Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10872609 | FEBS Letters | 2007 | 6 Pages |
Abstract
Treatment of transformed cells from leukemia or solid tumors with histone deacetylase inhibitors (HDACi) was shown to increase their sensitivity to NK cell lysis. In this study, treatment of IL-2-activated NK cells with HDACi including suberoylanilide hydroxamic acid and valproic acid was studied. Both drugs at therapeutic concentrations inhibited NK cell cytotoxicity on human leukemic cells. This inhibition was associated with decreased expression and function of NK cell activating receptors NKp46 and NKp30 as well as impaired granule exocytosis. NFκB activation in IL-2-activated NK cells was inhibited by both HDACi. Pharmacologic inhibition of NFκB activity resulted in similar effects on NK cell activity like those observed for HDACi. These results demonstrate for the first time that HDACi prevent NK cytotoxicity by downregulation of NK cell activating receptors probably through the inhibition of NFκB activation.
Keywords
KirVPANKG2DNKG2AIMDMSAHALFA-1NCRMICA/BHDACiIL-2FCSDNAM-1RFUmAbnatural killerNFκBMonoclonal antibodySuberoylanilide hydroxamic acidIscove’s Modified Dulbecco’s MediumInterleukin-2fetal calf serumNK cellsCytotoxicitylymphocyte function antigen-1nuclear factor kappa Bphycoerythrinhistone deacetylase inhibitorsrelative fluorescent unitsValproic acidkiller immunoglobulin-like receptors
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Authors
Henry Ogbomo, Martin Michaelis, Jörg Kreuter, Hans Wilhelm Doerr, Jindrich Jr.,