IMPACT OF SERINE PROTEASES IN HUMAN NEUTROPHIL INTERLEUKIN-1 BETA (IL-1Β) SECRETION

KEITELMAN, IRENE ANGÉLICA; SHIROMIZU, CAROLINA MAIUMI; ROSSO, DAVID ANTONIO; JANCIC, CAROLINA CRISTINA; FUENTES, FEDERICO; MARTI, MARCELO; GALLETTI, JEREMÍAS; SABBIONE FLORENCIA; ANALÍA TREVANI

Congreso; Reunion de Sociedades de Biociencias 2021; 2021

SAI-SAIC-AAFE-NANOMEDAR

Neutrophils (N) represent the first line of defense against bacterial and fungal infections. These granulocytes, which outnumber the rest of human immune cells found in circulation, are massively recruited to infectious foci where they contribute to the inflammatory responses by the release of cytokines. Among them is IL-1β, a leaderless protein which is synthesized in the cytosol as an inactive precursor, pro-IL-1β, that after processing is secreted by unconventional mechanisms.We previously determined that in response to LPS+ATP, human N release IL-1β by an autophagy-dependent mechanism and that both caspase-1- (C1) and N serine proteases (NSP)-activationare required for IL-1β secretion. Here we evaluated the role of both kinds of enzymes in pro-IL-1β processing in N isolated from healthy donors? peripheral blood. Our findings employing both ELISA and western blot indicated that inhibition of C1 with Ac-YVAD-CMK (50 μM) reduced IL-1β secretion but did not inhibit pro-IL-1β cleavage. By contrast, inhibition of NPS with AEBSF (0.35 mM) reduced IL-1β secretion and blocked pro-IL-1β processing (p