Requirement of autophagy for IL-1β secretion in human neutrophils.

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

Congreso; Reunión Anual de la SAI; 2014

Sociedad Argentina de Inmunología y Soc. Argentina de Investigación Clínica

Interleukin-1β(IL-1β) is a pro-inflammatory cytokine synthesized in the cytoplasm as a precursor, pro-IL-1β, which has to be proteolytically processed to acquire biological activity. In human neutrophils (PMN) IL-1βprocessing is dependent of caspase-1 and elastase and/or proteinase-3. The release of IL-1βdoes not follow the conventional ER-Golgi route of secretion, being secreted by poorly-defined non-conventional secretory pathways. The current study was undertaken to test the hypothesis that a non conventional autophagy (Au) mechanism is required for neutrophil IL-1β secretion. We have previously determined that the Au inhibitors 3-MA, wortmannin and Bafilomycin A1 inhibit IL-1βsecretion induced by LPS and LPS+ATP. In this study we determined that in response to these agonists, the secretion of IL-8, a cytokine whose release follows the canonical ER-Golgi pathway, was not regulated by the above mention inhibitors. We also observed that Au stimulation by starvation promoted IL-1βsecretion induced by both agonists (n=4; p