Intracellular chloride modulates NLRP3 inflammasome and IL-1β secretion

CLAUZURE M; ANGEL GABRIEL VALDIVIESO; MASSIP-COPIZ, M.; MORI, CONSUELO;; ASENSIO, CRISTIAN; SANTA COLOMA TA,

Congreso; LXIII Reunión de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

(169) INTRACELLULAR CHLORIDE MODULATES NLRP3INFLAMMASOME AND IL-1B SECRETIONMariangeles Clauzure1, Angel Gabriel Valdivieso1, María MacarenaMassip Copiz1, Consuelo Mori1, Cristian J. A. Asensio1, Tomás Santa Coloma11Laboratory of Cell and Molecular Biology, Institute for BiomedicalResearch (BIOMED), Pontifical Catholic Universityof Buenos Aires (UCA) and National Scientific and TechnicalResearch Council (CONICET), Buenos Aires, Argentina.The impairment of the CFTR activity induces intracellular chloride(Cl-) accumulation. The anion Cl-, acting as a second messenger,in turn stimulates the secretion of IL-1B, which starts an autocrinepositive feedback loop. As the NLRP3 inflammasome is involved inIL-1B maturation and secretion, the aim of this study was to investigateif the NLRP3 inflammasome is modulated by Cl-. In that waywe studied the three proteins that form this complex: NLR familypyrin domain containing 3 (NRLP3), caspase-1 (CASP1), and apoptosis-associatedspeck-like protein containing a CARD (ASC/PYCARD).Here we show that NLRP3 and CASP1 are modulated bythe intracellular Cl- concentration, showing a biphasic response withmaximal expression and activity at 75 mM Cl- (p