Brungs M, Rådmark O, Samuelsson B, Steinhilber D
Department of Pharmaceutical Chemistry, University of Tübingen, F.R.G.
Biochem Biophys Res Commun. 1994 Dec 30;205(3):1572-80. doi: 10.1006/bbrc.1994.2846.
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.
血清蛋白转化生长因子β（TGFβ）在二甲基亚砜（DMSO）诱导分化的HL-60细胞中诱导5-脂氧合酶（5-LO）活性，这部分依赖于血清脂质的存在（Steinhilber, D., Hoshiko, S., Grunewald, J., Rådmark, O., and Samuelsson, B. (1993) Biochim. Biophys. Acta 1178, 1-8）。在此我们证明，皮摩尔浓度的1,25-二羟基维生素D3（VD3）可替代血清脂质部分。在存在DMSO和血清蛋白的情况下分化4天后，高浓度的VD3（24 nM）可使完整HL-60细胞的5-LO mRNA诱导增加4倍，5-LO蛋白增加14倍，5-LO活性上调38倍。单独使用VD3也可使5-LO蛋白表达和活性大幅上调。另一方面，单独的TGFβ对5-LO途径的诱导作用较差，需要分化诱导剂（视黄酸、DMSO或VD3）的存在。当VD3和TGFβ联合使用时，在细胞匀浆和完整细胞中观察到5-LO蛋白表达和活性的最显著诱导。
