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Role of ETS1 in IL-2 gene expression
V Romano-Spica1, P Georgiou, H Suzuki
1Laboratory of Molecular Oncology, National Cancer Institute, Frederick, MD 21702.
Journal of Immunology (Baltimore, Md. : 1950)
|March 15, 1995
Summary
The ETS1 gene may suppress Interleukin-2 (IL-2) production in T cells. Blocking ETS1 increased IL-2 gene transcription, suggesting ETS1 acts as a negative regulator.
Area of Science:
- Molecular Biology
- Immunology
- Gene Regulation
Background:
- The ETS1 gene encodes a transcription factor that binds to specific DNA sequences.
- ETS1 is highly expressed in resting T cells and decreases upon activation, suggesting a suppressive role in T cell activation.
Purpose of the Study:
- To investigate whether ETS1 regulates the expression of the Interleukin-2 (IL-2) gene.
- To determine the mechanism by which ETS1 might influence IL-2 production.
Main Methods:
- Ectopic expression of antisense (AS) ETS1 in Jurkat T cells to inhibit ETS1 protein formation.
- Assessing IL-2 production and IL-2 promoter activity using reporter gene assays.
- Investigating the effect of cyclosporin A and FK590 on IL-2 production in AS ETS1 transfectants.
Main Results:
- AS ETS1 transfectants showed significantly higher IL-2 production compared to sense ETS1 transfectants.
- Expression of the ETS1 DNA binding domain reduced IL-2 production.
- Increased IL-2 production in AS ETS1 transfectants was linked to enhanced IL-2 gene transcription.
- Cyclosporin A and FK590 completely inhibited IL-2 formation in AS ETS1 transfectants.
Conclusions:
- ETS1 appears to function as a negative regulator of IL-2 gene transcription.
- These findings suggest a potential strategy for engineering endogenous IL-2 expression in T cells.