Evidence that autophagy controls interleukin-1β destination in human neutrophils.

IULA L; GABELLONI ML; SABBIONE F; KEITELMAN I; JANCIC C; TREVANI AS

Los Cocos, Córdoba

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 2013

Sociedad Argentina de Inmunología

Interleukin-1β (IL-1β) is a major pro-inflammatory cytokine synthesized in the cytoplasm as a precursor, pro-IL-1β, which has to be proteolytically processed to become biologically active. Previously we demonstrated that in response to LPS and LPS plus ATP, human neutrophils process pro-IL-1β by means of caspase-1 and elastase and/or proteinase-3. We also found that NADPH-oxidase derived reactive oxygen species (ROS) are required for IL-1β exportation. The mechanisms involved in IL-1b secretion are still unclear. On the basis that LPS stimulates the production of ROS, which were shown to trigger autophagy in neutrophils, in this study we tested the hypothesis that autophagy is involved in IL-1β secretion in these cells. Our findings indicated that upon LPS+ATP stimulation, the autophagy inhibitor 3-methyladenine concentration-dependently inhibited IL-1β secretion (141,9 mean ± 37,3 SEM pg/ml IL-1β; 27,95±20,24; 6,84±4,77; 2,04±1,53 for 0; 2.5; 5; and 10 mM 3-MA respectively, p