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