Cyclosporin A suppresses the expression of the interleukin 2 gene by inhibiting the binding of lymphocyte-specific factors to the IL-2 enhancer

C Randak; T Brabletz; M Hergenröther; I Sobotta; E Serfling

doi:10.1002/j.1460-2075.1990.tb07433.x

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Cyclosporin A suppresses the expression of the interleukin 2 gene by inhibiting the binding of lymphocyte-specific factors to the IL-2 enhancer

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Cyclosporin A suppresses the expression of the interleukin 2 gene by inhibiting the binding of lymphocyte-specific factors to the IL-2 enhancer

C Randak, T Brabletz, M Hergenröther, I Sobotta and E Serfling

The EMBO journal, Vol.9(8), pp.2529-2536

08/1990

DOI: 10.1002/j.1460-2075.1990.tb07433.x

PMCID: PMC552283

PMID: 2369902

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Abstract

Cyclosporin A (CsA), a powerful immunosuppressive drug, inhibits the synthesis of lymphokines in T lymphocytes at the level of gene transcription. Using protein extracts from El4 lymphoma cells we show that the binding of lymphocyte-specific factors interacting with the two so-called purine boxes (Pu-boxes) of the interleukin 2 (IL-2) enhancer are missing in CsA-treated cells. The CsA-sensitive factors are newly synthesized upon induction. The most prominent factor consists of 45 kd polypeptides and contacts both Pu-boxes at the two central G residues within the identical core sequence AAGAGGAAAA. The CsA-mediated suppression of factor binding to the Pu-boxes correlates well with functional studies in which the inducible, T cell-restricted proto-enhancer activity of Pu-boxes was selectively repressed by CsA. These observations support the conclusion that the suppression of factor binding to the Pu-boxes by CsA impairs the activity of IL-2 and of further lymphokine genes, thereby inhibiting the synthesis of lymphokines in T lymphocytes.

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Title: Subtitle: Cyclosporin A suppresses the expression of the interleukin 2 gene by inhibiting the binding of lymphocyte-specific factors to the IL-2 enhancer
Creators: C Randak - Institut für Virologie und Immunbiologie, Universität Würzburg, FRG
T Brabletz - Institut für Virologie und Immunbiologie, Universität Würzburg, FRG
M Hergenröther - Institut für Virologie und Immunbiologie, Universität Würzburg, FRG
I Sobotta - Institut für Virologie und Immunbiologie, Universität Würzburg, FRG
E Serfling - Institut für Virologie und Immunbiologie, Universität Würzburg, FRG
Resource Type: Journal article
Publication Details: The EMBO journal, Vol.9(8), pp.2529-2536
DOI: 10.1002/j.1460-2075.1990.tb07433.x
PMID: 2369902
PMCID: PMC552283
ISSN: 0261-4189
eISSN: 1460-2075
Language: English
Date published: 08/1990
Academic Unit: Pulmonary Medicine; Stead Family Department of Pediatrics
Record Identifier: 9984093491702771

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