HO-1 as modulator of the innate immune response in pregnancy

Am J Reprod Immunol. 2013 Jul;70(1):24-30. doi: 10.1111/aji.12115. Epub 2013 Mar 22.

Abstract

Problem: The immune modulatory effect of heme oxygenase-1 (HO-1) is well documented in studies about sepsis and transplantation. This work evaluates the influence of HO-1 on the innate immune response during pregnancy.

Method of study: Human first-trimester trophoblasts derived from normal pregnancies or spontaneous abortions were analyzed for their basal HO-1, BCL-associated athanogene-1 (Bag-1), and cytokine production before and after LPS treatment. In vivo, pregnant Hmox1+/+ and Hmox1+/- female mice were treated with LPS, and the production of Bag-1 was evaluated.

Results: Human trophoblasts up-regulated the expression of both HO-1 and pro-inflammatory cytokines after LPS treatment, whereas the basal level of HO-1 was higher in normal pregnancies. In vivo, HO-1 deficiency provoked diminished Bag-1 level upon LPS treatment.

Conclusion: HO-1 deficiency causes an inflammatory immune reaction and diminished expression of protective molecules in trophoblasts. Thus, HO-1 emerges as one important modulator of innate immune responses in pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous / immunology*
  • Adult
  • Animals
  • Cells, Cultured
  • Cytokines / immunology
  • DNA-Binding Proteins / immunology*
  • Female
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / immunology*
  • Humans
  • Immunity, Innate
  • Lipopolysaccharides
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Mice
  • Mice, Transgenic
  • Pregnancy / immunology*
  • Transcription Factors / immunology*
  • Trophoblasts / immunology*
  • Young Adult

Substances

  • BCL2-associated athanogene 1 protein
  • Cytokines
  • DNA-Binding Proteins
  • Lipopolysaccharides
  • Membrane Proteins
  • Transcription Factors
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Hmox1 protein, mouse