Effects of rolipram and CI-930 on IL-2 mRNA transcription in human Jurkat cells

Interleukin-2 (IL-2) is a major mediator of immunologic responses involved in many chronic inflammatory diseases. We have investigated the effects of rolipram, a PDE-IV inhibitor, and CI-930, a PDE-III inhibitor, on IL-2 gene expression in the Jurkat human T cell line. The immunosuppressant cyclospo...

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Bibliographic Details
Published in:Agents and Actions 1993-03, Vol.39 Spec No (S1), p.C89-C92
Main Authors: Lewis, G M, Caccese, R G, Heaslip, R J, Bansbach, C C
Format: Article
Language:English
Subjects:
Animals
Cell Survival
Humans
Interleukin-2 - biosynthesis
Interleukin-2 - genetics
Lymphocyte Activation - drug effects
Mice
Mice, Inbred C57BL
Phosphodiesterase Inhibitors - pharmacology
Pyridazines - pharmacology
Pyrrolidinones - pharmacology
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rolipram
Spleen - cytology
Spleen - drug effects
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
Tetradecanoylphorbol Acetate - pharmacology
Transcription, Genetic - drug effects
Tumor Cells, Cultured
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Summary:Interleukin-2 (IL-2) is a major mediator of immunologic responses involved in many chronic inflammatory diseases. We have investigated the effects of rolipram, a PDE-IV inhibitor, and CI-930, a PDE-III inhibitor, on IL-2 gene expression in the Jurkat human T cell line. The immunosuppressant cyclosporin A (CsA) was included as a positive control. Jurkat cells were stimulated with 1 microgram/ml phytohemagglutinin (PHA) and 50 ng/ml phorbol 12-myristate, 13-acetate (PMA) for 6 h, and mRNA was analyzed using reverse transcription and polymerase chain reaction (RT/PCR). IL-2 transcription was greatly inhibited by 1 microM CsA, whereas neither 10 microM rolipram nor 10 microM CI-930 had any effect on steady-state levels of IL-2 mRNA. Therefore, PDE inhibitors do not affect synthesis of IL-2 mRNA in this model of activated T cells. This is of interest given that these agents inhibit the proliferation of primary T cells. For murine splenocytes stimulated by 2.5 micrograms/ml concanavalin A (Con A), rolipram had an IC50 of 0.09 microM and CI-930 an IC50 of 4.4 microM. These concentrations are below those at which IL-2 mRNA synthesis was shown to be unaffected. Therefore, the mechanism by which inhibitors of PDE-III and PDE-IV affect T cell proliferation is not likely to involve suppression of IL-2 mRNA transcription.
ISSN:0065-4299
1420-908X
DOI:10.1007/BF01972730