Please use this identifier to cite or link to this item: https://repositorio.uca.edu.ar/handle/123456789/14599
Título : NLR family pyrin domain containing 3 (NLRP3) and caspase 1 (CASP1) modulation by intracellular Cl– concentration
Autor : Clauzure, Mariángeles 
Valdivieso, Ángel Gabriel 
Dugour, Andrea V. 
Mori, Consuelo 
Massip Copiz, María Macarena 
Aguilar, María Á. 
Sotomayor, Verónica 
Asensio, Cristian J. A. 
Figueroa, Juan M. 
Santa Coloma, Tomás Antonio 
Palabras clave : FIBROSIS QUISTICA REGULADOR DE LA CONDUCTANCIA TRANSMEMBRANAREGULADOR DE CONDUCTANCIA TRANSMEMBRANA DE LA FIBROSIS QUÍSTICASEÑALIZACION AUTOCRINAANIÓN CLORUROCANAL DE CLORUROINFLAMASOMAINTERLEUCINANLRP3SEGUNDO MENSAJEROSGK1
Fecha de publicación : 2021
Editorial : Wiley-Blackwell
Cita : Clauzure, M. et al. NLR family pyrin domain containing 3 (NLRP3) and caspase 1 (CASP1) modulation by intracellular Cl– concentration [en línea]. Immunology. 2021,163(4). doi: 10.1111/imm.13336. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/14599
Resumen : Abstract: The impairment of the cystic fibrosis transmembrane conductance regulator (CFTR) activity induces intracellular chloride (Cl– ) accumulation. The anion Cl– , acting as a second messenger, stimulates the secretion of interleukin-1β (IL-1β), which starts an autocrine positive feedback loop. Here, we show that NLR family pyrin domain containing 3 (NLRP3) and caspase 1 (CASP1) are indirectly modulated by the intracellular Cl– concentration, showing maximal expression and activity at 75 mM Cl– , in the presence of the ionophores nigericin and tributyltin. The expression of PYD and CARD domain containing (PYCARD/ASC) remained constant from 0 to 125 mM Cl– . The CASP1 inhibitor VX-765 and the NLRP3 inflammasome inhibitor MCC950 completely blocked the Cl– - stimulated IL-1β mRNA expression and partially the IL-1β secretion. DCF fluorescence (cellular reactive oxygen species, cROS) and MitoSOX fluorescence (mitochondrial ROS, mtROS) also showed maximal ROS levels at 75 mM Cl– , a response strongly inhibited by the ROS scavenger N-acetyl-L-cysteine (NAC) or the NADPH oxidase (NOX) inhibitor GKT137831. These inhibitors also affected CASP1 and NLRP3 mRNA and protein expression. More importantly, the serum/glucocorticoid regulated kinase 1 (SGK1) inhibitor GSK650394, or its shRNAs, completely abrogated the IL-1β mRNA response to Cl– and the IL-1β secretion, interrupting the autocrine IL-1β loop. The results suggest that Cl– effects are mediated by SGK1, in which under Cl– modulation stimulates the secretion of mature IL-1β, in turn, responsible for the upregulation of ROS, CASP1, NLRP3 and IL-1β itself, through autocrine signalling.
URI : https://repositorio.uca.edu.ar/handle/123456789/14599
ISSN : 1365-2567 (online)
0019-2805
Disciplina: MEDICINA
DOI: 10.1111/imm.13336
Derechos: Acceso abierto
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