Characterization of the mechanism that targets interleukin-1beta (IL-1beta) towards autophagosomes for secretion

KEITELMAN, IRENE A; SABBIONE, FLORENCIA; GUZMÁN, MAURICIO; PEREYRA GERBER, PEHUEN; ANALÍA, TREVANI S.; ZGAJNAR, NADIA ROMINA; FUENTES, FEDERICO; GALLETTI, JEREMÍAS; GALIGNIANA, MARIO; SHIROMIZU, CAROLINA MAIUMI; MIGLIO RODRIGUEZ, MAXIMILIANO; JANCIC, CAROLINA C.; OSTROWSKI, MATIAS

Mar del Plata

Congreso; 66 Reunión Anual de la Sociedad Argentina de Inmunología; 2018

SAI - SAIC

IL-1β 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-1β 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