The Expression and Possible Roles of Chemokine CXCL11 and Its Receptor CXCR3 in the Human Endometrium

• Published in: Journal of Immunology 2006-12, Vol.177 (12), p.8813-8821
• Main Authors: Hirota, Yasushi, Osuga, Yutaka, Koga, Kaori, Yoshino, Osamu, Hirata, Tetsuya, Morimoto, Chieko, Harada, Miyuki, Takemura, Yuri, Nose, Emi, Yano, Tetsu, Tsutsumi, Osamu, Taketani, Yuji
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Chemokine CXCL11; Chemokines, CXC - genetics; Chemokines, CXC - physiology; Chemotaxis - drug effects; Endometrium - chemistry; Endometrium - cytology; Endometrium - metabolism; Epithelial Cells - metabolism; Female; Gene Expression Regulation - drug effects; Humans; Interferon-gamma - pharmacology; Receptors, Chemokine - genetics; Receptors, Chemokine - physiology; Receptors, CXCR3; Stromal Cells - cytology; Stromal Cells - metabolism; T-Lymphocytes - cytology; Trophoblasts - cytology; Trophoblasts - metabolism
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.177.12.8813

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.