Retinoic acid and host-pathogen interactions: Effects on inducible nitric oxide synthase in vivo

Yvan Devaux, Sandrine Grosjean, Carole Seguin, Chantal David, Brigitte Dousset, Faiez Zannad, Claude Meistelman, Nicole De Talancé, Paul Michel Mertes, Dan Ungureanu-Longrois*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

33 Citations (Scopus)


Vitamin A and its metabolite retinoic acid modulate the host response to pathogens through poorly characterized mechanisms. In vitro studies have suggested that retinoic acid decreases inducible NO synthase (NOS2, or iNOS) expression, a component of innate immunity, in several cell types stimulated with lipopolysaccharide (LPS) or cytokines. This study investigated the effect of retinoic acid on LPS-stimulated NOS2 expression in vivo. Wistar-Kyoto rats received all-trans retinoic acid (RA, 10 mg/kg) or vehicle intraperitoneally daily for 5 days followed by LPS (4 mg/kg) or saline intraperitoneally and were killed 6 h later. NOS2 activation was estimated by mRNA (RT-PCR) and protein (Western-blot) expression and plasma nitrate/nitrite accumulation. In sharp contrast to previous in vitro study reports, RA significantly enhanced NOS2 mRNA, protein expression, and plasma nitrate/nitrite concentration in LPS-injected rats but not in saline-injected rats. This was associated with increased expression of interleukin-2, interferon (IFN)-γ and IFN regulatory factor-1 mRNAs in several organs and increased IFN-γ plasma concentration. RA significantly increased mortality in LPS-injected rats. The NOS inhibitor aminoguanidine (50 mg/kg before LPS injection) significantly attenuated the RA-mediated increase in mortality. These results demonstrate for the first time that RA supplementation in vivo enhances activation of the LPS-triggered NOS2 pathway.

Original languageEnglish
Pages (from-to)E1045-E1053
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number5 42-5
Publication statusPublished - 2000
Externally publishedYes


  • Interferon regulatory factor-1
  • Interferon type II
  • Lipopolysaccharide
  • Nitric oxide
  • Retinoids


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