Regulation of C-C motif chemokine ligand 2 and its receptor in human decidual stromal cells by pregnancy-associated hormones in early gestation.

BACKGROUND Decidua is in close contact with the fetal trophoblasts, and involved in immune relationship of mother to fetus. However, the roles of decidua and decidual stromal cells (DSC) in materno-fetal immune regulation remain to be elucidated. In the present study, the expression and regulation of chemokines and their receptors in decidua and DSCs were investigated. METHODS AND RESULTS The transcription of 18 chemokine receptors in human first-trimester decidual tissue and DSC were first analysed by RT-PCR. Among these receptors, C-C motif chemokine receptor-2 (CCR2) was highly transcribed. It was demonstrated by RT-PCR and immunostaining that both CCR2 and its major ligand, C-C motif chemokine ligand 2 (CCL2, monocyte chemoattractant protein-1), were expressed in decidua and DSC. We then detected CCL2 in the supernatant of primary cultures of DSC by enzyme-linked immunosorbent assay. It was shown that DSC secreted CCL2 spontaneously and continuously over 72 h (21.72 +/- 2.34 ng/ml), and the CCR2 antagonist RS102895 and an inhibitor of the map kinase kinase/mitogen-activated protein kinase (ERK/MAPK) signal pathway decreased significantly the CCL2 secretion of DSC (both P < 0.05). We further studied effects of the pregnancy-associated hormones, estrogen, progesterone or HCG on CCL2 secretion by DSC. CCL2 secretion by DSC was up-regulated by estrogen, progesterone or HCG. CONCLUSIONS CCR2 and CCL2 are co-expressed by human first-trimester DSC and decidual tissue. CCL2 is secreted in an autocrine manner through the ERK/MAPK pathway, and is up-regulated by the pregnancy-associated hormones, estrogen, progesterone and HCG, which suggests that CCL2 may play an important role at materno-fetal interface.