INVESTIGADORES
IRIBARREN Pablo
congresos y reuniones científicas
Título:
Modulation of Microglial Cells Survival by IL4: Targeting the Neuroinflammation
Autor/es:
SORIA, JA; ARROYO, DS; GAVIGLIO, EA; IRIBARREN, P
Reunión:
Congreso; First French-Argentine Immunology Congress; 2010
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:
Microglial cells (MC) are the
brain-resident immune cells. After acute activation, as a result of neuronal
injury, MC proliferates, change their morphology (reactive microgliosis) and
secrete neurotoxic factors. The activities of these cells are mostly
beneficial, becoming destructive only when they escape from the strict control
normally made by the Central Nervous System (CNS) envirnment. Downregulation of
inflammatory mediators and removal of activated microglia may be key underlying
mechanisms by which brain inflammation is controlled. Furthermore,
anti-inflammatory cytokines, such as IL-4 and IL-13, may participate in these
regulatory mechanisms present in the CNS. Therefore, we evaluated the effects
of IL-4 on MC survival.
Here, we show that IL4 induced
a significant increase in the apoptosis of N9 microglial cells after 48 h
of culture (hypodiploid DNA content, p = 0.0001). IL4 also increased the
percentage of annexin-V single positive and annexin-V/7AAD double positive
cells, indicating induction of early and late apoptosis respectively. In addition,
we found that IL4 significantly increased the cleavage of caspase 3 (p
<0.01). Moreover, the IL-4-induced cell death was blocked by the presence of
a clasical pan caspase inhibitor zVAD (p <0.05). We also determined that
caspase 3 was not only cleaved but also activated, by detection of cleaved PARP
in IL-4-stimulated cells. PARP is one of the specific substrates of caspase 3
and a critical factor involved in DNA repair to prevent apoptosis. In another
set of experiments we observed that IL-4 was able to reduce the levels of
Bcl-XL (western blot) and constitutive authophagy (microscopy, MDC staining),
two factors related to cell survival.
Our preliminary results
suggest that induction of MC death may be an additional mechanism induced by
IL4 to control the extent and duration of neuroinflammation.