Cytokine-like effects of prolactin in human mononuclear and polymorphonuclear leukocytes

• Published in: Journal of neuroimmunology 2001, Vol.120 (1), p.58-66
• Main Authors: Dogusan, Z, Hooghe, R, Verdood, P, Hooghe-Peters, E.L
• Format: Article
• Language: English
• Subjects: Adult; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; Autoimmune Diseases - physiopathology; Bone Marrow Diseases - drug therapy; Bone Marrow Diseases - immunology; Bone Marrow Diseases - physiopathology; Caseins - metabolism; Cells, Cultured - drug effects; Cells, Cultured - immunology; Cytokines - immunology; Cytokines - metabolism; Cytokines - pharmacology; DNA-Binding Proteins - drug effects; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Granulocytes - drug effects; Granulocytes - immunology; Granulocytes - metabolism; Humans; Immediate-Early Proteins - genetics; Immune System - drug effects; Immune System - immunology; Immune System - metabolism; iNOS; Interferon Regulatory Factor-1; IRF-1; JAK/Stat; Jak2 kinase; Janus Kinase 2; Leukocytes; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Male; Milk Proteins; Mitogen-Activated Protein Kinases - drug effects; Mitogen-Activated Protein Kinases - metabolism; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - metabolism; Nitric Oxide Synthase - genetics; p38 MAPK; p38 Mitogen-Activated Protein Kinases; Phosphoproteins - genetics; Phosphorylation - drug effects; PRL; prolactin; Prolactin - immunology; Prolactin - metabolism; Prolactin - pharmacology; Protein-Tyrosine Kinases - drug effects; Protein-Tyrosine Kinases - immunology; Protein-Tyrosine Kinases - metabolism; Proteins - genetics; Proto-Oncogene Proteins; Receptors, Prolactin - drug effects; Receptors, Prolactin - immunology; Receptors, Prolactin - metabolism; Repressor Proteins; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Signal Transduction - drug effects; Signal Transduction - immunology; SOCS; STAT1 Transcription Factor; STAT5 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Trans-Activators - drug effects; Trans-Activators - metabolism; Transcription Factors; Tyrosine - drug effects; Tyrosine - immunology; Tyrosine - metabolism
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(01)00420-9

Some biochemical events following the binding of prolactin (PRL) to its receptor in normal human leukocytes were investigated. PRL enhanced JAK2 phosphorylation in peripheral blood mononuclear cells (PBMC) but not in granulocytes. PRL also induced phosphorylation of Stat-5 in PBMC and Stat-1 in granulocytes. Subsequent binding of Stat-5- and of Stat-1-like molecules to a GAS responsive element from the β-casein promoter was detected by EMSA. p38 MAPK (but not p42/p44 MAPK) was activated by PRL in both leukocyte populations. PRL induced iNOS and CIS mRNA expression in granulocytes. Increased expression of IRF-1 and SOCS-2 was observed in granulocytes and of SOCS-3 and iNOS in PBMC. Similar effects were obtained with ovine and human PRL. Antiserum to PRL reduced iNOS and IRF-1 expression induced by PRL in granulocytes and reduced iNOS expression in PBMC. Also, pretreatment of granulocytes with a p38 MAPK inhibitor (SB 203580) prevented in part PRL-induced iNOS and IRF-1 expression. In PBMC, the p38 inhibitor decreased PRL-induced iNOS gene expression. These results indicate that PRL-induced gene regulation in leukocytes requires the activation of at least two different pathways: the Stat and the MAP kinase pathways. Moreover, although PRL activates Stat in both leukocyte types, signal transduction is different in granulocytes and in PBMC. Most importantly, PRL modulates the expression of genes crucial to leukocyte function. The present findings reinforce the concept that PRL has “cytokine-like” activity in human leukocytes.