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

IA KEITELMAN, C MAIUMI SHIROMIZU, N ZGAJNAR, F SABBIONE, M MIGLIO RODRÍGUEZ, F FUENTES, M GUZMÁN, C JANCIC, J GALLETTI, P PEREYRA, M OSTROWSKI, M GALIGNIANA, A TREVANI

Congreso; LXIII Reunión Anual de SAIC; 2018

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