Chemokine CCL24 promotes the growth and invasiveness of trophoblasts through ERK1/2 and PI3K signaling pathways in human early pregnancy

Abstract

Chemokine CCL24, acting through receptor CCR3, is a potent chemoattractant for eosinophil in allergic diseases and parasitic infections. We recently reported that CCL24 and CCR3 are co-expressed by trophoblasts in human early pregnant uterus. Here we prove with evidence that steroid hormones estradiol (E), progesterone (P), and human chorionic gonadotropin(hCG), aswell as decidual stromal cells (DSCs) could regulate the expression of CCL24 and CCR3 of trophoblasts.We further investigate how trophoblast-derived CCL24mediates the function of trophoblasts in vitro, and conclude that CCL24/CCR3 promotes the proliferation, viability and invasiveness of trophoblasts. In addition, analysis of the downstream signaling pathways of CCL24/CCR3 show that extracellular signal-regulated kinases (ERK1/2) and phosphoinositide 3-kinase (PI3K) pathways may contribute to the proliferation, viability and invasiveness of trophoblasts by activating intracellularmolecules Ki67 andmatrixmetallopeptidase 9 (MMP9).However,we did not observe any inhibitory effect on trophoblastswhen blockingc-JunN-terminal kinase (JNK) orp38pathways. In conclusion,ourdata suggests that trophoblast-derivedCCL24 at thematernal-fetal interface promotes trophoblasts cell growth and invasiveness by ERK1/2 and PI3K pathways.Meanwhile, pregnancy-related hormones (Pand hCG), aswell asDSCs could up-regulate CCL24/CCR3 expression in trophoblasts, which may indirectly influence the biological functions of trophoblasts. Thus, our results provide a possible explanation for the growth and invasion of trophoblasts in human embryo implantation.