CHARACTERIZATION OF TREM -2 EXPRESSION PROFILE AND ROLE IN EXPERIMENTAL BRAIN ISCHEMIA

CADENA V; ROSCISZEWSKI G; RAMOS AJ

Buenos Aires

Congreso; LXI meeting de la Sociedad Argentina de Investigacion Clínica (SAIC); 2016

Sociedad Argentina de Investigacion Clinica - Sociedad Argentina de Inmunología

After brain injury, DAMP are released from necrotic cells andactivate toll-like receptors (TLR) in professional innate immunity cells and astrocytes. Astrocytes respond to the injury with a typicalphenomenon known as reactive gliosis, and thereafter they canpolarize towards a proinflammatory phenotype that induces neurodegeneration.The mechanisms leading to the proinflammatoryneurodegenerativeglial profile are unknown but evidences are indicatingthat overactivation of TLR and downstream NFkB signalingcan be involved. TREM-2 and its adaptor DAP12 down-regulateTLR signaling, and thus it is proposed to participate in the finetuningof the inflammatory response in professional immune cells.Using an experimental model of focal brain ischemia by unilateralcortical devascularization and astroglial-enriched cell culture, westudied here the expression of TREM-2 and the cellular consequencesof its activation. We observed that TREM-2 is expressedprimarily in microglia, but also in penumbral astrocytes after brainischemia. In vitro, TREM-2 is expressed in rat astrocytes-enrichedcell cultures exposed to hypoxia or oxygen-glucose deprivation(OGD, in vitro model of ischemia) but also facilitated by PAMP(LPS) or DAMP (HMGB-1) treatment. Further, we transfectedastrocytes and overexpressed TREM-2 and DAP12 and observedthat TREM-2 overexpressing astrocytes show reduced NFkB acti -vation after LPS exposure. We conclude that TREM-2 representsan interesting target to limit the astroglial response to inflammatoryclues and to prevent the conversion to the proinflammatoryneurodegenerative phenotype.