Differential effect of cyclosporin A on activation signaling in human T cell lines.
Different T cell lines, which can be induced to secrete interleukin 2 (IL-2) in vitro, were used to dissect the effect of cyclosporin A (CsA). The T leukemia cell Jurkat requires an increase in cytoplasmic calcium concentration ([Ca++]i) and phorbol myristate acetate (PMA) for the induction of IL-2 production, which is completely blocked by CsA. Another T cell line, HUT 78, also produces IL-2 in response to a rise in [Ca++]i and PMA; however, in HUT 78, PMA alone induces low levels of IL-2 production that is not blocked by CsA. After treatment with 5-azacytidine, HUT 78 cells produced maximal levels of IL-2 in response to PMA alone without requiring [Ca++]i increasing stimuli. In these cells no inhibitory effect of CsA on PMA-induced activation could be demonstrated. In addition, CsA does not inhibit PMA-induced translocation of protein kinase C. These data suggest that CsA does not globally inhibit IL-2 gene expression, but rather interferes with signaling events of T cell activation.
Manger
B
B
Hardy
K J
KJ
Weiss
A
A
Stobo
J D
JD
D001374:Azacitidine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002999:Clone Cells; D003524:Cyclosporins / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003524:Cyclosporins; D007376:Interleukin-2; D011493:Protein Kinase C; D001374:Azacitidine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium