Aß potentiates inflammatory activation of glial cells induced by scavenger receptor ligands and inflammatory mediators in culture.

Alzheimer disease (AD) is a neurodegenerative disorder characterized by the accumulation of ß amyloid (Aß) aggregates. Aß induces the inflammatory activation of glia, inducing secretion of Interleukin 1ß (IL1ß), nitric oxide (NO) and superoxide radicals. The specific receptor responsible for the induction of inflammatory activation by Aß, is still an open question. We propose that scavenger receptors (SR) participate in the activation of glia by Aß. We assessed production of NO, synthesis of IL1ß and activation of ERK, JNK and NF-κB signaling pathways by Western blot, in primary rat glial cultures exposed to SR ligands (fucoidan and Poly I), LPS + IFNγ (LI), and Aß. Poly I but not fucoidan nor fibrillar Aß increased threefold NO production by astrocytes in a time-dependent manner. Fucoidan and Poly I increased 5.5- and 3.5-fold NO production by microglia, and co-stimulation with Aß increased an additional 60% NO induced by SR ligands. Potentiation by Aß was observed later for astrocytes than for microglia. In astrocytes, co-stimulation with Aß potentiated ERK and JNK activation in response to Fucoidan and Poly I, whereas it reduced induction of JNK activation by LI and left unaffected NF-κB activation induced by LI. Levels of pro-IL1ß in astrocytes increased with Aß, SR ligands and LI, and were potentiated by co-stimulation with Aß. Our results suggest that SRs play a role on inflammatory activation, inducing production of NO and IL1ß, and show potentiation by Aß. Potentiation of the inflammatory response of Aß could be meaningful for the activation of glia observed in AD.