Dual actions of HMGB1 on neuroinflammation are dependent on the cellular micro-environment

JERÓNIMO LUKIN; GERARDO ROSCISZEWSKI; VANESA CADENA; VERONICA MURTA; ALEJANDRO VILLARREAL; ALBERTO JAVIER RAMOS

Mar del Plata

Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2015

Sociedad Argentina de Investigación en Neurociencias

Brain injury produces a release of DAMP (Damage Associated MolecularPatterns) from the lesion core to the extracellular space activating brain innate immunity. The protein HMGB1 is one of the main DAMPs released from by necrotic neurons and it is proposed to signalize through receptors TLR-2, TLR-4 and RAGE. Downstream signaling of HMGB1 may lead to the activation of NF-κB,promoting the up-regulation of several pro-inflammatory cytokines inducing aninflammatory response called reactive gliosis, which is mediated by astrocytes and microglia. The diffusion of DAMP like HMGB1 from the lesion core to other regions of the brain may be responsible of the propagation and maintenance ofneuroinflammation. Even though, beneficial effects of HMGB1 had been describedat different situations after an insult. Understanding the mechanisms in which different DAMPs induce a glial response regulating the activation of brain innate immunity may be crucial for the development of future neuroprotective strategies.The aim of this work was to study the roles of HMGB-1 in reactive gliosis and neuroinflamation. To analyze the neuron-astroglial-microglial interaction after the exposure to this DAMP we performed in vitro experiments in neuroglial primary cultures, mixed-glial primary cultures, astrocyte-enriched cultures and microglia-enriched cultures.