Triggering Receptor Expressed on Myeloid cells-2 (TREM-2) expression is induced by brain ischemia and DAMPs.

CADENA V, ROSCISZEWSKI G, LUKIN J, MURTA V, ROSSI A, RAMOS AJ

Mar del Plata

Congreso; XXX Congreso de la Sociedad Argentina de Investigacion en Neurociencias (SAN; 2015

TREM-2 regulates toll-like receptors (TLR) signaling, and thus it is proposed to participate in the fine-tuning of the inflammatory response in professional immune cells like microglia. After brain injury DAMP are released from necrotic cells and activate TLR, but it is unknown whether DAMP or other molecules are TREM-2 ligands. Using an experimental model of focal brain ischemia by unilateral cortical devascularization and astroglial or microglia-enriched cell culture, we studied here the expression of TREM-2 and the cellular consequences of its activation. Our results showed that TREM-2 expression was induced in glial cells from the ischemic penumbra specifically in astrocytes and microglia at early time points after ischemia (3-7 days). In vitro, exposure to LPS or oxygen glucose deprivation also induced TREM-2 expression in astrocytes. The DAMP HMGB1 induced astroglial TREM-2 expression but failed to increase endogenous microglial TREM-2 expression. When TREM-2 was activated by antibody crosslinking in primary astrocytic culture, we observed a partial suppression of TLR-mediated LPS-induced NF-KB activation analyzed by the p65 subunit nuclear localization. We conclude that TREM-2 is expressed in glial cells in vivo after brain ischemia and in vitro. Astrocytes, not only express TREM-2, but also respond with the classical effect of limiting TLR-dependent NF-KB activity thus being an interesting target to limit reactive gliosis. Grants PICT 2012-1424, CONICET, UBACYT