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

Abstract

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 1μg/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 μM CsA, whereas neither 10 μM rolipram nor 10 μM 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 μg/ml concanavalin A (Con A), rolipram had an IC₅₀ of 0.09 μM and CI-930 an IC₅₀ of 4.4 μM. 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.