IRIBARREN PABLO
Congresos y reuniones científicas
Título:
Peptidoglycan from staphylococcus aureus induces death of microglial cells by a caspase-3 independent pathway
Autor/es:
ARROYO, DS; SORIA, JA; GAVIGLIO, EA; GARCIA-KELLER, C; CANCELA, LM; RODRIGUEZ-GALAN, MC; WANG, JM; IRIBARREN, P
Reunión:
Congreso; Innate Immunity: Sensing the Microbes and Damage Signals; 2012
Institución organizadora:
Keystone Symposia
Resumen:
Microglial cells (MC) are involved in central nervous system diseases. Our preliminary studies have shown that stimulation of MC with peptidoglycan from Staphylococcus aureus (PGN, TLR2
agonist) induced the production of several neurotoxic factors and cell death.
Our goal was to study the mechanisms responsible for the PGN-induced cell death. PGN promoted an increase in the frequency of annexin V/7-AAD double positive MC (late apoptotic/necrotic
cells), after 48 h of treatment (81% vs 7%, p<0,0001), without the presence of annexin V single positive cells (early apoptotic cells) at any time point.
In addition, BV2 cells stimulated with PGN showed, by electronic microscopy, the presence of double membrane vesicles (compatible with the ultrastructure of autophagic vesicles) and strong
vacuolization in the cell cytoplasm. These findings correlated with both a particulated pattern of cytoplasmic staining with monodansylcadaverine (MDC), and detection of increased cleaved LC3B
(LC3B II) by western blot. These effects were inhibited by the autophagy-specific inhibitor, 3-Methyladenine (3 MA). Moreover the effects of PGN were caspase-3 independent. These preliminary
results suggest that PGN is able to induce atypical death of MC, probably by induction of an exacerbated autophagic response in a caspase-3-independent manner.
agonist) induced the production of several neurotoxic factors and cell death.
Our goal was to study the mechanisms responsible for the PGN-induced cell death. PGN promoted an increase in the frequency of annexin V/7-AAD double positive MC (late apoptotic/necrotic
cells), after 48 h of treatment (81% vs 7%, p<0,0001), without the presence of annexin V single positive cells (early apoptotic cells) at any time point.
In addition, BV2 cells stimulated with PGN showed, by electronic microscopy, the presence of double membrane vesicles (compatible with the ultrastructure of autophagic vesicles) and strong
vacuolization in the cell cytoplasm. These findings correlated with both a particulated pattern of cytoplasmic staining with monodansylcadaverine (MDC), and detection of increased cleaved LC3B
(LC3B II) by western blot. These effects were inhibited by the autophagy-specific inhibitor, 3-Methyladenine (3 MA). Moreover the effects of PGN were caspase-3 independent. These preliminary
results suggest that PGN is able to induce atypical death of MC, probably by induction of an exacerbated autophagic response in a caspase-3-independent manner.
