Interleukin 4 induces the apoptosis of mouse microglial cells by a caspase-dependent mechanism.

SORIA, JA; ARROYO, DS; GAVIGLIO, EA; WANG, JM; RODRIGUEZ-GALAN, MC; IRIBARREN, P

NEUROBIOLOGY OF DISEASE

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2011

0969-9961

Microglial cells are resident macrophages in the central nervous system (CNS) and becomeactivated in many pathological conditions. Activation of microglial cells results in reactivemicrogliosis, manifested by an increase in cell number in the affected CNS regions. Thecontrol of microgliosis may be important to prevent pathological damage to the brain. Thetype 2 cytokine IL-4 has been reported to be protective in brain inflammation. However, itseffect on microglial cell survival was not well understood. In this study, we report a dualeffect of IL-4 on the survival of mouse microglial cells. In a 6 h short term culture, IL-4reduced the death of microglial cells induced by staurosporine. In contrast, in long termtreatment (more than 48 h), IL-4 increased the apoptotic death of both primary mousemicroglial cells and a microglial cell line N9. Mechanistic studies revealed that, inmicroglial cells, IL-4 increased the levels of cleaved caspase 3 and PARP, which is downstreamof activated caspase 3. In addition, IL-4 down regulated the autophagy and theantiapoptotic protein Bcl-xL in microglial cells. On the other hand, the pre-incubation ofmicroglial cells with IL-4 for 24 h, attenuated the cell death induced by the neurotoxicpeptide amyloid beta 1-42 (Abeta42). Our observations demonstrate a novel function of IL-4in regulating the survival of microglial cells, which may have important significance inreduction of undesired inflammatory responses in the CNS.