The Presence Of Prostaglandin E2 In Decidua

The Presence Of Prostaglandin E2 In Decidua

1. The mechanism by which prostaglandin E2 (PGE2) inhibits human T-lymphocyte activation
was studied. Analysis of physiological concentrations of PGE2 on interleukin-2 (IL-2)
production, expression of IL-2 receptor (TAC antigen) and expression of transferrin
receptor after in vitro activation with phytohaemagglutinin. PGE2 inhibited T lymphocyte
proliferation by 80-90% of control values. This was associated with a similar degree of
inhibition of IL-2 production while the expression of IL-2 receptor was not affected. In
marked contrast to the expression of transferrin receptor which was inhibited 65% after 72
hours if in vitro activation (1).
These studies demonstrated that PGE2 exerts its inhibitory effect on T cell activation and
proliferation via two distinct pathways: inhibition of IL-2 production and inhibition of
transferrin receptor expression. The transferrin receptor expression is mediated via the
cAMP pathway and is IL-2 independent (1).


2. Since pregnancy impairs neither the primary or the secondary response of the mother
against a heterotopic allograft the paternal or fetal allotype, the protective mechanism must
be sought locally at the feto maternal interface. Early decidual stroma cells seem to
represent an important suppressor cell class in the early gestation decidua. The major cell
class of mediator molecules was identified as prostaglandin E2 on the basis of the following
results (a) the presence of indomethacin (10 5M) or varying dilutions of an anti-PGE2
antibody abrogated this suppression substantially or completely. (b) the addition of pure
PGE2 (3 x 10-7 to 1.1 x 10 5M) but not PGF2H$6*76:+1(*+$4$+:0*-dependent suppressor
effect. (c) PGE2 levels measured in the day 4 of the mixed lymphocyte cultured cells
containing decidual cells were positively correlated with the decidual cell dose or the
degree of suppression.


Menstrual Age (from LMP in weeks)

PGE2 concn in the culture ng/ml decidual tissue

7.5

30.7

8.5

35.9

8.5

52.8

10.5

20.4

12.0

25.1

 

2. A strong dose dependent suppressor activity was exhibited by Ficoll-Paque separated nucleated cell preparations having a high incidence (70-94%) of typical decidual stroma cells at 6.5-9.5 weeks from LMP (2).

3. At the fetal maternal interface the physiological level of PGE2 primarily secreted by decidual cells might be higher than 10-8nanograms/ml. Macrophages secrete large amounts of IL-1 and PGE2 (3).


4. The authors have previously shown that prostaglandin (PGE2) produced in abundance by decidual stroma cells, now show that prostaglandin E2 promotes the migration of first trimester human extra villous trophoblast (EVT) by increasing the cellular concentration of calcium and activating calpacin, furthermore CD42 silencing using sirna inhibited PGE2 migration of HTR-8/SV neo cells (EVT cell line) (4).


5. Conclusion. In this study we demonstrate that the inflammatory response induced by antiprogesterone in combination with prostaglandin E2 analogue is accomplished by both increases in macrophages and neutrophils numbers and decreases in progesterone receptors (PR) and estrogen receptor A (ERA) (5).

REFERENCES

1. CHAUAIB S, WELTE K, MERTELSMANN R, DUPONT B
Prostaglandin E2 acts at two distinct pathways of T-lymphocyte activation. Inhibition of interleukin-2 production and down-regulation of transferrin receptor expression.
J. Immunol. 1985;135(2):1172-1179.


2. PARHAR R S, KENNEDY T G, LALA P K
Suppression of lymphocyte alloreactivity by early gestational human decidua: characterisation of suppressor cells and suppressor molecules.
Cell Immunical. 1988;116:392-410.


3. TAGEL S, LALA P K, POWELL W A, CASPER L F
Interleukin-1 stimulates human chorionic gonadotrophin secreted by first trimester human trophoblast.
J Clin. Endocrinol. Metab. 1989;68:992-995.


4. NICOLA C, LALA P K, CHAKRABORTY C
Prostaglandin E2 medicated migration of human trophoblast requires RAC 1 and CD42.
Biol. Reprod. 2008;78(5):976-982.


5. MILNE S A, HENDERSON T A, KELLY R W, SAUNDERS P T, BAIRD D T, CRITCHLEY O D
Receptor expression in human first trimester decidua: Regulation by antiprogesterone progesterone E analogue.
Journal Clinical Endocrinology and Metabolism 2005;90(7):4315-4321.

 

 

85%

85% of pregnant women have two episodes of nausea per day.

70-80%

Nausea & vomiting in pregnancy (NVP) is very common, on average it affects 70-80% of pregnant women to a greater or lesser extent.

30%

30% of pregnant women in paid employment need time off work due to NVP.

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