Cytokine-like effects of prolactin in human mononuclear and polymorphonuclear leukocytes.
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 beta-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.
Dogusan
Z
Z
Pharmacology Department (FARC), Medical School, Free University of Brussels (VUB), Building D Laarbeeklaan 103, B-1090 Brussels, Belgium.
Hooghe
R
R
Verdood
P
P
Hooghe-Peters
E L
EL
D000328:Adult; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001855:Bone Marrow Diseases / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D002364:Caseins / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D007107:Immune System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050856:Interferon Regulatory Factor-1; D053614:Janus Kinase 2; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008894:Milk Proteins; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011388:Prolactin / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011981:Receptors, Prolactin / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors; D014443:Tyrosine / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D002364:Caseins; D016207:Cytokines; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D050856:Interferon Regulatory Factor-1; D053614:Janus Kinase 2; D008894:Milk Proteins; D020928:Mitogen-Activated Protein Kinases; D019001:Nitric Oxide Synthase; D010750:Phosphoproteins; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014443:Tyrosine; D048051:p38 Mitogen-Activated Protein Kinases; C494257:IRF1 protein, human; C106644:SOCS3 protein, human; C494079:STAT1 protein, human; C507924:JAK2 protein, human