IRIBARREN PABLO
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 process
by which cells deliver their cytoplasmic material, including soluble
macromolecules and organelles, to lysosomes for degradation. Recent
developments reveal a crucial role for the autophagy pathway
and proteins in immunity and inflammation. They balance the beneficial
and detrimental effects of immunity and inflammation, and
thereby may protect against infectious, autoimmune and inflammatory
diseases. Purpose: The aim of this study was to evaluate
the modulatory effect of autophagy on the cytokine production
in BV2 microglial cells. Experimental procedure: BV2 microglial
cells were stimulated with TLRs ligands, such as PGN, Pam3 and
LPS. Autophagy was induced before or after TLR stimulation by
rapamycin or trehalose. Cytokines were determined in cell-free
culture supernatants by ELISA. Autophagy pathway was blocked
using 3-Methyladenine (3-MA), an inhibitor of type III Phosphatidylinositol
3-kinases (PI-3K). Results: Our preliminary results show that stimulation of autophagic pathway downregulates the
production 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 before
TLR stimulation, an increase in the release of pro-inflammatory
cytokines 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 affected
the cytokine release by microglial cells. In addition, the inhibition
of PI-3K showed a synergistic effect with TLR stimulation in the
release of pro-inflammatory cytokines. These results suggest that
the class III PI-3K pathway plays an important role in modulating
inflammatory mediators. Additional studies are needed to better
understand the molecular mechanisms that mediate this process.