Differentiation-induced post-transcriptional control of B7-H1 in human trophoblast cells

Placenta. 2009 Jan;30(1):48-55. doi: 10.1016/j.placenta.2008.10.001. Epub 2008 Nov 17.


Trophoblast expression of immunomodulatory proteins in the human placenta is among the mechanisms that are critical for ensuring lymphocyte tolerance to the semi-allogeneic fetus. High levels of B7-H1 on trophoblast cells together with the known role of this protein in establishment of peripheral tolerance suggest that B7-H1 mediates immunological protection of the placenta during gestation. In this study, we investigated the molecular mechanisms of regulation of B7-H1 in trophoblast cells by epidermal growth factor (EGF), a key regulator of trophoblast cell differentiation. EGF increased B7-H1 protein levels within 24 h and mRNA levels within 4h of the initiation of treatment; by 24 h B7-H1 mRNA levels were similar between control and EGF-treated cells. Analysis of two different potential promoter regions revealed strong promoter activity in response to IFN-gamma. In contrast, no promoter activity could be induced by EGF, suggesting that this cytokine regulates B7-H1 expression post-transcriptionally in trophoblast cells. EGF-induced B7-H1 protein expression was completely blocked in the presence of inhibitors of the PI3Kinase/Akt/mTOR pathway, a pathway known to regulate gene expression at the translational level. Finally, analysis of monosomal and polysomal mRNA fractions of untreated and EGF-treated term trophoblast cells revealed that EGF induces a shift towards the translatable fractions and away from the untranslated fractions. These results highlight a novel mechanism for regulation of B7 family proteins in the placenta.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • B7-H1 Antigen
  • Cell Differentiation / physiology*
  • Cell Fusion
  • Cell Separation
  • Cells, Cultured
  • Chorionic Villi
  • Enzyme Inhibitors / pharmacology
  • Epidermal Growth Factor / pharmacology
  • Female
  • Gene Expression
  • Humans
  • Interferon-gamma / pharmacology
  • Pregnancy
  • Protein Processing, Post-Translational / drug effects
  • Protein Processing, Post-Translational / physiology*
  • RNA, Messenger / metabolism
  • Trophoblasts / cytology*
  • Trophoblasts / metabolism
  • Young Adult


  • Antigens, CD
  • B7-H1 Antigen
  • CD274 protein, human
  • Enzyme Inhibitors
  • RNA, Messenger
  • Epidermal Growth Factor
  • Interferon-gamma