INVESTIGADORES
ZWIRNER Norberto Walter
congresos y reuniones científicas
Título:
Anti-inflammatory effects of alpha7 nicotinic receptor on human NK cells
Autor/es:
ZANETTI, SAMANTA ROMINA; ZIBLAT, ANDREA; ZWIRNER, NORBERTO WALTER; BOUZAT, CECILIA BEATRIZ
Lugar:
Buenos Aires
Reunión:
Congreso; IV Latinamerican Society for Immunodeficiencies (LASID) Meeting, LXIII Meeting of the Argentinean Society of Immunology and II French-Argentinean Immunology Meeting.; 2015
Institución organizadora:
Latinamerican Society for Immunodeficiencies (LASID) y Sociedad Argentina de Inmunología (SAI)
Resumen:
Nicotinic acetylcholine receptors (nAChRs) areligand-gated ion channels that mediate calcium (Ca2+) influx anddiverse intracellular signals in neuronal and non-neuronal cells. Previously,we determined by PCR and qPCR that the expression of a7 mRNA increases 3-foldafter activation of NK cells with IL-12, IL-18 and IL-15. Also, cell surfaceexpression of α7 is detectedusing Alexa488-labeled a-bungarotoxin (a-BGT, a specific antagonist of a7) in cytokine-stimulated but not in resting NK cells.In the present study, we investigated the functionality of α7 nAChR in NK cells as well as the regulation by agonists and antagonists of a7 of their effectorfunctions elicited by cytokines. By confocal microscopy, we determined thatin cytokine-stimulated NK cells the presence of PNU-282987 (a specific agonist of a7) and nicotine plus PNU-120596 (a specific positive allostericmodulator of a7) induces rapid increase of intracellular Ca2+,indicating that a7 is functional in these cells. This effect is notobserved in the absence of the a7 ligands or in cells preincubated with a-BGT. We also observed that in cytokine-stimulated NKcells the presence of PNU-282987: i) down-regulates the expression of NKG2D, ii)reduces the production of IFN-g, and iii) does not affect the NK cell-mediatedcytotoxicity against K562 target cells. Overall, our results indicate that IFN-γproduction and phenotype of NK cells can be negatively regulated by activation ofa7 nAChR. These effects may contribute to tumor progressionor dissemination of intracellular infections where NKG2D and IFN-g play a critical role.