has not been identified. In this study, we examined the effect of an endometrial chemokine, interferonγ-inducible protein 10 kDa (IP-10), on conceptus migration to the endometrial epithelium. We first studied endometrial IP-10 mRNA expression, which was localized in the subepithelial stromal region, and detected the protein in the uterine flushing media during early pregnancy. Expression of IP-10 mRNA by the endometrium of cyclic animals was stimulated by the addition of a conceptus factor interferon-tau (IFN-τ). Immunofluorescent analysis revealed that IP-10 receptor, CXCR3, was localized in the trophoblast cells, to which biotinylated-recombinant caprine IP-10 (rcIP-10) bound. Chemotaxis assay indicated that rcIP-10 stimulated the migration of trophoblast cells, and the effects of rcIP-10 were neutralized by the pretreatment with an anti-IP-10 antibody. Adhesive activity of trophoblast cells to fibronectin was promoted by rcIP-10, and the effect was inhibited by the use of anti-IP-10 antibody. Further adhesion experiments demonstrated that binding of trophoblast cells to fibronectin was completely inhibited by a peptide of the Arg-Gly-Asp (RGD) sequence, which binds to integrins α5β1, αvβ1, αvβ3, and αvβ5, whereas non-binding peptide containing Arg-Gly-Glu (RGE) had minimal effects. More importantly, rcIP-10 promoted the adhesion of trophoblast cells to primary cells isolated from endometrial epithelium. Furthermore, rcIP-10 stimulated the expression of integrin α5, αv, and β3 subunit mRNA in trophoblast cells. These findings suggest that endometrial IP-10 regulates the establishment of apical interactions between trophoblast and epithelial cells during early gestation.

ISSN 

0021-9258

Link 

http://dx.doi.org/10.1074/jbc.M300470200

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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