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Prostaglandin E2 and other cyclic AMP-elevating agents modulate IL-2 and IL-2R alpha gene expression at multiple
E D Anastassiou1, F Paliogianni, J P Balow
1Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Journal of Immunology (Baltimore, Md. : 1950)
|May 1, 1992
Summary
Cyclic adenosine monophosphate (cAMP) inhibits T cell activation by suppressing IL-2 production and expression. This inhibition occurs at both transcriptional and post-transcriptional levels, involving protein kinase A.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- Cyclic adenosine monophosphate (cAMP) acts as an intracellular second messenger.
- cAMP signaling is known to inhibit T cell activation, proliferation, and interleukin-2 (IL-2) production.
Purpose of the Study:
- To elucidate the precise mechanisms by which cAMP inhibits T cell activation and IL-2 related gene expression.
Main Methods:
- Human peripheral blood T lymphocytes were stimulated using various agents (anti-CD3 mAb, PHA, PMA, ionomycin).
- cAMP levels were elevated using PGE2, cholera toxin, or 8-bromo-cAMP.
- Tyrosine phosphorylation, IL-2 and IL-2R alpha expression (protein and mRNA), and gene transcription were analyzed.
- Nuclear run-off assays and protein kinase A inhibition (H-8) were employed.
Main Results:
- Elevated cAMP inhibited the tyrosine phosphorylation of a 100 kDa protein.
- cAMP significantly decreased IL-2 and IL-2R alpha expression at both protein and mRNA levels.
- Inhibition of IL-2 and IL-2R alpha gene expression by cAMP was mediated at the transcriptional level, involving protein kinase A activation.
- cAMP also reduced the half-life (t1/2) of IL-2 mRNA post-transcriptionally.
Conclusions:
- cAMP exerts inhibitory effects on T cell activation through multiple mechanisms, affecting cellular events from the cell membrane to the nucleus.
- These findings highlight the complex role of cAMP in regulating lymphocyte function and T cell responses.