PMA inhibits NK cell generation, cytotoxic activity and NK-1.1 expression.
We investigated the role of protein kinase C activator phorbol 12-myristate 13-acetate (PMA) on IL-2-driven NK cell differentiation, by using an in vitro model previously set up by our laboratory. Bone marrow precursor cells, from mice treated with 5-fluorouracil (FUBM), when cultured with IL-2, generated mature NK cells. The biochemical system involved in this process has not yet been defined. We investigated the possible mechanism by analyzing the effect of PCK activator PMA on NK cell differentiation and lytic activity of mature NK cells. We now report that: (1) PMA inhibited the IL-2-induced NK cell differentiation and induced development of cells which lyse the NK-resistant target P815. (2) PMA inhibited the lytic ability of mature NK cells against NK-sensitive target YAC-1. We evaluated the effects of PMA using the expression of NK-associated antigen NK-1.1 and the ability to lyse YAC target as parameters of NK cell differentiation. PMA down-regulated both these parameters, reducing their expression during the differentiation process of NK cells and inducing down-modulation of these in mature NK cells. The results suggest that PKC regulatory control could be under the process of differentiation and activation of NK cells.
Ayroldi
E
E
Institute of Pharmacology, University of Perugia, Italy.
Cannarile
L
L
Migliorati
G
G
Riccardi
C
C
D000818:Animals; D000941:Antigens / Q000187:drug effects*; D000950:Antigens, Ly; D000954:Antigens, Surface; D002454:Cell Differentiation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D007376:Interleukin-2; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D013755:Tetradecanoylphorbol Acetate