Dual effect of phorbol myristate acetate (PMA) on murine thymocyte cultures.
4 beta-phorbol 12-myristate 13-acetate (PMA), a potent tumor promoter, was found to have a dual effect on interleukin 1-(IL 1) stimulated murine thymocyte cultures. In the absence of 2-mercaptoethanol (2-ME) or other sulfhydryl containing compounds, PMA inhibited 3H-thymidine incorporation, while at the same concentrations but in the presence of sulfhydryl agents, PMA exerted a potent stimulatory effect. The other sulfhydryl compounds giving effects resembling 2-ME were dithiothreitol and cysteine, while glutathione and various oxygen radical scavengers (catalase, superoxide dismutase, histidine, alpha-tocopherol or mannitol) had no such effect. 2-ME enhanced the response of thymocytes incubated with PMA even when added 24 h after initiation of the cultures, but not at the 48 h interval. Harvesting the thymocyte cultures at various intervals showed that the inhibitory effect of PMA was already fully pronounced 48 h after initiation of the cultures. On the other hand, the stimulatory effect of PMA on cultures activated with IL 1 in the presence of 2-ME took place mainly during the last 24 h of the 72-h culture period. The modulation of the effect of PMA on thymocyte activation by 2-ME or similar agents may account for the apparent discrepancies in the literature concerning the action of PMA in lymphocyte cultures.
D000818:Animals; D002478:Cells, Cultured; D007375:Interleukin-1 / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008623:Mercaptoethanol / Q000494:pharmacology; D051379:Mice; D010704:Phorbols / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D007375:Interleukin-1; D010704:Phorbols; D013438:Sulfhydryl Compounds; D008623:Mercaptoethanol; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine