Modulation of the expression of the transcription factors T-bet and GATA-3 in immortalized human endometrial stromal cells (HESCs) by sex steroid hormones and cAMP

Reprod Sci. 2013 Jun;20(6):699-709. doi: 10.1177/1933719112466297. Epub 2013 Jan 10.


T-bet and GATA-3 are known to regulate cytokine expression in T lymphocytes, and cytokines have been implicated in endometrial regulation and implantation. Previous work showed that female steroid hormones modulate the expression of T-bet in endometrial epithelial cells, suggesting a mechanism for local immune regulation in the human endometrium. We hypothesized that stromal cells are involved in immune regulation, as they have been shown to exert paracrine effects on other endometrial cells and compartments and also secrete cytokines. The objective of this study was to examine the modulation of the gene expression of T-bet and GATA-3, and of the cytokines interferon γ (IFN-γ) and interleukin 4 (IL-4), by female steroid hormones, in human endometrial stromal cells (HESC) in long-term cultures (30 days) mimicking the normal menstrual cycle. T-bet and GATA-3 messenger RNA (mRNA) expression was detected by real-time polymerase chain reaction, and intracellular protein production was demonstrated by immunoblotting. In addition, secretion of IL-4 and IL-15 was measured by enzyme-linked immunosorbent assay. T-bet and IL-4 mRNA expression increased and GATA-3 decreased under decidualization conditions; IFN-γ was not detected. Secretion of IL-15 increased during decidualization, and IL-15 upregulated T-bet gene expression. In conclusion, gene expression of T-bet and GATA-3 by endometrial stromal cells is under hormonal conditions mimicking decidualization, and the results are consistent with an autocrine regulatory mechanism of IL-15 secretion and T-bet expression.

Keywords: GATA-3; T-bet; gene expression; human; stromal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Transformed
  • Cyclic AMP / pharmacology*
  • Decidua / drug effects
  • Decidua / metabolism
  • Endometrium / drug effects*
  • Endometrium / immunology
  • Endometrium / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Estradiol / pharmacology*
  • Female
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism*
  • Gene Expression Regulation
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-15 / metabolism
  • Interleukin-4 / metabolism
  • Phenotype
  • Progesterone / pharmacology*
  • Prolactin / metabolism
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / drug effects*
  • Stromal Cells / immunology
  • Stromal Cells / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*
  • Time Factors


  • GATA3 Transcription Factor
  • GATA3 protein, human
  • IFNG protein, human
  • IL15 protein, human
  • IL4 protein, human
  • Interleukin-15
  • RNA, Messenger
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interleukin-4
  • Progesterone
  • Estradiol
  • Interferon-gamma
  • Prolactin
  • Cyclic AMP