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Signal transduction and modulation of gene expression by prolactin in human leukocytes

par Hooghe, Robert;Devos, Stéphane;Dogusan, Zeynep ;Peters, Elisabeth
Référence Neuroimmune biology, 2, C, page (123-136)
Publication Publié, 2002

Article révisé par les pairs

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Résumé :

Leukocytes have receptors for prolactin (PRL) and the immune system is indeed a direct target of this pleiotropic hormone that originates from the pituitary gland but also, to a minor extent, from other sites such as the lymphoid system. PRL thus could act on leukocytes in an endocrine, a paracrine or an autocrine fashion. Seminal studies were performed in the PRL-responsive Nb2 rat T-cell lymphoma line. PRL signals mainly through Janus kinase (Jak)/signal transducers and activators of transcription (Stat) and by the mitogen-activated protein-kinase (MAP-K) pathways. PRL induces the expression of genes that are involved in innate and acquired immune responses. Our own studies were done with normal rat and human leukocytes. The expression of receptors for PRL was detected with PCR in rat splenocytes and bone marrow cells and in human peripheral blood mononuclear cells (PBMC). In human granulocytes, however, receptor expression was below detection level. Exposure to physiological concentrations of PRL led to the activation of the Jak-2 and Stat-5 in rat cells and in human PBMC. In human granulocytes, PRL activated Stat-1 but not Jak-2 nor Stat-5. PRL stimulated the expression of the interferon regulatory factor (IRF)-1 gene in rat spleen and bone marrow cells. In man, genes induced by PRL include several members of the SOCS-family (suppressors of cytokine signaling), inductible nitric oxide synthase (iNOS) and IRF-1, which are all highly relevant to immune responses. Further work should identify the functional consequences of these biochemical events at the level of survival, proliferation, differentiation and functional activity. For instance, the sharing of signaling pathways accounts for synergy between PRL and cytokines such as IL-2 and IL-12. Also, PRL induces SOCS factors thereby modulating signal transduction by cytokines. © 2002 Elsevier B.V. All rights reserved.