CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Autophagy modulates cytokine production in microglial cells.
Autor/es:
BUSSI, C; ARROYO, DS; PERALTA RAMOS, JM; GAVIGLIO, EA; IRIBARREN, P
Lugar:
Mar del Plata
Reunión:
Congreso; SAI / SAIC; 2014
Institución organizadora:
SAI/SAIC
Resumen:
Introduction: Autophagy is an essential, homeostatic processby which cells deliver their cytoplasmic material, including solublemacromolecules and organelles, to lysosomes for degradation. Recentdevelopments reveal a crucial role for the autophagy pathwayand proteins in immunity and inflammation. They balance the beneficialand detrimental effects of immunity and inflammation, andthereby may protect against infectious, autoimmune and inflammatorydiseases. Purpose: The aim of this study was to evaluatethe modulatory effect of autophagy on the cytokine productionin BV2 microglial cells. Experimental procedure: BV2 microglialcells were stimulated with TLRs ligands, such as PGN, Pam3 andLPS. Autophagy was induced before or after TLR stimulation byrapamycin or trehalose. Cytokines were determined in cell-freeculture supernatants by ELISA. Autophagy pathway was blockedusing 3-Methyladenine (3-MA), an inhibitor of type III Phosphatidylinositol3-kinases (PI-3K). Results: Our preliminary results show that stimulation of autophagic pathway downregulates theproduction of the cytokines IL1b, IL-6, IL-10 and TNFa (p<0.01).This effect was inhibited when cells were pre-treated with 3-MA(p<0.01). Interestingly, when 3-MA was added to cell cultures beforeTLR stimulation, an increase in the release of pro-inflammatorycytokines was observed compared with TLR stimulation alone(p<0.01). However, no changes were detected in IL-10 determination.Conclusions: The induction of autophagy negatively affectedthe cytokine release by microglial cells. In addition, the inhibitionof PI-3K showed a synergistic effect with TLR stimulation in therelease of pro-inflammatory cytokines. These results suggest thatthe class III PI-3K pathway plays an important role in modulatinginflammatory mediators. Additional studies are needed to betterunderstand the molecular mechanisms that mediate this process.