INTRACELLULAR CHLORIDE MODULATES NLRP3 INFLAMMASOME AND IL-1B SECRETION

M. CLAUZURE; A. G. VALDIVIESO; M. MASSIP COPIZ; CONSUELO MORI; ASENSIO CRISTIAN JORGE ALEJANDRO; SANTA COLOMA T. A.

MAR DEL PLATA

Congreso; SAIC 2018; 2018

SAIC

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-1β, which starts an autocrine positive feedback loop. As the NLRP3 inflammasome is involved in IL-1β 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