Intracellular Chloride modulates NLRP3 inflammasome and IL-1B Secretion

ANGEL GABRIEL VALDIVIESO; CRISTIAN ASENSIO; MARIÁNGELES CLAUZURE; CONSUELO MORI; MARÍA MACARENA MASSIP COPIZ; TOMÁS A. SANTA COLOMA

MAR DEL PLATA

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2018

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 autocrine positive feedback loop. As the NLRP3 inflammasome is involved in IL-1B maturation and secretion, the aim of this study was to investigate if the NLRP3 inflammasome is modulated by Cl-. In that way we studied the three proteins that form this complex: NLR family pyrin domain containing 3 (NRLP3), caspase-1 (CASP1), and apoptosis-associated speck-like protein containing a CARD (ASC/PYCARD). Here we show that NLRP3 and CASP1 are modulated by the intracellular Cl-concentration, showing a biphasic response with maximal expression and activity at 75 mM Cl- (p