Sequential induction of 5-lipoxygenase gene expression and activity in Mono Mac 6 cells by transforming growth factor beta and 1,25-dihydroxyvitamin D3

Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):107-11. doi: 10.1073/pnas.92.1.107.


5-Lipoxygenase (5-LO; EC activity in the human monocytic cell line Mono Mac 6 was upregulated by combined treatment with transforming growth factor beta 1 (TGF-beta) and 1,25-dihydroxyvitamin D3 (VD3). In undifferentiated cells, 5-LO enzyme activity was undetectable. After the addition of TGF-beta plus VD3, the activity of intact cells was 800 ng per 10(6) cells--500 times more than the assay detection limit. Also 5-LO protein and mRNA expression were induced > 128-fold and 64-fold, respectively, as compared to undifferentiated cells. Both TGF-beta and VD3 were required for these prominent responses. Either agent alone gave small amounts of 5-LO protein and mRNA but very low 5-LO activities. After the addition of TGF-beta and VD3, the induction of 5-LO protein was obvious after 1 day, but the increase in activity was delayed and did not appear until the second day. Pretreatment of cells with TGF-beta or VD3 alone for 2 days led to 5-LO protein expression but very low enzyme activity. Addition of the lacking second inducer was required for full induction of 5-LO protein expression and for upregulation of enzyme activity. Partial purification of 5-LO from Mono Mac 6 cells and recombination with soluble cellular proteins from different sources indicated the presence of cytosolic factors that affect the activity of 5-LO.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 5-Lipoxygenase / biosynthesis*
  • Arachidonate 5-Lipoxygenase / isolation & purification
  • Base Sequence
  • Cell Differentiation
  • Cell Line
  • Cholecalciferol / pharmacology*
  • Chromatography, Affinity
  • DNA Primers
  • Drug Interactions
  • Enzyme Induction / drug effects
  • Gene Expression / drug effects*
  • Humans
  • Kinetics
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Time Factors
  • Transforming Growth Factor beta / pharmacology*


  • DNA Primers
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Cholecalciferol
  • Arachidonate 5-Lipoxygenase