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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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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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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1768543453259497472 |