CHARACTERIZATION OF THE MECHANISM THAT TARGETS INTERLEUKIN-1 BETA (IL-1 Β) TOWARDS AUTOPHAGOSOMES FOR SECRETION

IRENE KEITELMAN, MAIUMI SHIROMIZU, NADIA ZGAJNAR, FLORENCIA SABBIONE, MAXIMILIANO MIGLIO, MAURICIO GUZMÁN, CAROLINA JANCIC, JEREMÍAS GALLETTI, PEHUÉN PEREYRA GERBER, MATÍAS OSTROWSKI, MARIO GALIGNIANA, ANALÍA TREVANI

Congreso; LXIII Reunión Anual de SAIC; 2018

SAIC

IL-1 is a major proinflammatory cytokine synthesized in the cytoplasm as an inactive precursor that is activated by proteolytic cleavage. It is a leaderless cytosolic protein that is secreted by unconventional mechanisms different from the classical ER-Golgi pathway. Our previous studies indicated that neutrophil cytoplasmic IL-1β is targeted to an autophagic compartment and is secreted by an unconventional secretory autophagic mechanism. The aim of this study was to gain insights into the mechanisms involved in IL-1β loading into the vesicles from which IL-1 is going to be secreted by human neutrophils. Neutrophils were isolated from healthy donors and stimulated for 5 h with LPS+ATP. We first investigated by ELISA if IL-1β is released inside extracellular vesicles. We found that 783±223 pg/ml of IL-1β were released to supernatants devoid of extracellular vesicles and 47±14 pg/ml were released inside extracellular vesicles (n=4; p