Thapsigargin induces IL-2 receptor α-chain in human peripheral and Jurkat T cells via a protein kinase C-independent mechanism

Abstract

Thapsigargin (TG), an inhibitor of Ca 2+-ATPase, depletes intracellular Ca 2+ stores and induces a sustained Ca 2+ influx without altering phosphatidyl inositol levels. TG plus phorbol myristate acetate (PMA) but not TG alone induced IL-2 in Jurkat T cells, suggesting that TG had no effect on protein kinase C (PKC). However, TG induced increases in IL-2Rα protein as well as IL-2Rα mRNA in Jurkat T cells in a dose-dependent manner. A similar increase in IL-2Rα by TG was also observed in human peripheral T cells. Further, like PMA, TG markedly induced NFκB in Jurkat T cells. However, TG and PMA exhibited a synergistic action on IL-2Rα expression, suggesting that TG and PMA induce IL-2Rα through distinct pathways. PMA- but not TG-induced IL-2Rα is inhibited by the PKC inhibitor H7, whereas TG- but not PMA-induced IL-2Rα was inhibited by cholera toxin, forskolin and 1,9-dideoxy forskolin. In toto, these results suggest that TG induces IL-2Rα in human T cells through a PKC-independent pathway.