Soluble Human Leukocyte Antigen-G5 Activates Extracellular Signal-Regulated Protein Kinase Signaling and Stimulates Trophoblast Invasion

摘要: Soluble human leukocyte antigen-G (HLA-G) is a non-classical class Ib HLA molecule that secreted from blastocysts. HLA-G modulates the immune tolerance of mother and can be used as prognostic factor for clinical pregnancy rate. However, underlying mechanism how soluble HLA-G5 affects remains largely unknown. We hypothesized promotes successful implantation by modulating trophoblast invasion through receptor binding activation extracellular signal-regulated protein kinase (ERK) signaling pathway. Recombinant over-expressed in E. coli BL21 was purified to near homogeneity. studied expression its receptors, immunoglobulin-like subfamily B1 (LILRB1) killer cell 2DL4 (KIR2DL4), primary trophoblasts trophoblastic (JAr JEG-3) lines florescence-labeled HLA-G5. detected JEG-3 cells. The LILRB1 KIR2DL4 receptors were expressed both lines. stimulated (p<0.05) increased urokinase (uPA) matrix metalloproteinases (MMPs) transcripts their activity activated ERK pathway induced ERK1/2 phosphorylation Addition inhibitors (U0126 PD98059) nullified stimulatory effect on invasion. Taken together, LILRB1, increasing uPA MMPs expressions activating