The effect of RU 486 and related compounds on cultured macrophage differentiation and function.
OBJECTIVE
Our purpose was to examine RU 486 and related compounds on macrophage scavenger receptors and cellular adhesion.


METHODS
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.
Roberts
C P
CP
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Murphy
A A
AA
Santanam
N
N
Parthasarathy
S
S
D000975:Antioxidants / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D005453:Fluorescence; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins; D015735:Mifepristone / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation
D000975:Antioxidants; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D015735:Mifepristone; D016912:Levonorgestrel; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate