Activities per year
Abstract
OBJECTIVE: The infl uence of the pregnancy hormone progesterone on
macrophage activation is well studied due to the existence of macrophages
within the female reproductive tract and uterus during pregnancy. The
production of nitric oxide (NO) from L-arginine, occurs via the action of the
enzyme nitric oxide synthase-2 (NOS2) and can be induced experimentally
by LPS. Progesterone downregulates NO production through binding the
glucocorticoid receptor, in order to limit infl ammation. Arginase I also uses
L-arginine as a substrate resulting in the production of L-ornithine and urea as
a by-product. Induction of arginase I is typically associated with stimulation
with the Th2 associated cytokines IL-4 and IL-13. The aim of this work was
to investigate the ability of progesterone to modulate arginase gene expression
and enzyme activity in murine macrophages.
METHOD: Macrophages were grown from the bone marrow of BALB/c
mice for 8-10 days. These cells were then exposed to progesterone (62.5µM)
for approximately 16 hours prior to stimulation with IL-4 (100U/ml), LPS
(200ng/ml) or a combination of both. Expression of argI and nos2 mRNA
transcripts were analysed by quantitative real time PCR. NOS2 activity was
determined by carrying out the Greiss assay on cell supernatants and arginase
activity determined the ability of arginase within cell lysates to produce urea
from L-arginine. Statistical signifi cance of differences was calculated by a
Mann-Whitney U-test and p<0.05 was accepted as signifi cant.
RESULTS: Progesterone downregulates arginase activity in macrophages
stimulated with LPS or in combination with IL-4. By comparison with
norgestrel, a synthetic progestin that binds only the progesterone receptor, and
dexamethasone which binds the glucocorticoid receptor, we demonstrate that
progesterone modulates arginase activity through the glucocorticoid receptor.
In addition, Real Time PCR analysis revealed that progesterone downregulates
IL-4 induced and LPS induced argI gene expression.
CONCLUSION: In addition to limiting NO production, progesterone acts to
limit arginase I gene expression and enzyme activity, possibly as a means of
dampening all forms of macrophage activation.
Original language | English |
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Pages (from-to) | 119A |
Journal | Reproductive Sciences |
Volume | 16 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2009 |
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Dive into the research topics of 'Modulation of macrophage arginase gene expression and activity by progesterone'. Together they form a unique fingerprint.Activities
- 1 Participation in conference
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56th Annual Congress of the Society for Gynecological Investigations
Menzies, F. (Participant)
17 Mar 2009 → 21 Mar 2009Activity: Participating in or organising an event › Participation in conference