Inhibitors of IL-2 production and IL-2 receptor expression in human leukemic T-cell line, Jurkat.
1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a protein kinase inhibitor, suppressed interleukin 2 (IL-2) production and IL-2 receptor (IL-2R) expression of the human leukemic T-cell line, Jurkat, induced by 12-O-tetradecanoyl-phorbol-13-acetate and phytohemagglutinin-P. This effect was significant at 5 microM H-7 without loss of cell viability. Such activity was not observed with N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA 1004), a potent inhibitor of cGMP- and cAMP-dependent kinases, and a weak inhibitor of Ca2+-phospholipid-dependent protein kinase (protein kinase C). These findings suggest that protein kinase C is more closely associated with IL-2 receptor expression and IL-2 production of T cells than cGMP- or cAMP-dependent kinases. In addition, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin inhibitor, suppressed both IL-2 production and IL-2R expression. Cycrosporin A (Cy A), a potent immunosuppressive drug, markedly inhibited IL-2 production of Jurkat cells whereas it did not affect the IL-2R expression. Thus, the mechanism of action of Cy A appears to differ from that of the protein kinase inhibitor, H-7, and the calmodulin inhibitor, W-7.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002460:Cell Line; D003524:Cyclosporins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D007546:Isoquinolines / Q000494:pharmacology; D007945:Leukemia, Lymphoid / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000032:analysis* / Q000187:drug effects; D015375:Receptors, Interleukin-2; D013449:Sulfonamides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003524:Cyclosporins; D007376:Interleukin-2; D007546:Isoquinolines; D010879:Piperazines; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D013449:Sulfonamides; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013755:Tetradecanoylphorbol Acetate