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Abstract:

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.

Registro:

Documento: Artículo
Título:Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells
Autor:Zanetti, S.R.; Ziblat, A.; Torres, N.I.; Zwirner, N.W.; Bouzat, C.
Filiación:Instituto de Investigaciones Bioquímicas (INIBIBB), Universidad Nacional del Sur, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca, 8000, Argentina
Instituto de Biología y Medicina Experimental, CONICET, Ciudad de Buenos Aires, C1428ADN, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, C1428ADN, Argentina
Palabras clave: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
Año:2016
Volumen:291
Número:32
Página de inicio:16541
Página de fin:16552
DOI: http://dx.doi.org/10.1074/jbc.M115.710574
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
ISSN:00219258
CODEN:JBCHA
CAS:4 chloro n (3 quinuclidinyl)benzamide, 123464-89-1; alpha bungarotoxin, 11032-79-4; calcium ion, 14127-61-8; gamma interferon, 82115-62-6; interleukin 12, 138415-13-1; interleukin 18, 189304-55-0
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v291_n32_p16541_Zanetti

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Citas:

---------- APA ----------
Zanetti, S.R., Ziblat, A., Torres, N.I., Zwirner, N.W. & Bouzat, C. (2016) . Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells. Journal of Biological Chemistry, 291(32), 16541-16552.
http://dx.doi.org/10.1074/jbc.M115.710574
---------- CHICAGO ----------
Zanetti, S.R., Ziblat, A., Torres, N.I., Zwirner, N.W., Bouzat, C. "Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells" . Journal of Biological Chemistry 291, no. 32 (2016) : 16541-16552.
http://dx.doi.org/10.1074/jbc.M115.710574
---------- MLA ----------
Zanetti, S.R., Ziblat, A., Torres, N.I., Zwirner, N.W., Bouzat, C. "Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells" . Journal of Biological Chemistry, vol. 291, no. 32, 2016, pp. 16541-16552.
http://dx.doi.org/10.1074/jbc.M115.710574
---------- VANCOUVER ----------
Zanetti, S.R., Ziblat, A., Torres, N.I., Zwirner, N.W., Bouzat, C. Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells. J. Biol. Chem. 2016;291(32):16541-16552.
http://dx.doi.org/10.1074/jbc.M115.710574