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PMID: 18416830 Published · epublish English Comparative Study Journal Article Research Support, N.I.H., Intramural

The Retinoic Acid Receptor-alpha mediates human T-cell activation and Th2 cytokine and chemokine production.

BMC immunology ·Vol. 9 ·2008-04-16 ·Pages 16

Dawson HD, Collins G, Pyle R, Key M, Taub DD

Abstract

We have recently demonstrated that all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cis RA) promote IL-4, IL-5 and IL-13 synthesis, while decreasing IFN-gamma and TNF-alpha expression by activated human T cells and reduces the synthesis of IL-12p70 from accessory cells. Here, we have demonstrated that the observed effects using ATRA and 9-cis RA are shared with the clinically useful RAR ligand, 13-cis retinoic acid (13-cis RA), and the retinoic acid receptor-alpha (RAR-alpha)-selective agonist, AM580 but not with the RAR-beta/gamma ligand, 4-hydroxyphenylretinamide (4-HPR). The increase in type 2 cytokine production by these retinoids correlated with the expression of the T cell activation markers, CD69 and CD38. The RAR-alpha-selective agonist, AM580 recapitulated all of the T cell activation and type 2 cytokine-inducing effects of ATRA and 9-cis-RA, while the RAR-alpha-selective antagonist, RO 41-5253, inhibited these effects. These results strongly support a role for RAR-alpha engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production.

MeSH Terms
Antigens, CD/biosynthesis Antigens, Differentiation, T-Lymphocyte/biosynthesis Antineoplastic Agents/immunology,pharmacology Benzoates/pharmacology Cell Differentiation/immunology Chromans/pharmacology Cytokines/metabolism Dermatologic Agents/pharmacology Fenretinide/pharmacology Gene Expression Regulation Humans Lectins, C-Type Lymphocyte Activation/drug effects Receptors, Retinoic Acid/agonists,antagonists & inhibitors,immunology,metabolism Retinoic Acid Receptor alpha Tetrahydronaphthalenes/pharmacology Th2 Cells/drug effects,immunology,metabolism Tretinoin/administration & dosage,immunology,metabolism Tumor Cells, Cultured
Chemicals
Antigens, CD Antigens, Differentiation, T-Lymphocyte Antineoplastic Agents Benzoates CD69 antigen Chromans Cytokines Dermatologic Agents Lectins, C-Type RARA protein, human Receptors, Retinoic Acid Retinoic Acid Receptor alpha Tetrahydronaphthalenes Am 580 Ro 41-5253 Fenretinide Tretinoin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Dawson Harry D
Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, MD 21224, USA. harry.dawson@ars.usda.gov
Collins Gary
Pyle Robert
Key Michael
Taub Dennis D
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Article Info
Journal
BMC immunology
Abbr.
BMC Immunol
ISSN
1471-2172
DOI
10.1186/1471-2172-9-16
Email
harry.dawson@ars.usda.gov
Published
2008-04-16
Epub
2008-00-16
Pages
16
Language
English
Region
England
NLM ID
100966980
PMCID
PMC2394516
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1186/1471-2172-9-16 PMC Full Text View journal details
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