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

Roberts CP, C P Roberts, A A Murphy, Murphy AA, N Santanam, Nalini Santanam, Parthasarathy S, S Parthasarathy
American Journal of Obstetrics and Gynecology · 1996 · vol. 175(2) , pp. 248–259 · doi:10.1016/s0002-9378(96)70132-1 · PMID:8765239 · W2039150269
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This study investigated the impact of RU 486 and related compounds on the differentiation and function of cultured macrophages.

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Abstract

ObjectiveOur purpose was to examine RU 486 and related compounds on macrophage scavenger receptors and cellular adhesion.Study designTHP-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.ResultsBoth 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.ConclusionsRU 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.

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MeSH descriptors

Macrophages Macrophages Membrane Proteins Mifepristone Receptors, Lipoprotein Antioxidants Antioxidants Cell Adhesion Cell Adhesion Cell Count Cell Count Cell Differentiation Cell Differentiation Cell Line Dexamethasone Dexamethasone Fluorescence Humans Levonorgestrel Levonorgestrel

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