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Neuropeptide Y inhibits interleukin-1β-induced phagocytosis by microglial cells

BACKGROUND: Neuropeptide Y (NPY) is emerging as a modulator of communication between the brain and the immune system. However, in spite of increasing evidence that supports a role for NPY in the modulation of microglial cell responses to inflammatory conditions, there is no consistent information re...

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Autores principales: Ferreira, Raquel, Santos, Tiago, Viegas, Michelle, Cortes, Luísa, Bernardino, Liliana, Vieira, Otília V, Malva, João O
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3239417/
https://www.ncbi.nlm.nih.gov/pubmed/22136135
http://dx.doi.org/10.1186/1742-2094-8-169
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author Ferreira, Raquel
Santos, Tiago
Viegas, Michelle
Cortes, Luísa
Bernardino, Liliana
Vieira, Otília V
Malva, João O
author_facet Ferreira, Raquel
Santos, Tiago
Viegas, Michelle
Cortes, Luísa
Bernardino, Liliana
Vieira, Otília V
Malva, João O
author_sort Ferreira, Raquel
collection PubMed
description BACKGROUND: Neuropeptide Y (NPY) is emerging as a modulator of communication between the brain and the immune system. However, in spite of increasing evidence that supports a role for NPY in the modulation of microglial cell responses to inflammatory conditions, there is no consistent information regarding the action of NPY on microglial phagocytic activity, a vital component of the inflammatory response in brain injury. Taking this into consideration, we sought to assess a potential new role for NPY as a modulator of phagocytosis by microglial cells. METHODS: The N9 murine microglial cell line was used to evaluate the role of NPY in phagocytosis. For that purpose, an IgG-opsonized latex bead assay was performed in the presence of lipopolysaccharide (LPS) and an interleukin-1β (IL-1β) challenge, and upon NPY treatment. A pharmacological approach using NPY receptor agonists and antagonists followed to uncover which NPY receptor was involved. Moreover, western blotting and immunocytochemical studies were performed to evaluate expression of p38 mitogen-activated protein kinase (MAPK) and heat shock protein 27 (HSP27), in an inflammatory context, upon NPY treatment. RESULTS: Here, we show that NPY inhibits phagocytosis of opsonized latex beads and inhibits actin cytoskeleton reorganization triggered by LPS stimulation. Co-stimulation of microglia with LPS and adenosine triphosphate also resulted in increased phagocytosis, an effect inhibited by an interleukin-1 receptor antagonist, suggesting involvement of IL-1β signaling. Furthermore, direct application of LPS or IL-1β activated downstream signaling molecules, including p38 MAPK and HSP27, and these effects were inhibited by NPY. Moreover, we also observed that the inhibitory effect of NPY on phagocytosis was mediated via Y(1 )receptor activation. CONCLUSIONS: Altogether, we have identified a novel role for NPY in the regulation of microglial phagocytic properties, in an inflammatory context.
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spelling pubmed-32394172011-12-16 Neuropeptide Y inhibits interleukin-1β-induced phagocytosis by microglial cells Ferreira, Raquel Santos, Tiago Viegas, Michelle Cortes, Luísa Bernardino, Liliana Vieira, Otília V Malva, João O J Neuroinflammation Research BACKGROUND: Neuropeptide Y (NPY) is emerging as a modulator of communication between the brain and the immune system. However, in spite of increasing evidence that supports a role for NPY in the modulation of microglial cell responses to inflammatory conditions, there is no consistent information regarding the action of NPY on microglial phagocytic activity, a vital component of the inflammatory response in brain injury. Taking this into consideration, we sought to assess a potential new role for NPY as a modulator of phagocytosis by microglial cells. METHODS: The N9 murine microglial cell line was used to evaluate the role of NPY in phagocytosis. For that purpose, an IgG-opsonized latex bead assay was performed in the presence of lipopolysaccharide (LPS) and an interleukin-1β (IL-1β) challenge, and upon NPY treatment. A pharmacological approach using NPY receptor agonists and antagonists followed to uncover which NPY receptor was involved. Moreover, western blotting and immunocytochemical studies were performed to evaluate expression of p38 mitogen-activated protein kinase (MAPK) and heat shock protein 27 (HSP27), in an inflammatory context, upon NPY treatment. RESULTS: Here, we show that NPY inhibits phagocytosis of opsonized latex beads and inhibits actin cytoskeleton reorganization triggered by LPS stimulation. Co-stimulation of microglia with LPS and adenosine triphosphate also resulted in increased phagocytosis, an effect inhibited by an interleukin-1 receptor antagonist, suggesting involvement of IL-1β signaling. Furthermore, direct application of LPS or IL-1β activated downstream signaling molecules, including p38 MAPK and HSP27, and these effects were inhibited by NPY. Moreover, we also observed that the inhibitory effect of NPY on phagocytosis was mediated via Y(1 )receptor activation. CONCLUSIONS: Altogether, we have identified a novel role for NPY in the regulation of microglial phagocytic properties, in an inflammatory context. BioMed Central 2011-12-02 /pmc/articles/PMC3239417/ /pubmed/22136135 http://dx.doi.org/10.1186/1742-2094-8-169 Text en Copyright ©2011 Ferreira et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Ferreira, Raquel
Santos, Tiago
Viegas, Michelle
Cortes, Luísa
Bernardino, Liliana
Vieira, Otília V
Malva, João O
Neuropeptide Y inhibits interleukin-1β-induced phagocytosis by microglial cells
title Neuropeptide Y inhibits interleukin-1β-induced phagocytosis by microglial cells
title_full Neuropeptide Y inhibits interleukin-1β-induced phagocytosis by microglial cells
title_fullStr Neuropeptide Y inhibits interleukin-1β-induced phagocytosis by microglial cells
title_full_unstemmed Neuropeptide Y inhibits interleukin-1β-induced phagocytosis by microglial cells
title_short Neuropeptide Y inhibits interleukin-1β-induced phagocytosis by microglial cells
title_sort neuropeptide y inhibits interleukin-1β-induced phagocytosis by microglial cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3239417/
https://www.ncbi.nlm.nih.gov/pubmed/22136135
http://dx.doi.org/10.1186/1742-2094-8-169
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