Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells

The homomeric α7 nicotinic receptor (nAChR) is one of the most abundant nAChRs in the central nervous system where it contributes to cognition, attention, and working memory. α7 nAChR is also present in lymphocytes, dendritic cells (DCs), and macrophages and it is emerging as an important drug targe...

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Autor principal: Ziblat, Andrea
Publicado: 2016
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Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v291_n32_p16541_Zanetti
http://hdl.handle.net/20.500.12110/paper_00219258_v291_n32_p16541_Zanetti
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spelling paper:paper_00219258_v291_n32_p16541_Zanetti2023-06-08T14:43:38Z Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells Ziblat, Andrea Calcium Cell death Cell membranes Cytology Cytotoxicity Enzyme activity Immune system Modulators Adaptive immune response Cell surface expression Central nervous systems Dendritic cells (DCs) Intracellular calcium concentration Intracellular stores Natural killer cells Positive allosteric modulator Cells 4 chloro n (3 quinuclidinyl)benzamide alpha bungarotoxin bungarotoxin receptor calcium ion gamma interferon immunoglobulin enhancer binding protein interleukin 12 interleukin 15 interleukin 18 messenger RNA natural killer cell receptor NKG2D allosterism alpha7 nAChR gene Article calcium cell level calcium mobilization cell maturation confocal microscopy controlled study cytokine production cytotoxicity dendritic cell down regulation flow cytometry gene expression regulation human human cell lymphocyte activation natural killer cell priority journal protein expression protein function reverse transcription polymerase chain reaction The homomeric α7 nicotinic receptor (nAChR) is one of the most abundant nAChRs in the central nervous system where it contributes to cognition, attention, and working memory. α7 nAChR is also present in lymphocytes, dendritic cells (DCs), and macrophages and it is emerging as an important drug target for intervention in inflammation and sepsis. Natural killer (NK) cells display cytotoxic activity against susceptible target cells and modulate innate and adaptive immune responses through their interaction with DCs. We here show that human NK cells also express α7 nAChR. α7 nAChR mRNA is detected by RT-PCR and cell surface expression of α7 nAChR is detected by confocal microscopy and flow cytometry using α-bungarotoxin, a specific antagonist. Both mRNA and protein levels increase during NK stimulation with cytokines (IL-12, IL-18, and IL-15). Exposure of cytokine-stimulated NK cells to PNU-282987, a specific α7 nAChR agonist, increases intracellular calcium concentration ([Ca2+]i) mainly released from intracellular stores, indicating that α7 nAChR is functional. Moreover, its activation by PNU-282987 plus a specific positive allosteric modulator greatly enhances the Ca2+ responses in NK cells. Stimulation of NK cells with cytokines and PNU-282987 decreases NF-κB levels and nuclear mobilization, down-regulates NKG2D receptors, and decreases NKG2D-dependent cell-mediated cytotoxicity and IFN-γ production. Also, such NK cells are less efficient to trigger DC maturation. Thus, our results demonstrate the anti-inflammatory role of α7 nAChR in NK cells and suggest that modulation of its activity in these cells may constitute a novel target for regulation of the immune response. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Fil:Ziblat, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v291_n32_p16541_Zanetti http://hdl.handle.net/20.500.12110/paper_00219258_v291_n32_p16541_Zanetti
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Calcium
Cell death
Cell membranes
Cytology
Cytotoxicity
Enzyme activity
Immune system
Modulators
Adaptive immune response
Cell surface expression
Central nervous systems
Dendritic cells (DCs)
Intracellular calcium concentration
Intracellular stores
Natural killer cells
Positive allosteric modulator
Cells
4 chloro n (3 quinuclidinyl)benzamide
alpha bungarotoxin
bungarotoxin receptor
calcium ion
gamma interferon
immunoglobulin enhancer binding protein
interleukin 12
interleukin 15
interleukin 18
messenger RNA
natural killer cell receptor NKG2D
allosterism
alpha7 nAChR gene
Article
calcium cell level
calcium mobilization
cell maturation
confocal microscopy
controlled study
cytokine production
cytotoxicity
dendritic cell
down regulation
flow cytometry
gene expression regulation
human
human cell
lymphocyte activation
natural killer cell
priority journal
protein expression
