title: Retinoic acid inhibits in vivo interleukin-2 gene expression and T-cell activation in mice.
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.
authors.affiliation: Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Aase
authors.initials: A
authors.lastname: Ertesvag
authors.forename: Liv M I
authors.initials: LM
authors.lastname: Austenaa
authors.forename: Harald
authors.initials: H
authors.lastname: Carlsen
authors.forename: Rune
authors.initials: R
authors.lastname: Blomhoff
authors.forename: Heidi Kiil
authors.initials: HK
authors.lastname: Blomhoff
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014212:Tretinoin / Q000494:pharmacology*; D014802:Vitamin A Deficiency / Q000276:immunology
chemical_list: D001565:Benzoates; D002839:Chromans; D007376:Interleukin-2; D016328:NF-kappa B; D018168:Receptors, Retinoic Acid; C084904:Ro 41-5253; D014212:Tretinoin
references.citation: J Immunol. 1989 Jan 15;142(2):388-93
references.pmid: 2463304
references.citation: J Nutr. 2004 Oct;134(10):2660-6
references.pmid: 15465763
references.citation: J Immunol. 1986 Apr 1;136(7):2348-57
references.pmid: 2419430
references.citation: Curr Opin Immunol. 2002 Jun;14(3):354-9
references.pmid: 11973134
references.citation: Ciba Found Symp. 1985;113:117-31
references.pmid: 3896697
references.citation: Vitam Horm. 2006;74:105-45
references.pmid: 17027513
references.citation: Int Arch Allergy Immunol. 1997 May-Jul;113(1-3):167-9
references.pmid: 9130512
references.citation: Eur J Immunol. 1995 Jun;25(6):1673-9
references.pmid: 7614995
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9358-65
references.pmid: 8790334
references.citation: Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374-8
references.pmid: 2950524
references.citation: J Immunol. 1991 Aug 15;147(4):1247-52
references.pmid: 1907993
references.citation: Crit Care Med. 2002 Jan;30(1 Suppl):S18-26
references.pmid: 11782557
references.citation: Nature. 1995 Sep 28;377(6547):348-51
references.pmid: 7566090
references.citation: J Immunol. 2002 Nov 15;169(10):5555-63
references.pmid: 12421932
references.citation: J Immunol. 1994 Oct 15;153(8):3514-22
references.pmid: 7930573
references.citation: Nature. 1995 Feb 2;373(6513):438-41
references.pmid: 7530335
references.citation: Cytokine. 2004 Nov 7;28(3):109-23
references.pmid: 15473953
references.citation: Science. 1988 Oct 28;242(4878):569-71
references.pmid: 2902689
references.citation: Immunol Today. 1996 Mar;17(3):138-46
references.pmid: 8820272
references.citation: Dev Immunol. 1998;5(4):223-45
references.pmid: 9814581
references.citation: J Immunol. 2006 Sep 1;177(5):2851-61
references.pmid: 16920920
references.citation: J Immunol. 2004 Mar 1;172(5):2731-8
references.pmid: 14978070
references.citation: J Immunol. 2002 May 1;168(9):4495-503
references.pmid: 11970994
references.citation: Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7129-33
references.pmid: 1323127
references.citation: Immunity. 2004 Oct;21(4):527-38
references.pmid: 15485630
references.citation: Annu Rev Nutr. 2001;21:167-92
references.pmid: 11375434
references.citation: J Exp Med. 1992 Jan 1;175(1):111-20
references.pmid: 1730911
references.citation: Int Immunol. 2003 Aug;15(8):1017-25
references.pmid: 12882839
references.citation: Nat Rev Immunol. 2004 Sep;4(9):665-74
references.pmid: 15343366
references.citation: J Immunol. 2002 Feb 1;168(3):1441-6
references.pmid: 11801687
references.citation: J Nutr. 1999 Oct;129(10):1782-90
references.pmid: 10498748
references.citation: Int Immunol. 2004 Mar;16(3):443-53
references.pmid: 14978018
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3810-5
references.pmid: 9520449
references.citation: FASEB J. 2004 Aug;18(11):1255-7
references.pmid: 15180954
references.citation: J Exp Med. 2007 Aug 6;204(8):1765-74
references.pmid: 17620363
references.citation: J Immunol. 1994 Feb 15;152(4):1515-22
references.pmid: 8120366
references.citation: Infect Immun. 1985 May;48(2):581-3
references.pmid: 3886551
references.citation: J Immunol. 1989 Feb 1;142(3):737-43
references.pmid: 2521507
references.citation: Cell Immunol. 1998 Apr 10;185(1):75-81
references.pmid: 9636685
references.citation: Immunology. 1997 Mar;90(3):388-96
references.pmid: 9155646
references.citation: Clin Exp Immunol. 1991 Dec;86(3):537-43
references.pmid: 1721015
references.citation: Immunology. 1993 Dec;80(4):581-6
references.pmid: 8307607
references.citation: J Nutr. 2000 May;130(5):1132-9
references.pmid: 10801909
references.citation: Infect Immun. 1995 Aug;63(8):3062-8
references.pmid: 7622231
references.citation: Proc Nutr Soc. 1999 Aug;58(3):719-27
references.pmid: 10604208