IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Dual actions of HMGB-1 on neuroinflammation are dependent on the cellular micro-environment
Autor/es:
LUKIN J, ROSCISEWSKI G, MURTA V, CADENA MV, VILLARREAL A, RAMOS AJ
Lugar:
Mar del Plata, Argentina
Reunión:
Congreso; XXX Congreso de la Sociedad Argentina de Investigacion en Neurociencias (SAN); 2015
Resumen:
Brain injury produces a release of DAMP (Damage Associated Molecular Patterns) from thelesion core to the extracellular space activating brain innate immunity. The protein HMGB-1 is a main DAMP discharged by necrotic neurons and it is proposed to signalize throughreceptors TLR-2, TLR-4 and RAGE to induce an inflammatory response mediated byastrocytes and microglia.In this work, we used an in vitro approach to study the role of HMGB-1 in reactive gliosisand to analyze the astroglial-microglial interaction. In hippocampal mixed neuro-gliaculture containing all glial types and neurons, HMGB-1 induced neurodegeneration andastroglial conversion into a fibrillar reactive phenotype. Using astrocytes-enriched culture,we revealed that HMGB-1 activates the inflammatory transcriptional factor NF-kB in a timeand concentration-dependent manner. When we dissected the HMGB-1 effects on thedifferent cell types using conditioned media we observed that astrocytes exposed toHMGB-1 released factors induce microglial conversion to a mixed microglia M1/M2activation profile. However, on neurons cultures, direct HMBG-1 application did notdramatically affected neuronal survival whereas conditioned media from astrocytesexposed to HMGB-1 increased neuronal survival. Based on these experiments, we concludethat HMGB-1 released by necrotic neurons after brain injury may have either aneurodegenerative or protective effect depending on the cellular micro-environmentwhere it is released.