protein function
reverse transcription polymerase chain reaction
spellingShingle Calcium
Cell death
Cell membranes
Cytology
Cytotoxicity
Enzyme activity
Immune system
Modulators
Adaptive immune response
Cell surface expression
Central nervous systems
Dendritic cells (DCs)
Intracellular calcium concentration
Intracellular stores
Natural killer cells
Positive allosteric modulator
Cells
4 chloro n (3 quinuclidinyl)benzamide
alpha bungarotoxin
bungarotoxin receptor
calcium ion
gamma interferon
immunoglobulin enhancer binding protein
interleukin 12
interleukin 15
interleukin 18
messenger RNA
natural killer cell receptor NKG2D
allosterism
alpha7 nAChR gene
Article
calcium cell level
calcium mobilization
cell maturation
confocal microscopy
controlled study
cytokine production
cytotoxicity
dendritic cell
down regulation
flow cytometry
gene expression regulation
human
human cell
lymphocyte activation
natural killer cell
priority journal
protein expression
protein function
reverse transcription polymerase chain reaction
Ziblat, Andrea
Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells
topic_facet Calcium
Cell death
Cell membranes
Cytology
Cytotoxicity
Enzyme activity
Immune system
Modulators
Adaptive immune response
Cell surface expression
Central nervous systems
Dendritic cells (DCs)
Intracellular calcium concentration
Intracellular stores
Natural killer cells
Positive allosteric modulator
Cells
4 chloro n (3 quinuclidinyl)benzamide
alpha bungarotoxin
bungarotoxin receptor
calcium ion
gamma interferon
immunoglobulin enhancer binding protein
interleukin 12
interleukin 15
interleukin 18
messenger RNA
natural killer cell receptor NKG2D
allosterism
alpha7 nAChR gene
Article
calcium cell level
calcium mobilization
cell maturation
confocal microscopy
controlled study
cytokine production
cytotoxicity
dendritic cell
down regulation
flow cytometry
gene expression regulation
human
human cell
lymphocyte activation
natural killer cell
priority journal
protein expression
protein function
reverse transcription polymerase chain reaction
description The homomeric α7 nicotinic receptor (nAChR) is one of the most abundant nAChRs in the central nervous system where it contributes to cognition, attention, and working memory. α7 nAChR is also present in lymphocytes, dendritic cells (DCs), and macrophages and it is emerging as an important drug target for intervention in inflammation and sepsis. Natural killer (NK) cells display cytotoxic activity against susceptible target cells and modulate innate and adaptive immune responses through their interaction with DCs. We here show that human NK cells also express α7 nAChR. α7 nAChR mRNA is detected by RT-PCR and cell surface expression of α7 nAChR is detected by confocal microscopy and flow cytometry using α-bungarotoxin, a specific antagonist. Both mRNA and protein levels increase during NK stimulation with cytokines (IL-12, IL-18, and IL-15). Exposure of cytokine-stimulated NK cells to PNU-282987, a specific α7 nAChR agonist, increases intracellular calcium concentration ([Ca2+]i) mainly released from intracellular stores, indicating that α7 nAChR is functional. Moreover, its activation by PNU-282987 plus a specific positive allosteric modulator greatly enhances the Ca2+ responses in NK cells. Stimulation of NK cells with cytokines and PNU-282987 decreases NF-κB levels and nuclear mobilization, down-regulates NKG2D receptors, and decreases NKG2D-dependent cell-mediated cytotoxicity and IFN-γ production. Also, such NK cells are less efficient to trigger DC maturation. Thus, our results demonstrate the anti-inflammatory role of α7 nAChR in NK cells and suggest that modulation of its activity in these cells may constitute a novel target for regulation of the immune response. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
author Ziblat, Andrea
author_facet Ziblat, Andrea
author_sort Ziblat, Andrea
title Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells
title_short Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells
title_full Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells
title_fullStr Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells
title_full_unstemmed Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells
title_sort expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (nk) cells
publishDate 2016
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v291_n32_p16541_Zanetti
http://hdl.handle.net/20.500.12110/paper_00219258_v291_n32_p16541_Zanetti
work_keys_str_mv AT ziblatandrea expressionandfunctionalroleofa7nicotinicreceptorinhumancytokinestimulatednaturalkillernkcells
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