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Production in Activated Mouse Macrophages by Progesterone1
,*
Departments of
*
Anatomy and Cell Biology and
Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160
The purpose of this study was to investigate the relationships
between macrophage production of TNF-
and female hormones. Northern
blot hybridization experiments showed that the female sex steroid
hormone, progesterone, decreases steady state levels of TNF- mRNA in
LPS-activated mouse macrophages (RAW 264.7 and ANA-1 cells) in vitro.
The production of intracellular and secreted TNF- protein, as
determined by ELISA, was decreased in both progesterone- and
dexamethasone-treated, LPS-stimulated macrophages. Estrogen had no
effect on expression of the TNF- gene in mouse macrophages and did
not alter progesterone-mediated suppression. Additional experiments
conducted to investigate the mechanism of action of progesterone showed
that this hormone, like dexamethasone, elevates steady state mRNA
levels of I
B and increases the levels of IB protein that
are translocated from the cytoplasm to the nucleus. Thus, progesterone
is a potent inhibitor of steady state levels TNF- mRNA and TNF-
protein production in activated macrophages and may achieve this result
through effects on an inhibitor of NF-B.
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