Interferon-tau stimulates granulocyte-macrophage colony-stimulating factorgene expression in bovine lymphocytes and endometrial stromal cells

Interferon-tau (IFN-tau), the antiluteotytic signal produced by the trophob last prior to implantation in ruminants, exhibits immunomodulatory properti es. It stimulates the production of prostaglandin (PG) E-2 in bovine endome trial cells via the induction of cyclooxygenase-2 (COX-2). We previously de monstrated that preconditioning lymphocytes with PGE(2) increases the expre ssion of granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytok ine that promotes conceptus growth and survival. Our goal in the present st udy was to evaluate the impact of IFN-tau on the expression of GM-CSF in bo vine peripheral blood lymphocytes (PBL) and endometrial epithelial and stro mal cells. Changes in PGE(2) production and mRNA level of COX-2 were also s tudied in PBL in response to IFN-tau. Gene expression was estimated by semi quantitative reverse transcription-polymerase chain reaction and Northern a nalysis. The expression of GM-CSF in PBL was stimulated by treatment with I FN-tau. Furthermore, CM-CSF mRNA levels were increased after preconditionin g PBL for 3 days with IFN-tau, followed by a 12-h restimulation without IFN -tau. Inhibition rather than stimulation of PCE2 production and COX-2 expre ssion in PBL during treatment with IFN-tau suggests a direct effect on GM-C SF expression. Moreover, GM-CSF expression was stimulated in uterine stroma l cells in response to IFN-tau. This study provides the first evidence for stimulation of GM-CSF expression by IFN-tau in both leukocytes and endometr ial stromal cells. In view of the role of GM-CSF on fetal growth and surviv al these results support the hypothesis that the conceptus mediates accommo dation mechanisms in the uterus during early pregnancy by modulating the ex pression of beneficial cytokines at the fetomaternal interface.