Innate immunity in the vagina (part I): estradiol inhibits HBD2 and elafin secretion by human vaginal epithelial cells

Am J Reprod Immunol. 2013 May;69(5):463-74. doi: 10.1111/aji.12078. Epub 2013 Feb 8.

Abstract

Problem: Vaginal epithelial cells (VEC) are the first line of defense against incoming pathogens in the female reproductive tract. Their ability to produce the anti-HIV molecules elafin and HBD2 under hormonal stimulation is unknown.

Method of study: Vaginal epithelial cells were recovered using a menstrual cup and cultured overnight prior to treatment with estradiol (E₂), progesterone (P₄) or a panel of selective estrogen response modulators (SERMs). Conditioned media were recovered and analyzed for protein concentration and anti-HIV activity.

Results: E₂ significantly decreased the secretion of HBD2 and elafin by VEC over 48 hrs, while P4 and the SERMs (tamoxifen, PHTTP, ICI or Y134) had no effect. VEC conditioned media from E₂ -treated cells had no anti-HIV activity, while that from E₂ /P₄ -treated cells significantly inhibited HIV-BaL infection.

Conclusion: The menstrual cup allows for effective recovery of primary VEC. Their production of HBD2 and elafin is sensitive to E₂, suggesting that innate immune protection varies in the vagina across the menstrual cycle.

Publication types

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

MeSH terms

  • Adult
  • Anti-HIV Agents / analysis
  • Cells, Cultured
  • Culture Media, Conditioned / chemistry
  • Elafin / analysis
  • Elafin / metabolism*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / immunology
  • Estradiol / pharmacology*
  • Female
  • Humans
  • Immunity, Innate
  • Middle Aged
  • Progesterone / pharmacology
  • Selective Estrogen Receptor Modulators / pharmacology
  • Vagina / cytology
  • Vagina / immunology*
  • beta-Defensins / analysis
  • beta-Defensins / metabolism*

Substances

  • Anti-HIV Agents
  • Culture Media, Conditioned
  • DEFB4A protein, human
  • Elafin
  • Selective Estrogen Receptor Modulators
  • beta-Defensins
  • Progesterone
  • Estradiol