Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Miranda, Dante, Jara, Claudia, Ibañez, Jorge, Ahumada, Viviana, Acuña-Castillo, Claudio, Martin, Adrian, Córdova, Alexandra, Montoya, Margarita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931085/
https://www.ncbi.nlm.nih.gov/pubmed/27413259
http://dx.doi.org/10.1155/2016/9605253
_version_ 1782440835552378880
author Miranda, Dante
Jara, Claudia
Ibañez, Jorge
Ahumada, Viviana
Acuña-Castillo, Claudio
Martin, Adrian
Córdova, Alexandra
Montoya, Margarita
author_facet Miranda, Dante
Jara, Claudia
Ibañez, Jorge
Ahumada, Viviana
Acuña-Castillo, Claudio
Martin, Adrian
Córdova, Alexandra
Montoya, Margarita
author_sort Miranda, Dante
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4931085
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-49310852016-07-13 PGC-1α-Dependent Mitochondrial Adaptation Is Necessary to Sustain IL-2-Induced Activities in Human NK Cells Miranda, Dante Jara, Claudia Ibañez, Jorge Ahumada, Viviana Acuña-Castillo, Claudio Martin, Adrian Córdova, Alexandra Montoya, Margarita Mediators Inflamm Research Article 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. Hindawi Publishing Corporation 2016 2016-06-20 /pmc/articles/PMC4931085/ /pubmed/27413259 http://dx.doi.org/10.1155/2016/9605253 Text en Copyright © 2016 Dante Miranda et al. https://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Research Article
Miranda, Dante
Jara, Claudia
Ibañez, Jorge
Ahumada, Viviana
Acuña-Castillo, Claudio
Martin, Adrian
Córdova, Alexandra
Montoya, Margarita
PGC-1α-Dependent Mitochondrial Adaptation Is Necessary to Sustain IL-2-Induced Activities in Human NK Cells
title PGC-1α-Dependent Mitochondrial Adaptation Is Necessary to Sustain IL-2-Induced Activities in Human NK Cells
title_full PGC-1α-Dependent Mitochondrial Adaptation Is Necessary to Sustain IL-2-Induced Activities in Human NK Cells
title_fullStr PGC-1α-Dependent Mitochondrial Adaptation Is Necessary to Sustain IL-2-Induced Activities in Human NK Cells
title_full_unstemmed PGC-1α-Dependent Mitochondrial Adaptation Is Necessary to Sustain IL-2-Induced Activities in Human NK Cells
title_short PGC-1α-Dependent Mitochondrial Adaptation Is Necessary to Sustain IL-2-Induced Activities in Human NK Cells
title_sort pgc-1α-dependent mitochondrial adaptation is necessary to sustain il-2-induced activities in human nk cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931085/
https://www.ncbi.nlm.nih.gov/pubmed/27413259
http://dx.doi.org/10.1155/2016/9605253
work_keys_str_mv AT mirandadante pgc1adependentmitochondrialadaptationisnecessarytosustainil2inducedactivitiesinhumannkcells
AT jaraclaudia pgc1adependentmitochondrialadaptationisnecessarytosustainil2inducedactivitiesinhumannkcells
AT ibanezjorge pgc1adependentmitochondrialadaptationisnecessarytosustainil2inducedactivitiesinhumannkcells
AT ahumadaviviana pgc1adependentmitochondrialadaptationisnecessarytosustainil2inducedactivitiesinhumannkcells
AT acunacastilloclaudio pgc1adependentmitochondrialadaptationisnecessarytosustainil2inducedactivitiesinhumannkcells
AT martinadrian pgc1adependentmitochondrialadaptationisnecessarytosustainil2inducedactivitiesinhumannkcells
AT cordovaalexandra pgc1adependentmitochondrialadaptationisnecessarytosustainil2inducedactivitiesinhumannkcells
AT montoyamargarita pgc1adependentmitochondrialadaptationisnecessarytosustainil2inducedactivitiesinhumannkcells