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Calcium-dependent Activation of Interleukin-21 Gene Expression in T Cells

Authors
 Hyoung-Pyo Kim  ;  Lisa L. Korn  ;  Warren J. Leonard  ;  Ana M. Gamero 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.280(26) : 25291-25297, 2005 
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN
 0021-9258 
Issue Date
2005
MeSH
Animals ; Base Sequence ; Binding Sites ; CD4 Antigens/biosynthesis ; Calcium/metabolism* ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; Cyclosporine/metabolism ; Cyclosporine/pharmacology ; DNA-Binding Proteins/metabolism ; Deoxyribonuclease I/metabolism ; Gene Expression Regulation ; Humans ; Immunosuppressive Agents/pharmacology ; Interleukin-2/metabolism ; Interleukins/biosynthesis* ; Ionophores/metabolism ; Luciferases/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Genetic ; Molecular Sequence Data ; NFATC Transcription Factors ; Nuclear Proteins/metabolism ; Promoter Regions, Genetic ; Protein Binding ; RNA/metabolism ; Receptors, Antigen, T-Cell/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Nucleic Acid ; Species Specificity ; T-Lymphocytes/metabolism* ; Tacrolimus/pharmacology ; Transcription Factors/metabolism ; Transcription, Genetic
Keywords
15879595
Abstract
Interleukin (IL)-21 is a gamma(c)-dependent cytokine produced by activated T cells with important actions for T, B, and NK cells. The IL-21 gene is adjacent to the IL-2 gene, and like IL-2, IL-21 is strongly induced at the transcriptional level after T cell activation. Interestingly, however, in contrast to the IL-2 gene, a calcium ionophore alone was sufficient to induce IL-21 gene expression in preactivated T cells. Two DNase I hypersensitivity sites were found in the IL-21 gene, corresponding to nucleotide sequences that are conserved in humans and mice. One site is located at the IL-21 promoter region and conferred T cell receptor-mediated IL-21 gene transcription. TCR-induced IL-21 gene expression was inhibited by cyclosporin A and FK506. Correspondingly, the IL-21 5'-regulatory region contains three NFAT binding sites, and induction of IL-21 promoter activity was impaired when these sites were mutated or following treatment with cyclosporin A. Thus, our studies reveal that in contrast to IL-2, a calcium signal alone is sufficient to mediate induction of the IL-21 in preactivated T lymphocytes and that this induction appears to result from specific NFAT binding.
Files in This Item:
T200504624.pdf Download
DOI
10.1074/jbc.M501459200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyoung Pyo(김형표) ORCID logo https://orcid.org/0000-0003-1441-8822
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114964
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