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Regular Article |
a Unité de Recherche en Ontogénie et Reproduction, Centre de Recherche du Centre Hospitalier de l'Université Laval, Ste-Foy, Québec, Canada G1V 4G2
b Centre de Recherche en Biologie de la Reproduction, Université Laval, Ste-Foy, Québec, Canada G1V 4G2
c Département d'Obstétrique et Gynécologie, Université Laval, Ste-Foy, Québec, Canada G1V 4G2
d Centre de Recherche en Reproduction Animale, Université de Montréal, St-Hyacinthe, Québec, Canada J2S 7C6
ABSTRACT
Interferon-tau (IFN-
), the antiluteolytic signal produced by the trophoblast prior to implantation in ruminants, exhibits immunomodulatory properties. It stimulates the production of prostaglandin (PG) E2 in bovine endometrial cells via the induction of cyclooxygenase-2 (COX-2). We previously demonstrated that preconditioning lymphocytes with PGE2 increases the expression of granulocyte–macrophage colony-stimulating factor (GM-CSF), a cytokine that promotes conceptus growth and survival. Our goal in the present study was to evaluate the impact of IFN- on the expression of GM-CSF in bovine peripheral blood lymphocytes (PBL) and endometrial epithelial and stromal cells. Changes in PGE2 production and mRNA levels of COX-2 were also studied in PBL in response to IFN-. Gene expression was estimated by semiquantitative reverse transcription–polymerase chain reaction and Northern analysis. The expression of GM-CSF in PBL was stimulated by treatment with IFN-. Furthermore, GM-CSF mRNA levels were increased after preconditioning PBL for 3 days with IFN-, followed by a 12-h restimulation without IFN-. Inhibition rather than stimulation of PGE2 production and COX-2 expression in PBL during treatment with IFN- suggests a direct effect on GM-CSF expression. Moreover, GM-CSF expression was stimulated in uterine stromal cells in response to IFN-. This study provides the first evidence for stimulation of GM-CSF expression by IFN- in both leukocytes and endometrial stromal cells. In view of the role of GM-CSF on fetal growth and survival, these results support the hypothesis that the conceptus mediates accommodation mechanisms in the uterus during early pregnancy by modulating the expression of beneficial cytokines at the fetomaternal interface.
1 This work was supported by grant 98-ER-2421 from the Fonds pour la Formation de Chercheurs et l'Aide à la Recherche (FCAR) and grants to M.A.F. and R.D.L. each from the Natural Sciences and Engineering Research Council of Canada (NSERC).
2 Correspondence: Raymond D. Lambert, Ontogénie et Reproduction T1-49, Centre de Recherche du Centre Hospitalier de l'Université Laval, 2705 Blvd. Laurier, Ste-Foy, PQ, Canada G1V 4G2. FAX: 418 654 2765; ray.lambert{at}crchul.ulaval.ca
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