An NF-χB-like element plays an essential role in interleukin-1-mediated costimulation of the mouse interleukin-2 promoter
| Autor: | Edgar Serfling, Werner Falk, Kirstin Strieker, Peter H. Krammer |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Interleukin 2
Nuclear Proteins/physiology Interleukin-2/genetics T-Lymphocytes T cell Molecular Sequence Data Immunology 610 Medizin NF-kappa B/physiology In Vitro Techniques Biology Transcription Factors/physiology medicine.disease_cause DNA-Binding Proteins/physiology Mice T-Lymphocytes/physiology Consensus Sequence Gene expression Tumor Cells Cultured medicine Animals Immunology and Allergy Promoter Regions Genetic Receptor Transcription factor ddc:610 Mutation Binding Sites Base Sequence NF-kappa B Nuclear Proteins Interleukin Molecular biology DNA-Binding Proteins medicine.anatomical_structure Gene Expression Regulation Cell culture Interleukin-2 Interleukin-1/physiology Interleukin-1 Transcription Factors medicine.drug |
| Zdroj: | European Journal of Immunology. 23:1475-1480 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.1830230712 |
| Popis: | Interleukin-1 (IL-1) costimulation is required for efficient IL-2 synthesis and IL-2 receptor (IL-2R) expression of T cells. The molecular events leading to these effects are largely unknown. We utilized an IL-1-responsive and an IL-1-non-responsive subclone of the mouse thymoma cell line EL4 to investigate how IL-1 activates IL-2 gene expression. We correlated IL-2 promoter activity with the activity of the endogenous IL-2 gene, thereby showing the biological significance of our results. Our experiments provide new functional data showing that a major target of IL-1 mediated costimulation is the chi B-like site, T cell element distal TCEd (GGGATTTCAC), of the IL-2 promoter. Thus, deletion or mutation of TCEd within a complete IL-2 promoter abrogated IL-1 costimulation in the IL-1 responsive EL4 subclone. Therefore, the TCEd element is functionally essential for the effect of IL-1. We also identified a nuclear factor (NF), IL-1 NF, that binds to the TCEd site after IL-1 stimulation. This factor was only present in the IL-1-responsive EL4 subclone and not in the IL-1-non-responsive subclone after IL-1 stimulation and did not appear after phytohemagglutinin (PHA)-treatment. Binding of IL-1 NF to the TCEd site was competed by a typical chi B oligonucleotide, suggesting that it is similar to NF-chi B in its DNA-binding properties. However, the TCEd element was only activated by costimulation with PHA and IL-1 whereas a typical chi B element was already activated by IL-1 alone. These data suggest that the biological function of the TCEd element of the IL-2 promoter differs from that of a canonical chi B element. Our data provide new evidence that IL-1 acts on the IL-2 promoter by activating the TCEd element via the transcription factor IL-1 NF. Furthermore, activation of this element requires two signals, delivered by IL-1 and PHA, in this way reflecting the activation requirement for the endogenous IL-2 gene. |
| Databáze: | OpenAIRE |
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