Docosahexaenoic acid, a constituent of fetal and neonatal serum, inhibits nitric oxide production by murine macrophages stimulated by IFNγ plus LPS, or by IFNγ plus Listeria monocytogenes

C. Y. Lu, J. G. Penfield, T. A. Khair-El-Din, S. C. Sicher, M. L. Kielar, M. A. Vazquez, L. Che

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Murine macrophage activation is deficient in the fetus and the neonate, and in areas of the placenta perfused by the fetal circulation. Fetal and neonatal serum concentrations of docosahexaenoic acid (DHA) are 150 μM, or ≃ 50-fold higher than in the adult. We previously showed that DHA inhibits activation of the gene for inducible nitric oxide synthase (iNOS) in murine macrophages stimulated in vitro with interferon γ (IFNγ) plus lipopolysaccharide (LPS). We have now pursued these observations in greater depth. An assay system was developed which separated the stimulation of macrophages by IFNγ plus LPS, and the actual production of nitric oxide (NO). It was found that macrophages do not produce NO until they have been stimulated by IFNγ plus LPS for a period of 10 h. NO is produced during the subsequent 10 h, even though IFNγ, plus LPS are not longer present. DHA, if present, inhibited only during the initial 10 h stimulation; DHA did not inhibit the production of NO by macrophages which had previously been stimulated by IFNγ plus LPS, and were already producing NO. It was also found that DHA was less inhibitory if given prior to the IFNγ plus LPS stimulation. In a dose-responsive manner, DHA inhibited the increased abundance of iNOS mRNA by macrophages stimulated by IFNγ plus LPS. NO contributes to the host defense against Listeria monocytogenes and other intracellular pathogens. We therefore investigated the ability of DHA to inhibit NO production by macrophages stimulated by IFNγ, plus Listeria monocytogenes in vitro; DHA inhibited transcription of the iNOS gene and also the listeriocidal activity of activated macrophages. Inhibition of NO production by DHA may contribute to the increased susceptibility of the fetoplacental unit and neonate to intracellular infections.

Original languageEnglish (US)
Pages (from-to)31-53
Number of pages23
JournalJournal of Reproductive Immunology
Volume38
Issue number1
DOIs
StatePublished - Apr 1 1998

Keywords

  • Interferon γ
  • Lipopolysaccharide
  • Listeria monocytogenes
  • Monocytes/macrophages
  • Nitric oxide
  • Pregnancy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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