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.