Retinoic Acid Inhibits in Vivo interleukin-2 Gene Expression and T-cell Activation in Mice

Immunology. 2009 Apr;126(4):514-22. doi: 10.1111/j.1365-2567.2008.02913.x. Epub 2008 Sep 4.

Abstract

Interleukin-2 (IL-2) is an essential cytokine for T-lymphocyte homeostasis. We have previously reported that all-trans retinoic acid (atRA) enhances the secretion of IL-2 from human peripheral blood T cells in vitro, followed by increased proliferation and inhibition of spontaneous cell death. In this study we used a transgenic IL-2 gene luciferase reporter model to examine the effects of atRA in vivo. In contrast to the observations in human T cells, we found an overall reduction in luciferase-reported IL-2 gene expression in mice treated with atRA. Whole-body luminescence of anti-CD3-treated and non-treated mice was reduced in mice receiving atRA. Accordingly, after 7 hr, IL-2 gene expression was on average 55% lower in the atRA-treated mice compared with the control mice. Furthermore, mice fed a vitamin A-deficient diet had a significantly higher basal level of luciferase activity compared with control mice, demonstrating that vitamin A modulates IL-2 gene expression in vivo. Importantly, the atRA-mediated inhibition of IL-2 gene expression was accompanied by decreased DNA synthesis in murine T cells, suggesting a physiological relevance of the reduced IL-2 gene expression observed in transgenic reporter mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoates / pharmacology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chromans / pharmacology
  • Female
  • Gene Expression Regulation / drug effects
  • Interleukin-2 / biosynthesis*
  • Interleukin-2 / genetics
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Transgenic
  • NF-kappa B / metabolism
  • Receptors, Retinoic Acid / antagonists & inhibitors
  • Receptors, Retinoic Acid / immunology
  • Spleen / immunology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Tretinoin / pharmacology*
  • Vitamin A Deficiency / immunology

Substances

  • Benzoates
  • Chromans
  • Interleukin-2
  • NF-kappa B
  • Receptors, Retinoic Acid
  • Ro 41-5253
  • Tretinoin