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

KEITELMAN I; SHIROMIZU, CAROLINA MAIUMI; ZGAJNA, N; SABBIONE F; MIGLIO RODRIGUEZ M; FUENTES F; GUZMAN M; JANCIC C; GALLETTI J; GERBER, PEHUÉN PEREYRA; OSTROWSKI M; GALIGNINANA M; TREVANI AS

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología. Mar del Plata 14-17 de noviembre, 2018, Argentina.; 2018

Sociedad Argentina de Inmunología

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-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 donors and 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 extracellular vesicles (n=4; p