Synergistic effect of prolactin on IFN-gamma-mediated growth arrest in human monoblastic cells: correlation with the up-regulation of IFN-gamma receptor gene expression.
Interferon-gamma (IFN-gamma) stimulates the development of monocytic features in human myeloid precursors. Because transcriptional regulation of IFN-gamma and the pituitary hormone prolactin (PRL) has been described to involve common Jak-STAT pathways, we addressed here the question of whether PRL plays a role in monoblastic (U937) cell growth and macrophage maturation. In contrast to IFN-gamma, PRL did not affect U937 cell growth nor induction of differentiation as assessed by the unchanged cell surface expression of maturation markers CD11b and HLA-DR class II. However, PRL in synergy with IFN-gamma inhibited, in a time- and dose-dependence, proliferation of U937 cells without influencing their maturation induced by IFN-gamma. IFN-gamma and PRL both affected the expression of the IFN-gamma receptor (IFN-gamma R) gene by increasing IFN-gamma R mRNA levels. The rise in IFN-gamma R transcripts was accompanied by a low but significant release of IL-6 which has previously been shown to stabilize IFN-gamma R mRNA. Moreover, a transient increase in surface expression of IFN-gamma R was observed in U937 cells treated by IFN-gamma alone or in combination with PRL, whereas no apparent modulation of cell surface IFN-gamma R was observed in cells treated with PRL. Lastly, PRL did not induce transcriptional activation in IFN-gamma inducible IRF-1 and Fc gamma RI genes in U937 cells. Together, our data indicate that IL-6 secretion and increased expression of the IFN-gamma R gene correlate with U937 cell growth arrest induced by IFN-gamma and PRL, probably through a signaling mechanism which does not involve the Stat 1/IRF-1 pathway.
Sedo
A
A
Unité 365 INSERM Institut Curie, Paris, France.
Van Weyenbergh
J
J
Rouillard
D
D
Bauvois
B
B
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics; D011388:Prolactin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D007375:Interleukin-1; D015850:Interleukin-6; D016177:Macrophage-1 Antigen; D010750:Phosphoproteins; D012333:RNA, Messenger; D017452:Receptors, IgG; D017471:Receptors, Interferon; D007371:Interferon-gamma; D011388:Prolactin