SUBSTANCE-P STABILIZES INTERLEUKIN-2 MESSENGER-RNA IN ACTIVATED JURKAT CELLS

We investigated here the mechanism leading to the enhancement of interleukin (IL)-2 mRNA that we described in a previous work when Jurkat cells were co-stimulated with PHA + PMA and 10(-12) M of the Substance P (SP) neuropeptide. We show that the SP-augmented IL-2 mRNA signal is totally abrogated by an early addition of cyclosporin A, actinomycin D or cycloheximide. SP does not affect the IL-2 gene transcription, as evidenced by nuclear run on assays. In contrast, a posttranscriptional alteration of the IL-2 mRNA is shown, by demonstrating that the degradation rate of IL-2 mRNA following the addition of actinomycin D, at 4 h, was delayed in the (PHA + PMA)-activated cell cultures containing 10(-12) M of SP. Thus, the SP-induced augmentation of secreted IL-2 in activated T cells we demonstrated previously must result from an SP increase of the IL-2 mRNA stability.