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SR-A Regulates the Inflammatory Activation of Astrocytes

Neurotoxicity Research volume 25, pages 68–80 (2014)Cite this article

Abstract

Scavenger receptor Class A (SR-A) participates in the regulation of inflammatory processes against pathogens and in inflammatory stimulation. We have recently demonstrated the presence of SR-A in astrocytes, but its participation in their inflammatory response is unknown. Astrocytes regulate neuroinflammation through the regulation of microglial cell activation and the production of cytokines, neurotrophic factors, and reactive species. Using astrocytes from SR-A−/− mice in culture, we assessed the participation of SR-A in their inflammatory activation, evaluating the activation of IκB/NF-κB and MAPK signaling pathways and the production of nitric oxide (NO) and IL-1β in response to SR-A ligands. In SR-A−/− astrocytes, lipopolysaccharide (LPS) induced higher levels of NO and reduced levels of IL-1β compared to SR-A+/+ cells. In addition, SR-A−/− astrocytes had a reduced basal and LPS-stimulated JNK phosphorylation, and a delayed activation on IκB/NF-κB signaling pathway in response to LPS. Moreover, inhibition of the ERK pathway reduced NO production by SR-A−/− cells, suggesting that this signaling pathway modulated LPS-induced NO production, an effect that depended on the presence of SR-A. Our results suggest that SR-A participates in the modulation of signaling pathways involved in the production of soluble molecules implicated in the neuroinflammatory response.

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Acknowledgments

This work was supported by grant FONDECYT 1131025. We thank Dr. Dagoberto Soto and Dr. Juan Tichauer for technical help. We thank Dr. Kodama (Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan) for the SR-A−/− and SR-A+/+ mice in the 129/ICR background.

Conflict of interest

The authors declare that they have no conflicts of interest.

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  1. Departamento de Neurología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile

    P. Murgas, F. A. Cornejo, G. Merino & R. von Bernhardi

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  1. P. Murgas
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  2. F. A. Cornejo
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  3. G. Merino
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  4. R. von Bernhardi
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Corresponding author

Correspondence to R. von Bernhardi.

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P. Murgas and F. A. Cornejo contributed equally to this study.

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12640_2013_9432_MOESM1_ESM.tif

Supplementary Figure 1 SR-A deletion does not alter TLR4 expression. TLR4 protein expression was observed by Western blot for SR-A+/+ and SR-A−/− astrocytes in control and LPS-stimulated conditions from 24 to 72 h. GAPDH protein was used as a load control

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Murgas, P., Cornejo, F.A., Merino, G. et al. SR-A Regulates the Inflammatory Activation of Astrocytes. Neurotox Res 25, 68–80 (2014). https://doi.org/10.1007/s12640-013-9432-1

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Keywords

  • Astrocytes
  • IL-1β
  • Neuroinflammation
  • Nitric oxide
  • SR-A