On the induction of 5-lipoxygenase expression and activity in HL-60 cells: effects of vitamin D3, retinoic acid, DMSO and TGF beta.

Induction of 5-LO activity in DMSO differentiated HL-60 cells, by the serum protein TGF beta, was partially dependent on the presence of serum lipids (Steinhilber, D., Hoshiko, S., Grunewald, J., Rådmark, O., and Samuelsson, B. (1993) Biochim. Biophys. Acta 1178, 1-8). Here we demonstrate that the serum lipid fraction can be substituted by picomolar concentrations of 1,25-dihydroxyvitamin D3 (VD3). A high concentration of VD3 (24 nM) gave a 4-fold induction of 5-LO mRNA, a 14-fold increase in 5-LO protein, and a 38-fold upregulation of the 5-LO activity of intact HL-60 cells after differentiation in the presence of DMSO and serum proteins for 4 days. Also VD3 alone gave a substantial upregulation of 5-LO protein expression and activity. On the other hand, TGF beta alone was a poor inducer of the 5-LO pathway, the presence of a differentiation inducer (retinoic acid, DMSO or VD3) was required. The most prominent induction of 5-LO protein expression and activity in cell homogenates and intact cells was observed when VD3 and TGF beta were combined.