Antisense cyclic adenosine 5'-monophosphate response element modulator up-regulates IL-2 in T cells from patients with systemic lupus erythematosus.
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.
Tenbrock
Klaus
K
Department of Cellular Injury, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Juang
Yuang-Taung
YT
Gourley
Mark F
MF
Nambiar
Madhusoodana P
MP
Tsokos
George C
GC
D000328:Adult; D000242:Cyclic AMP / Q000502:physiology*; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012097:Repressor Proteins; D020218:Response Elements / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology; D014162:Transfection; D015854:Up-Regulation / Q000276:immunology*
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP