Aβ 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 beta amyloid (A beta) aggregates. A beta induces the inflammatory activation of glia, inducing secretion of Interleukin 1 beta (IL1 beta), nitric oxide (NO) and superoxide radicals. The specific receptor responsible for the induction of inflammatory activation by A beta, is still an open question. We propose that scavenger receptors (SR) participate in the activation of glia by A beta. We assessed production of NO, synthesis of IL1 beta and activation of ERK, JNK and NF-kappa B signaling pathways by Western blot, in primary rat glial cultures exposed to SR ligands (fucoidan and Poly I), LPS + IFN gamma (LI), and A beta. Poly I but not fucoidan nor fibrillar A beta 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 A beta increased an additional 60% NO induced by SR ligands. Potentiation by A beta was observed later for astrocytes than for microglia. In astrocytes, co-stimulation with A beta 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-kappa B activation induced by LI. Levels of pro-IL1 beta in astrocytes increased with A beta, SR ligands and LI, and were potentiated by co-stimulation with A beta. Our results suggest that SRs play a role on inflammatory activation, inducing production of NO and IL1 beta, and show potentiation by A beta. Potentiation of the inflammatory response of A beta could be meaningful for the activation of glia observed in AD.