Evidence that autophagy is involved in Interleukin-1β exportation in human neutrophils

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

Conferencia; Buenos Aires Conferences 2013 Autophagy: Molecular Mechanisms in Biology and Diseases.; 2013

Neutrophils are essential players in acute inflammatory responses. Upon stimulation, neutrophils activate NADPH oxidase, generating an array of reactive oxygen species (ROS). Interleukin-1β (IL-1β) is a major pro-inflammatory cytokine synthesized in the cytoplasm as a precursor, pro-IL-1β. To become biologically active, pro-IL-1β has to be proteolytically processed. We previously demonstrated that in human neutrophils stimulated with LPS and LPS plus ATP, caspase-1 and elastase and/or proteinase-3 are involved in the processing of pro-IL-1β. We also found that ROS are required for IL-1β exportation. The release of IL-1 does not follow the conventional ER-Golgi route of secretion, being secreted by poorly-defined non-conventional secretory pathways. Considering that LPS stimulates the production of ROS, which were shown to trigger autophagy in neutrophils, we hypothesized that autophagy is involved in IL-1β secretion in these cells. We found that upon LPS+ATP stimulation, the autophagy inhibitors 3-methyladenine and wortmannin markedly reduced IL-1β secretion (p