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

Hum Reprod. 2007 Oct;22(10):2733-42. doi: 10.1093/humrep/dem208. Epub 2007 Aug 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Butadienes / pharmacology
  • Chemokine CCL2 / biosynthesis*
  • Chorionic Gonadotropin / pharmacology
  • Decidua / cytology
  • Decidua / metabolism*
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Female
  • Fulvestrant
  • Gene Expression Regulation, Developmental
  • Humans
  • Nitriles / pharmacology
  • Pregnancy
  • Pregnancy Trimester, First
  • Progesterone / pharmacology
  • Receptors, CCR2 / biosynthesis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / metabolism*
  • Up-Regulation

Substances

  • Butadienes
  • CCL2 protein, human
  • CCR2 protein, human
  • Chemokine CCL2
  • Chorionic Gonadotropin
  • Nitriles
  • Receptors, CCR2
  • U 0126
  • Fulvestrant
  • Progesterone
  • Estradiol
  • Extracellular Signal-Regulated MAP Kinases