Prostaglandin E2 Regulates Both lnterleukin-2: DISCUSSION(6)


Overall, data presented here suggest that PGE2 can have diverse effects that depend on exposure time, conditions of stimulation, and PGE2 concentrations. This regulation is specific to PGE2 since PGF2a, another PG synthesized by the bovine embryo and endometrium, could not induce the same effects even though it has the potential to generate similar intracellular messengers. The tremendous increase in GM-CSF mRNAs following PGE2 removal is in agreement with previous findings obtained using human PBL. buy ortho tri-cyclen

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Prostaglandin E2 Regulates Both lnterleukin-2: DISCUSSION(5)

Among probable roles of lymphocyte GM-CSF, sustenance of conceptus growth, regulation of the functions of fellow immune cells like macrophages or NK cells, and reorientation of the local cytokine network have been proposed. Indeed, GM-CSF has been shown to stimulate IL-10 production in a choriocarcinoma cell line and in human lymphocytes (unpublished results), giving support to the hypothesis of a T-helper-2 bias during early pregnancy. Given that uterine epithelial cells also produce GM-CSF during pregnancy, the relative contribution of immune versus nonimmune cells to these biological effects of GM-CSF is yet a matter of speculation. Buy Asthma Inhalers Online

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Prostaglandin E2 Regulates Both lnterleukin-2: DISCUSSION(4)


Results obtained in direct-treatment protocols are believed to mimic the sudden in vivo exposure of endometrial T cells to high amounts of PGE2, a situation likely to occur during the extensive output of IFN-т by the conceptus. The quiescent state of the immune cells, reflected in down-regulated lymphocyte functions, may be related to the success of bovine gestation, since around Days 15-22 the conceptus expands and begins its first in-traepithelial infiltrations, being therefore directly exposed to maternal immune cells. Local reduction of IL-2 production would prevent the activation of NK cells into lym-phokine-activated killer cells that could be harmful to the conceptus.

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Prostaglandin E2 Regulates Both lnterleukin-2: DISCUSSION(3)

On the other hand, 0.1 ng/ml PGE2 stimulated GM-CSF gene expression, with no effect on IL-2 mRNA or DNA synthesis. Thus, the present study has shown a biphasic effect of PGE? acute exposure on GM-CSF gene expression: a stimulation at low concentrations and an inhibition at high concentrations. Biphasic effects of PGE2 have been reported to be mediated by PGE receptors of different affinities. Other studies have confirmed that GM-CSF responses to PGE2 are indeed complex and depend on the types of lymphocytes involved. It should be noted that the design of these experiments did not permit determination of whether the change in mRNA levels was due to transcription rate or to change in mRNA degradation.

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Prostaglandin E2 Regulates Both lnterleukin-2: DISCUSSION(2)


Embryonic attachment, early in the fourth week of gestation, is characterized by interdigitation of trophoblastic and maternal villi. The binucleate trophoblastic cells fuse with epithelial cells to form multinucleate giant cells, comprising around 50% of the maternal epithelial surface by Day 24. Trophoblastic cells are most certainly in contact with endometrial leukocytes, and the present observations suggest that the events accompanying early trophoblastic infiltration around Days 18-24 trigger immunorecognition and immunomo-dulation mechanisms. birth control pills

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Prostaglandin E2 Regulates Both lnterleukin-2: DISCUSSION(1)

During the bovine estrous cycle, uterine T lymphocytes increase in number from Day 11 onward. CD4+ cells, typically T-helper lymphocytes, are located in the endometrial stroma and outnumber CD8+ (suppressor/cytotoxic) cells, which constitute the prevalent lymphocytes in the uterine epithelium. Conversely, a decrease of intraepi-thelial lymphocytes is observed during bovine pregnancy, from around Day 21. This is preceded by the remarkable conceptus elongation occurring between Day 11 and Day 22 of pregnancy. This a critical time of bovine embryonic development, since it involves production of the conceptus secretory protein (peak at Days 15-19), now known as IFN-t, that maintains the corpus luteum. It also has strong immunosuppressive potential. The endometrial epithelial and stromal cells respond to this signal by substantially increasing their secretion of PGE2, a known immunomodulator. ventolin inhaler

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Prostaglandin E2 Regulates Both lnterleukin-2: RESULTS(4)

Preconditioning with PGE2 Modulates Lymphocyte Functions

As illustrated in Figure 5, A and B, PBL preconditioning with PGs for 72 h followed by a stimulation with ConA alone for 12 h had no significant effect (PGE2 p > 0.5; PGF2a p > 0.3) on IL-2 gene expression as compared to the PG0 control. GM-CSF mRNA levels were increased in a concentration-dependent manner when PGE2 was present in the pretreatment medium (Fig. 5, A and B). A maximum stimulation of 18 ± 2-fold (p < 0.0001) of the control value was obtained with 100 ng/ml PGE2. Again, PGF2„ had no significant effect (p > 0.7).

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