ENHANCEMENT OF INTERLEUKIN-3-DEPENDENT MAST-CELL PROLIFERATION BY SUPPRESSION OF C-JUN EXPRESSION

We have previously shown that protein kinase C (PKC) depletion is asso ciated with an increase in the proliferation of interleukin 3 (IL-3)-i nduced mast cells. Here we show that the AP-1 components c-Jun and c-F os are induced by IL-3. While c-Jun's induction by IL-3 is totally dep endent on PKC, c-Fos induction by IL-3 is only attenuated by PKC deple tion. AP-1 binding activity was also induced by IL-3 but this inductio n was PKC independent. These results indicated a possible involvement of c-Jun in the inhibition of IL-3-induced growth regulation. A suppor t for this assumption came from experiments in which an increase in th ymidine incorporation into mast cells was noted when c-jun antisense o ligomers were administered to IL-3-treated cells. Since the only known effect of direct inhibition of c-Jun on proliferation rates in severa l cellular systems was a reduction of proliferation, we verified that our c-jun antisense oligomer could also inhibit proliferation rates in fibroblasts where such a repression was previously reported. Thus c-J un has an inhibitory effect on IL-3 induction of mast cells proliferat ion that is distinct from its role in several other cellular environme nts. These observations reveal the involvement of AP-1 and its compone nts in IL-3-induced signal transduction and the importance of the mast cell environment in determining their specific cellular function.