Retinoid X receptor agonists increase Bcl2a1 expression and decrease apoptosis of naive T lymphocytes

Reuven Rasooly, Gertrud U. Schuster, Jeffrey Gregg, Jia Hao Xiao, Roshantha A S Chandraratna, Charles B. Stephensen

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Vitamin A affects many aspects of T lymphocyte development and function. The vitamin A metabolites all-trans- and 9-cis-retinoic acid regulate gene expression by binding to the retinoic acid receptor (RAR), while 9-cis-retinoic acid also binds to the retinoid X receptor (RXR). Naive DO11.10 T lymphocytes expressed mRNA and protein for RAR-α, RXR-α, and RXR-β. DNA microarray analysis was used to identify RXR-responsive genes in naive DO11.10 T lymphocytes treated with the RXR agonist AGN194204. A total of 128 genes was differentially expressed, including 16 (15%) involved in cell growth or apoptosis. Among these was Bcl2a1, an antiapoptotic Bcl2 family member. Quantitative real-time PCR analysis confirmed this finding and demonstrated that Bcl2a1 mRNA expression was significantly greater in nonapoptotic than in apoptotic T lymphocytes. The RXR agonist 9-cis-retinoic acid also increased Bcl2a1 expression, although all-trans-retinoic acid and ligands for other RXR partner receptors did not. Treatment with AGN194204 and 9-cis-retinoic acid significantly decreased apoptosis measured by annexin V staining but did not affect expression of Bcl2 and Bcl-xL. Bcl2a1 promoter activity was examined using a luciferase promoter construct. Both AGN194204 and 9-cis-retinoic acid significantly increased luciferase activity. In summary, these data demonstrate that RXR agonists increase Bcl2a1 promoter activity and increase expression of Bcl2a1 in naive T lymphocytes but do not affect Bcl2 and Bcl-xL expression in naive T lymphocytes. Thus, this effect on Bcl2a1 expression may account for the decreased apoptosis seen in naive T lymphocytes treated with RXR agonists.

Original languageEnglish (US)
Pages (from-to)7916-7929
Number of pages14
JournalJournal of Immunology
Volume175
Issue number12
StatePublished - Dec 15 2005

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Retinoid X Receptors
Apoptosis
T-Lymphocytes
Retinoic Acid Receptors
Luciferases
Vitamin A
Messenger RNA
Annexin A5
Microarray Analysis
Tretinoin
Oligonucleotide Array Sequence Analysis
Genes
Real-Time Polymerase Chain Reaction
Staining and Labeling
Ligands

ASJC Scopus subject areas

  • Immunology

Cite this

Rasooly, R., Schuster, G. U., Gregg, J., Xiao, J. H., Chandraratna, R. A. S., & Stephensen, C. B. (2005). Retinoid X receptor agonists increase Bcl2a1 expression and decrease apoptosis of naive T lymphocytes. Journal of Immunology, 175(12), 7916-7929.

Retinoid X receptor agonists increase Bcl2a1 expression and decrease apoptosis of naive T lymphocytes. / Rasooly, Reuven; Schuster, Gertrud U.; Gregg, Jeffrey; Xiao, Jia Hao; Chandraratna, Roshantha A S; Stephensen, Charles B.

In: Journal of Immunology, Vol. 175, No. 12, 15.12.2005, p. 7916-7929.

Research output: Contribution to journalArticle

Rasooly, R, Schuster, GU, Gregg, J, Xiao, JH, Chandraratna, RAS & Stephensen, CB 2005, 'Retinoid X receptor agonists increase Bcl2a1 expression and decrease apoptosis of naive T lymphocytes', Journal of Immunology, vol. 175, no. 12, pp. 7916-7929.
Rasooly R, Schuster GU, Gregg J, Xiao JH, Chandraratna RAS, Stephensen CB. Retinoid X receptor agonists increase Bcl2a1 expression and decrease apoptosis of naive T lymphocytes. Journal of Immunology. 2005 Dec 15;175(12):7916-7929.
Rasooly, Reuven ; Schuster, Gertrud U. ; Gregg, Jeffrey ; Xiao, Jia Hao ; Chandraratna, Roshantha A S ; Stephensen, Charles B. / Retinoid X receptor agonists increase Bcl2a1 expression and decrease apoptosis of naive T lymphocytes. In: Journal of Immunology. 2005 ; Vol. 175, No. 12. pp. 7916-7929.
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abstract = "Vitamin A affects many aspects of T lymphocyte development and function. The vitamin A metabolites all-trans- and 9-cis-retinoic acid regulate gene expression by binding to the retinoic acid receptor (RAR), while 9-cis-retinoic acid also binds to the retinoid X receptor (RXR). Naive DO11.10 T lymphocytes expressed mRNA and protein for RAR-α, RXR-α, and RXR-β. DNA microarray analysis was used to identify RXR-responsive genes in naive DO11.10 T lymphocytes treated with the RXR agonist AGN194204. A total of 128 genes was differentially expressed, including 16 (15{\%}) involved in cell growth or apoptosis. Among these was Bcl2a1, an antiapoptotic Bcl2 family member. Quantitative real-time PCR analysis confirmed this finding and demonstrated that Bcl2a1 mRNA expression was significantly greater in nonapoptotic than in apoptotic T lymphocytes. The RXR agonist 9-cis-retinoic acid also increased Bcl2a1 expression, although all-trans-retinoic acid and ligands for other RXR partner receptors did not. Treatment with AGN194204 and 9-cis-retinoic acid significantly decreased apoptosis measured by annexin V staining but did not affect expression of Bcl2 and Bcl-xL. Bcl2a1 promoter activity was examined using a luciferase promoter construct. Both AGN194204 and 9-cis-retinoic acid significantly increased luciferase activity. In summary, these data demonstrate that RXR agonists increase Bcl2a1 promoter activity and increase expression of Bcl2a1 in naive T lymphocytes but do not affect Bcl2 and Bcl-xL expression in naive T lymphocytes. Thus, this effect on Bcl2a1 expression may account for the decreased apoptosis seen in naive T lymphocytes treated with RXR agonists.",
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AU - Chandraratna, Roshantha A S

AU - Stephensen, Charles B.

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