The effect of RU 486 and related compounds on cultured macrophage differentiation and function

Am J Obstet Gynecol. 1996 Aug;175(2):248-57; discussion 257-9. doi: 10.1016/s0002-9378(96)70132-1.

Abstract

Objective: Our purpose was to examine RU 486 and related compounds on macrophage scavenger receptors and cellular adhesion.

Study design: THP-1 cells were activated with phorbol myristate acetate and treated with dexamethasone, levonorgestrel, and RU 486 alone or in combination. Scavenger receptor activity was determined by counting adhered cells. In addition, fluorescently labeled acetyl low density lipoprotein uptake was determined.

Results: Both dexamethasone and RU 486 significantly decreased activated macrophages (81% and 26% of control). Levonorgestrel stimulated adherent cells in activated monocytes (130% of control). RU 486 and dexamethasone were antagonistic when combined (p < 0.001). In contrast, dexamethasone could not overcome the stimulatory effect of levonorgestrel (p < 0.001). Fluorescent studies yielded similar results.

Conclusions: RU 486 is a known antiglucocorticoid with novel antioxidant properties. Levonorgestrel has antiglucocorticoid but no antioxidant activity. Glucocorticoids decrease scavenger receptors and antioxidants regulate inflammatory cytokines. RU 486 antagonized the inhibitory effect of dexamethasone on scavenger receptors, whereas levonorgestrel was stimulatory. It is therapeutically important to up-regulate scavenger receptor activity by antiglucocorticoids in the peritoneal cavity of women with endometriosis. However, because these mechanisms also induce inflammatory cytokines, a balance of antioxidants and antiglucocorticoids may prove beneficial.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology
  • Cell Adhesion / drug effects
  • Cell Count / drug effects
  • Cell Differentiation / drug effects
  • Cell Line
  • Dexamethasone / pharmacology
  • Fluorescence
  • Humans
  • Levonorgestrel / pharmacology
  • Macrophages / cytology*
  • Macrophages / drug effects
  • Macrophages / physiology*
  • Membrane Proteins*
  • Mifepristone / pharmacology*
  • Receptors, Immunologic / metabolism
  • Receptors, Lipoprotein*
  • Receptors, Scavenger
  • Scavenger Receptors, Class B
  • Tetradecanoylphorbol Acetate / pharmacology
  • Up-Regulation

Substances

  • Antioxidants
  • Membrane Proteins
  • Receptors, Immunologic
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Mifepristone
  • Levonorgestrel
  • Dexamethasone
  • Tetradecanoylphorbol Acetate