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Aβ Potentiates Inflammatory Activation of Glial Cells Induced by Scavenger Receptor Ligands and Inflammatory Mediators in Culture

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Abstract

Alzheimer disease (AD) is a neurodegenerative disorder characterized by the accumulation of β amyloid (Aβ) aggregates. Aβ induces the inflammatory activation of glia, inducing secretion of Interleukin 1β (IL1β), nitric oxide (NO) and superoxide radicals. The specific receptor responsible for the induction of inflammatory activation by Aβ, is still an open question. We propose that scavenger receptors (SR) participate in the activation of glia by Aβ. We assessed production of NO, synthesis of IL1β 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 Aβ. Poly I but not fucoidan nor fibrillar Aβ 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 Aβ increased an additional 60% NO induced by SR ligands. Potentiation by Aβ was observed later for astrocytes than for microglia. In astrocytes, co-stimulation with Aβ 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-IL1β in astrocytes increased with Aβ, SR ligands and LI, and were potentiated by co-stimulation with Aβ. Our results suggest that SRs play a role on inflammatory activation, inducing production of NO and IL1β, and show potentiation by Aβ. Potentiation of the inflammatory response of Aβ could be meaningful for the activation of glia observed in AD.

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Acknowledgment

This work was supported by grant Fondecyt 1090353 to Dr. R. von Bernhardi.

Conflict of interest

Authors (PM, BG and RvB) declare they have no conflict of interest.

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  1. Laboratory of Neuroscience, Department of Neurology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile

    P. Murgas, B. Godoy & R. von Bernhardi

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  1. P. Murgas
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  2. B. Godoy
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  3. R. von Bernhardi
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Correspondence to R. von Bernhardi.

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P. Murgas and B. Godoy have contributed equally to this work.

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Murgas, P., Godoy, B. & von Bernhardi, R. Aβ Potentiates Inflammatory Activation of Glial Cells Induced by Scavenger Receptor Ligands and Inflammatory Mediators in Culture. Neurotox Res 22, 69–78 (2012). https://doi.org/10.1007/s12640-011-9306-3

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