Dexamethasone increases expression of 5-lipoxygenase and its activating protein in human monocytes and THP-1 cells

Eur J Biochem. 1997 May 15;246(1):112-8. doi: 10.1111/j.1432-1033.1997.00112.x.


The aim of this study was to assess the effect of dexamethasone on 5-lipoxygenase pathway expression in human peripheral blood monocytes and the acute monocytic leukemia cell line, THP-1. Cells were conditioned over a period of days with dexamethasone, at concentrations relevant in vivo, to study the effect of the glucocorticoid on calcium-ionophore-stimulated 5-lipoxygenase product and arachidonic acid release. The effect of dexamethasone on levels of immunoreactive protein and steady-state messenger RNA encoding for 5-lipoxygenase and its activating protein (5-LAP) was also assessed. Dexamethasone increased the stimulated release of 5-lipoxygenase products from both monocytes and THP-1 cells in a dose-dependent fashion. The increase in product generation was not due to changes in the availability of arachidonic acid. However, immunoreactive protein and steady-state messenger RNA encoding for 5-lipoxygenase and 5-LAP were increased by conditioning with dexamethasone. There was no apparent effect of the glucocorticoid on LTA4-hydrolase-immunoreactive protein levels or specific activity. We conclude that dexamethasone increases 5-lipoxygenase pathway expression in both monocytes and in THP-1 cells. This effect is due, at least in part, to increases in immunoreactive protein and steady-state messenger RNA encoding for 5-lipoxygenase and 5-LAP. These results suggest a role for glucocorticoids in the regulation of 5-lipoxygenase pathway expression in mononuclear phagocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5-Lipoxygenase-Activating Proteins
  • Arachidonate 5-Lipoxygenase / genetics
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Arachidonic Acid / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Dexamethasone / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Epoxide Hydrolases / metabolism
  • Gene Expression Regulation / genetics
  • Humans
  • Immunoblotting
  • Indomethacin / pharmacology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Cells, Cultured


  • 5-Lipoxygenase-Activating Proteins
  • ALOX5AP protein, human
  • Carrier Proteins
  • Membrane Proteins
  • RNA, Messenger
  • Arachidonic Acid
  • Dexamethasone
  • Arachidonate 5-Lipoxygenase
  • Epoxide Hydrolases
  • leukotriene A4 hydrolase
  • Indomethacin