Abstract:

To explore the potential regulatory effects of trichostatin A (TSA) on survival and activity of natural killer (NK) cells. MethodsHuman peripheral blood lymphocytes（PBLs）or NK cells were separated or isolated from peripheral blood mononuclear cells (PBMCs) of healthy blood donors. Lymphokine activated killer (LAK) cells were generated by culturing PBLs in the presence of interleukin2 for 72?h. The cells were cultured in the presence or absence of TSA at the concentrations（0.01，0.1 and/or 1?μmol/L）for 12?h, 24?h and/or 48?h, respectively. Apoptotic cells in PBLs, LAK or purified NK cells were cytometrically quantified by dual labeling of propidium iodide (PI) and AnnexinV (AV). The proportion of apoptotic cells in PBLs were further defined by combined staining of AV, antiCD56 and antiCD3 antibodies, and flow cytometry method (FCM). NK cell cytolytic activity against leukemia cells (K562 leukemic cell line) was evaluated using a standard chromium51 release assay. ResultsTSA markedly induced apoptosis in PBLs and LAK cells in a dose and timedependent manner. The percentages of total apoptotic cells (AV+PI plus AV+PI+) in the TSA treatedPBLs or LAK cells were significantly higher than that in the untreated ones（P＜0.05）. Moreover, the percentage of total apoptotic cells in the purified resting NK cells treated by TSA(0.1?μmol/L) for 24?h was significantly higher than that in the control NK cells (P＜0.05). Importantly, the cytolytic activity of resting NK cells against leukemia cells significantly decreased after treatment with 0.1?μmol/L TSA for 12?h, as compared to the control NK cells（P＜0.01）. ConclusionsThe histone deacetylase inhibitor TSA can induce apoptosis in NK cells and LAK cells, and can affect NK cell cytotoxicity.

Key words: Histone deacetylase inhibitor; Natural killer cell; Apoptosis; Cytotoxicity