Enhancement of perforin by retinoic acid is mediated by protein kinase C.

We previously demonstrated that interleukin-2 induced murine lymphokine-activated killer cell activity is augmented by retinoic acid. The enhanced cytotoxicity is significantly correlated with the increase in PKC. In the present study, we have shown that retinoic acid increases the expression of perforin, a potent cytolytic mediator, at both protein and mRNA levels. This enhancement can be induced by a direct stimulation of PKC signaling pathway, as manipulated by a short term incubation of lymphokine-activated killer cells with 12-O-tetradecanoyl-phorbol-13-acetate and ionomycin, and suppressed by PKC inhibitors. These results suggest that PKC plays a regulatory role in the enhancement of the expression of cytolytic mediators in retinoic acid-augmented lymphokine-activated killer cells.