Inhibition of eIF5A results in aberrant uterine natural killer cell function and embryo loss in mice

Am J Reprod Immunol. 2014 Mar;71(3):229-40. doi: 10.1111/aji.12194. Epub 2014 Jan 2.

Abstract

Problem: The role of eukaryotic initiation factor 5A (eIF5A) in feto-maternal immunotolerance is poorly understood.

Methods of study: The effects of N1-guanyl-1,7-diaminoheptane (GC7), an inhibitor of eIF5A, on the proportion and function of natural killer (NK) cell subsets were investigated using flow cytometry, immunofluorescence, CCK8 assay, TUNEL assay, DNA fragmentation analysis, mitochondrial membrane potential assay, and Western blotting.

Results: Inhibition of eIF5A by GC7 increased embryo loss and reduced the percentage of NK cells in the uterus and spleen. GC7 treatment caused inhibition of NK cell proliferation in a time- and dose-dependent manner. GC7 also induced apoptosis of NK cells. GC7 treatment increased the protein levels of FasL, bax, p53, and cleaved caspase-3. Moreover, GC7 caused loss of mitochondrial membrane potential in NK cells.

Conclusion: Inhibition of eIF5A results in aberrant NK cell function and increased embryo loss.

Keywords: Abortion; GC7; apoptosis; eIF5A; natural killer cell.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Embryo Loss / immunology*
  • Eukaryotic Translation Initiation Factor 5A
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives*
  • Guanine / pharmacology
  • Immune Tolerance
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Peptide Initiation Factors / antagonists & inhibitors
  • Peptide Initiation Factors / genetics
  • Peptide Initiation Factors / metabolism*
  • Pregnancy
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Spleen / drug effects
  • Spleen / immunology
  • Uterus / drug effects
  • Uterus / immunology*

Substances

  • Apoptosis Regulatory Proteins
  • N(1)-guanyl-1,7-diaminoheptane
  • Peptide Initiation Factors
  • RNA-Binding Proteins
  • Guanine