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Mediators of Inflammation
Volume 2016 (2016), Article ID 9605253, 10 pages
http://dx.doi.org/10.1155/2016/9605253
Research Article

PGC-1α-Dependent Mitochondrial Adaptation Is Necessary to Sustain IL-2-Induced Activities in Human NK Cells

1Department of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Sergio Livingstone 1007, Independencia, 8380492 Santiago, Chile
2Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Avenida Libertador Bernardo O’Higgins 3363, 9170022 Santiago, Chile

Received 3 November 2015; Revised 2 February 2016; Accepted 24 May 2016

Academic Editor: Jagadeesh Bayry

Copyright © 2016 Dante Miranda et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Human Natural Killer (NK) cells are a specialized heterogeneous subpopulation of lymphocytes involved in antitumor defense reactions. NK cell effector functions are critically dependent on cytokines and metabolic activity. Among various cytokines modulating NK cell function, interleukin-2 (IL-2) can induce a more potent cytotoxic activity defined as lymphokine activated killer activity (LAK). Our aim was to determine if IL-2 induces changes at the mitochondrial level in NK cells to support the bioenergetic demand for performing this enhanced cytotoxic activity more efficiently. Purified human NK cells were cultured with high IL-2 concentrations to develop LAK activity, which was assessed by the ability of NK cells to lyse NK-resistant Daudi cells. Here we show that, after 72 h of culture of purified human NK cells with enough IL-2 to induce LAK activity, both the mitochondrial mass and the mitochondrial membrane potential increased in a PGC-1α-dependent manner. In addition, oligomycin, an inhibitor of ATP synthase, inhibited IL-2-induced LAK activity at 48 and 72 h of culture. Moreover, the secretion of IFN-γ from NK cells with LAK activity was also partially dependent on PGC-1α expression. These results indicate that PGC-1α plays a crucial role in regulating mitochondrial function involved in the maintenance of LAK activity in human NK cells stimulated with IL-2.