Interleukin 4-induced proliferation in normal human keratinocytes is associated with c-myc gene expression and inhibited by genistein

Abstract

We studied the effect of IL-4 on the proliferation of cultured normal human keratinocytes. Keratinocyte proliferation was stimulated by IL-4 and inhibited by anti-IL-4 antibody in a concentration-dependent manner, Anti-IL-6 antibody did not inhibit normal human keratinocyte proliferation, suggesting that the IL-4 could directly induce proliferation of these cells, IL-4 significantly induced cell cycle G(0)/G(1) to S phase progression, The keratinocyte proliferation by IL-4 was mediated through one of the growth control genes, c-myc protooncogene. The expression of c-myc mRNA was significantly increased after IL-4 treatment of the keratinocytes, suggesting that c-myr: plays a key role in the control of proliferation, The signal transduction pathways induced by IL-4 in the keratinocytes were studied with inhibitors of signal transduction. Genistein, a tyrosine kinase inhibitor, suppressed the level of the induced c-myc mRNA expression, but H7, a serine/threonine kinase inhibitor, and okadaic acid, a protein phosphatase 1 and 2A inhibitor, did not block the induced c-myr: gene expression, Taken together, these results suggest that IL-4 stimulates the proliferation of keratinocytes in vitro by promoting a transition from G(0)/G(1) to S phase of the cell cycle, Induction of c-myc after IL-4 treatment could indicate an important role for c-myc in the proliferation of keratinocytes. Our observations also suggest that tyrosine kinases may be involved in IL-4-induced proliferation.