Efeitos dos glicocorticoides nas interações celulares de astrócitos, microglia e neurônios durante inflamação induzida por LPS em modelo >i<in vitro>/i<.

Abstract

The proper functioning of the neuron-microglia-astrocyte triad is fundamental for the maintenance of central nervous system (CNS), since neurodegenerative and aging processes may be related to a "defective" cellular interaction between neurons and glia. Activation and recruitment of glial cells are complex processes and require well-organized intercommunication between neurons and glial cells as well as between glial cells. Despite the well-established anti-inflammatory effect of glucocorticoids (GCs), it has been shown that, in the CNS, increased levels of this hormone may potentiate some aspects of the inflammatory response, for example the activation of the lipopolysaccharide-induced NFKB transcription factor and the evidence pointing to the cellular specificity of these actions is increasing. This study aims to characterize the effects of GCs on physical and humoral cellular interactions between astrocytes, microglia, and neurons in the presence of an acute inflammatory stimulus, LPS, in in vitro primary cell cultures derived from the brain cortex of neonatal rats. We verified that GCs are not anti-inflammatory since they do not decrease the activation of NFKB and yet potentiate the LPS-induced cell death in mixed cultures. Astrocytes in mixed, neuron-and astrocyte-enriched cultures have different responses to LPS, as well as previous treatment with GCs, regarding the nuclear localization of RELA, an indication of its activation. Our results in this cell type suggest that GCs are proinflammatory and this action seems to depend on cell interactions and the presence of GR / MR heterodimers. Microglia participates in the response of astrocytes to LPS in relation to the nuclear localization of RELA.