PROSTAGLANDIN E-2 REGULATES BOTH INTERLEUKIN-2 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GENE-EXPRESSION IN BOVINE LYMPHOCYTES

Prostaglandin E-2 (PGE(2)) is known to inhibit interleukin-2 (IL-2) pr oduction by human peripheral blood lymphocytes (PBL) and to increase g ranulocyte-macrophage colony-stimulating factor (GM-CSF). In many spec ies with hemochorial placentation, down-regulation of IL-2 appears nec essary to impede early embryonic demise, whereas up-regulation of GM-C SF increases embryonic growth and survival. It is not known whether th e same mechanisms are involved in a species with a less invasive place nta. PGE(2) is synthesized during early bovine gestation by the endome trium and by the embryo, and it may therefore be involved in regulatin g IL-2 and GM-CSF in this species. Our goal was to evaluate the impact of PGE(2) on cellular proliferation and on IL-2 and GM-CSF gene expre ssion in bovine PRL. Incorporation of [H-3]thymidine was used to study DNA synthesis. Gene expression was estimated by semiquantitative poly merase chain reaction using bovine-specific primers and by Northern an alysis using amplified bovine cDNAs as probes. The DNA synthesis and I L-2 mRNA levels of bovine PBL stimulated by concanavalin A (ConA) were greatly reduced by PGE(2) in direct-treatment studies. Under the same conditions, GM-CSF gene expression was also inhibited. However, pretr eatment of PBL for 72 h with ConA and PGE(2), followed, after washing, by an incubation with ConA alone for 12 h resulted in reduced DNA syn thesis, stable expression of IL-2, and a dramatic increase of GM-CSF m RNA levels. This is the first evidence in the bovine model that direct treatment with PGE(2) down-regulates IL-2 and GM-CSF mRNA levels and that preconditioning with PGE(2) stimulates GM-CSF gene expression. We propose that PGE(2), either from embryonic or from endometrial compar tments, induces bovine PBL to undergo functional changes, affecting ce llular proliferation and cytokine production in order to accommodate t he developing conceptus.