The expression and possible roles of chemokine CXCL11 and its receptor CXCR3 in the human endometrium.
IFN-gamma secreted by a human embryo and trophoblast cells during implantation is suggested to play an important role in implantation and pregnancy. In the present study, we explored expression and possible functions of CXCL11, a CXC chemokine strongly induced by IFN-gamma, and its receptor CXCR3 in the human endometrium. Secreted CXCL11 protein was not detected in cultured endometrial stromal cells (ESC) but was detected in cultured endometrial epithelial cells (EEC). IFN-gamma stimulated the protein levels of CXCL11 in a dose-dependent manner in EEC and ESC. CXCL11 secreted from EEC with 100 ng/ml IFN-gamma was 220-fold of the control, and 100-fold as compared with that secreted from ESC with the same dose of IFN-gamma. CXCR3 was expressed in EEC, ESC, and trophoblast cells. Addition of IFN-gamma to EEC increased the chemotactic activity of its culture medium to trophoblast cells and T cells, and the effect was suppressed by immunoneutralization with Abs of three CXCR3 ligands, including anti-CXCL11 Ab. CXCL11 significantly increased BrdU incorporation of ESC, which was inhibited by a p42/44 MAPK pathway inhibitor PD98059. In contrast, CXCL11 significantly decreased BrdU incorporation and increased the release of lactate dehydrogenase and the positive staining of annexin V in EEC. These findings suggest that IFN-gamma promotes implantation by stimulating EEC to produce CXCL11, which induces migration of trophoblast cells and T cells, proliferation of ESC, and apoptosis of EEC.
Hirota
Yasushi
Y
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Osuga
Yutaka
Y
Koga
Kaori
K
Yoshino
Osamu
O
Hirata
Tetsuya
T
Morimoto
Chieko
C
Harada
Miyuki
M
Takemura
Yuri
Y
Nose
Emi
E
Yano
Tetsu
T
Tsutsumi
Osamu
O
Taketani
Yuji
Y
D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054371:Chemokine CXCL11; D019743:Chemokines, CXC / Q000235:genetics / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects; D004717:Endometrium / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
C515202:CXCL11 protein, human; C515187:CXCR3 protein, human; D054371:Chemokine CXCL11; D019743:Chemokines, CXC; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma