Phorbol myristate acetate induces IL-2 secretion by HUT 78 cells by a mechanism independent of protein kinase C translocation.
The protein kinase C (PKC) inhibitor H-7 was used to study the role of PKC in IL-2 secretion. In Jurkat E6.1, a phenotypically non-activated human T-cell line, IL-2 secretion in response to a combination of PMA and the calcium ionophore, ionomycin, or to the mitogen phytohaemagglutinin (PHA) was completely inhibited by H-7. In contrast, HUT-78, a phenotypically activated T-cell line, secreted IL-2 in response to PMA alone, and IL-2 secretion was not inhibited by doses of H-7 that completely blocked PKC activity. We conclude that PMA can stimulate IL-2 secretion independent of the translocation of PKC activity, and suggest that there is an alternative mechanism of action for phorbol esters in activated T cells.
Kelleher
D
D
Department of Medicine, University of California, San Diego, La Jolla 92093.
Pandol
S J
SJ
Kagnoff
M F
MF
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002460:Cell Line; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D007546:Isoquinolines / Q000494:pharmacology*; D008223:Lymphoma / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007376:Interleukin-2; D007546:Isoquinolines; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate