Potential role of heat-shock protein 70 and interleukin-15 in the pathogenesis of threatened spontaneous abortions

Am J Reprod Immunol. 2016 Aug;76(2):126-36. doi: 10.1111/aji.12525. Epub 2016 May 26.

Abstract

Problem: The role of HSP70 and both its constitutive (Hsc) and inducible (Hsp) forms in the pathogenesis of threatened spontaneous abortions was investigated.

Method of study: Immunohistology and/or immunofluorescence was used to analyze paraffin-embedded tissue sections, and reverse transcriptase-quantitative polymerase chain reaction and flow cytometry were used for analyses of decidual mononuclear cells (DMCs) and confocal microscopy for the detection of perforin, granulysin, and lysosome-associated membrane protein-1 (LAMP-1) in decidual lymphocytes (DLs).

Results: The percentage of single Hsp70(+) , Hsc70(+) , and IL-15(+) cells and mRNA levels of HSP70, CD91, and TLR4 were lower in the decidua basalis in cases of threatened miscarriages compared to that in cases of normal pregnancy. In a suspension of normal DMCs, IL-15 significantly decreased the HSP70 members and TLR4 in dendritic cells, T cells, and NK cells while increasing CD91 in NK cells alone.

Conclusion: Downregulation of Hsc70, Hsp70, and IL-15 expression at gene and/or protein levels might support the retention of fertilization products in cases of missed abortion and blighted ovum.

Keywords: granulysin; heat-shock protein 70; interleukin-15; pathological pregnancy; perforin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous / immunology*
  • Abortion, Spontaneous / pathology
  • Adult
  • Decidua / immunology*
  • Decidua / pathology
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Down-Regulation / immunology
  • Female
  • HSC70 Heat-Shock Proteins / immunology*
  • Humans
  • Interleukin-15 / immunology*
  • Killer Cells, Natural / pathology
  • Low Density Lipoprotein Receptor-Related Protein-1 / immunology
  • Pregnancy
  • Toll-Like Receptor 4 / immunology

Substances

  • HSC70 Heat-Shock Proteins
  • HSPA8 protein, human
  • IL15 protein, human
  • Interleukin-15
  • LRP1 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-1
  • TLR4 protein, human
  • Toll-Like Receptor 4