Substance P stabilizes interleukin-2 mRNA 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.
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Laboratoire d'Immunologie Cellulaire et de Transplantation, CNRS Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
D002460:Cell Line; D004355:Drug Stability; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D008213:Lymphocyte Activation; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000378:metabolism*
D007376:Interleukin-2; D012333:RNA, Messenger; D013373:Substance P