Abstract
The cAMP response element modulator (CREM) has been shown to bind specifically to the -180 site of the IL-2 promoter in vitro. CREM protein is increased in T cells of patients with systemic lupus erythematosus (SLE), and it has been considered responsible for the decreased production of IL-2. In this work we show that transcriptional up-regulation is responsible for the increased CREM protein levels and that CREM binds to the IL-2 promoter in live SLE T cells. Suppression of the expression of CREM mRNA and protein by an antisense CREM plasmid, which was force expressed in SLE T cells by electroporation, resulted in decreased CREM protein binding to the IL-2 promoter and increased expression of IL-2 mRNA and protein. Our data demonstrate that antisense constructs can be used to effectively eliminate the expression of a transcriptional repressor. This approach can be used therapeutically in conditions where increased production of IL-2 is desired.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Cyclic AMP / physiology*
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Cyclic AMP Response Element Modulator
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Down-Regulation / immunology
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Female
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Humans
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Interleukin-2 / biosynthesis*
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Interleukin-2 / genetics
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Interleukin-2 / metabolism
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Lupus Erythematosus, Systemic / genetics
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Lupus Erythematosus, Systemic / immunology*
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Male
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Middle Aged
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Oligonucleotides, Antisense / pharmacology*
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Promoter Regions, Genetic / immunology
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Protein Binding / genetics
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Protein Binding / immunology
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RNA, Messenger / antagonists & inhibitors
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RNA, Messenger / biosynthesis
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Repressor Proteins*
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Response Elements / physiology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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Transcription, Genetic / immunology
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Transfection
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Up-Regulation / immunology*
Substances
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DNA-Binding Proteins
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Interleukin-2
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Oligonucleotides, Antisense
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RNA, Messenger
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Repressor Proteins
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Cyclic AMP Response Element Modulator
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Cyclic AMP