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Mechanism of prostaglandin (PG)E2-induced prolactin expression in human T cells: Cooperation of two PGE2 receptor subtypes, E-prostanoid (EP) 3 and EP4, via calcium- and cyclic adenosine 5′-monophosphate-mediated signaling pathways

par Gerlo, Sarah;Verdood, Peggy;Peters, Elisabeth ;Kooijman, Ron;Gellersen, Birgit
Référence The Journal of immunology, 173, 10, page (5952-5962)
Publication Publié, 2004-11

Article révisé par les pairs

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Résumé :

We previously reported that prolactin gene expression in the T-leukemic cell line Jurkat is stimulated by PGE2 and that cAMP acts synergistically with Ca2+ or protein kinase C on the activation of the upstream prolactin promoter. Using the transcription inhibitor actinomycin D, we now show that PGE2-induced prolactin expression requires de novo prolactin mRNA synthesis and that PGE2 does not influence prolactin mRNA stability. Furthermore, PGE2-induced prolactin expression was inhibited by protein kinase inhibitor fragment 14-22 and BAPTA-AM, which respectively, inhibit protein kinase A- and Ca 2+-mediated signaling cascades. Using specific PGE2 receptor agonists and antagonists, we show that PGE2 induces prolactin expression through engagement of E-prostanoid (EP) 3 and EP4 receptors. We also found that PGE2 induces an increase in intracellular cAMP concentration as well as intracellular calcium concentration via EP4 and EP3 receptors, respectively. In transient transfections, 3000 bp flanking the leukocyte prolactin promoter conferred a weak induction of the luciferase reporter gene by PGE2 and cAMP, whereas cAMP in synergy with ionomycin strongly activated the promoter. Mutation of a C/EBP responsive element at -214 partially abolished the response of the leukocyte prolactin promoter to PGE2, cAMP, and ionomycin plus cAMP.