Up-modulation of interferon-gamma mediates the enhancement of spontanous cytotoxicity in prolactin-activated natural killer cells.
Prolactin (PRL) has been shown to participate in lymphocyte activation. In particular, the constitutive natural killer (NK) and the lymphokine-activated killer (LAK) cytotoxicity of CD56+ CD16+ cells is increased by its physiological to supraphysiological concentrations. As PRL has been shown to up-regulate the production of interferon-gamma (IFN-gamma) by peripheral blood mononuclear cells, we studied its effect on IFN-gamma production by NK cells as a possible mechanism of autocrine activation of cytotoxicity. Released and intracellular IFN-gamma, as well as IFN-gamma mRNA expression, were increased by pituitary and recombinant human PRL, which stimulated optimal NK and LAK cytotoxicity. Treatment with blocking anti-IFN-gamma monoclonal antibody (mAb) selectively affected PRL-increased killing of K562 targets, demonstrating that PRL-mediated enhancement of spontaneous cytotoxicity depends, at least in part, on up-regulation of IFN-gamma.
Matera
L
L
Department of Internal Medicine, University of Turin, Italy.
Contarini
M
M
Bellone
G
G
Forno
B
B
Biglino
A
A
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019898:Autocrine Communication; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D011388:Prolactin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D011388:Prolactin