The present study compared the role of two protein kinase C (PK-C) activating agents, the phorbol ester phorboI-12-acetate-13-myristate (PMA) and the membrane-permeating diacylglycerol dioctanoyl-sn-glycerol (DiC8) in the activation of EL4i6.1 thymonia cells. These cells have twen shown to express interleukin-2 receptors (IL-2K) upon stimulation with optimal amounts of PMA (1 0 nginil); also, suboptimal drTl(.)UntS of PMA (1 ngirnl) synergized with the C a l i ionophore ionomycin and recombinant interleukin-1 (rlL-1) (Lowenthal et al., l')8h). Comparing PMA and DiC8 Icd to the following results: PMA at 10 ng/mI induced IL-2R; in contrast, DiC8 (30-3 FLgiml) alone was unable to induce IL-2R, although it did synergize with iwomycin (0.5 pginil) and dI.-I. Bihourly additions of DiCO did not change this pattern. The addition of DiCA together with rlL-2 also resulted in no IL-2R expression. Furthermore, DiC8 (10 Fgiml) effecttvely translocated PK-C. Therefore, the dilfercnces observed between PMA and DiC8 do not serm to be due to differences in mctabolism or to an inability to translocate PK-C. Analysis of messenger (m) RNA produced in stirnulated EL4/6.1 cells revealed that DiC8 was also unal-ilv to induce niRNA for IL-2R.
Our data suggest that PMA, especially at "optimal" roncentrations, might have effects that cannol bc mimicked by diacylglycerol. Furthermorc, it seems that the deficient activity of di<icylglycerols can be compensated for by a Ca' ' ionopliore and, depending on the cellular system, by further signals such as IL-1,