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

Abstract

IFN-γ 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-γ, 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-γ stimulated the protein levels of CXCL11 in a dose-dependent manner in EEC and ESC. CXCL11 secreted from EEC with 100 ng/ml IFN-γ was 220-fold of the control, and 100-fold as compared with that secreted from ESC with the same dose of IFN-γ. CXCR3 was expressed in EEC, ESC, and trophoblast cells. Addition of IFN-γ 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-γ promotes implantation by stimulating EEC to produce CXCL11, which induces migration of trophoblast cells and T cells, proliferation of ESC, and apoptosis of EEC.

Human Chorionic Gonadotropin Attracts Regulatory T Cells into the Fetal-Maternal Interface during Early Human Pregnancy

“…Primary first trimester trophoblast cells were obtained as described elsewhere (42) and further cultured in Medium 199 (Invitrogen) supplemented with 10% FBS (Biochrom) and 50 mg/ml Normocin (Amaxa). Both the choriocarcinoma trophoblast cell line JEG-3 and the skin cell line HaCat were cultured in DMEM normal growth medium (Invitrogen) supplemented with 10% FBS and 100 nM penicillin/streptomycin (Invitrogen).…”

Interleukin-4 Stimulates Proliferation of Endometriotic Stromal Cells

“…21,29 Cultured cells were homogenized in a lysis buffer containing 50 mmol/L Tris/HCl (pH 6.8), 2% sodium dodecyl sulfate, 10% glycerol, 50 mmol/L dithiothreitol, and 0.1% bromophenol blue, and diluted to 1 mg of total protein/ml. Concentrations of total protein in the homogenized cells were measured by a protein assay kit (BioRad Laboratories, Hercules, CA).…”

Deficiency of Immunophilin FKBP52 Promotes Endometriosis

“…Reverse transcription (RT) and quantitative PCR were performed as previously described. 38 The RT reaction was performed using ReverTra Ace-␣ (Toyobo, Osaka, Japan). Quantitative PCR was performed in a LightCycler (Roche Diagnostics GmbH, Mannheim, Germany) using FastStart DNA Master Plus SYBR Green (Roche Diagnostics GmbH).…”