IL-6 enhanced the retinoic acid-induced differentiation of human acute promyelocytic leukemia cells

It has been shown that retinoic acid (RA) induced the expression of interleukin-6 (IL-6) in human acute promyelocytic leukemia HL-60 cells. In the present study, we examined the ability of RA to induce the expression of gp130, the signal-transducing receptor component for IL-6, in HL-60 and a RA-supersensitive cell line HL-60/S4. We found that RA induced the expression of gp130, at both the mRNA and protein levels, in HL-60 and HL-60/S4 cells. Interestingly, the induction of gp130 expression observed in the RA-supersensitive HL-60/S4 cells was much more pronounced than that observed in HL-60 cells. Furthermore, activation of the RA-induced gp130 by exogenous IL-6 potentiated the differentiating effects of RA. The synergistic effects observed for IL-6 and RA was also much stronger in HL-60/S4 cells than in HL-60 cells. Our findings suggest that the differentiating effects of RA may partially be mediated by the up-regulation of IL-6/gp130 signaling in HL-60 and HL-60/S4 cells.