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

<p>Abstract</p> <p>Background</p> <p>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 inflamm...

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Main Authors: Ferreira Raquel, Santos Tiago, Viegas Michelle, Cortes Luísa, Bernardino Liliana, Vieira Otília V, Malva João O
Format: Article
Language:English
Published: BMC 2011-12-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:http://www.jneuroinflammation.com/content/8/1/169
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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 DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 <it>via </it>Y<sub>1 </sub>receptor activation.</p> <p>Conclusions</p> <p>Altogether, we have identified a novel role for NPY in the regulation of microglial phagocytic properties, in an inflammatory context.</p>
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spelling doaj.art-f38cb916b3c5446ca45467579c2e263c2022-12-21T20:55:54ZengBMCJournal of Neuroinflammation1742-20942011-12-018116910.1186/1742-2094-8-169Neuropeptide Y inhibits interleukin-1β-induced phagocytosis by microglial cellsFerreira RaquelSantos TiagoViegas MichelleCortes LuísaBernardino LilianaVieira Otília VMalva João O<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 <it>via </it>Y<sub>1 </sub>receptor activation.</p> <p>Conclusions</p> <p>Altogether, we have identified a novel role for NPY in the regulation of microglial phagocytic properties, in an inflammatory context.</p>http://www.jneuroinflammation.com/content/8/1/169microglianeuropeptide YHSP27p38inflammationphagocytic cups
spellingShingle 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
Journal of Neuroinflammation
microglia
neuropeptide Y
HSP27
p38
inflammation
phagocytic cups
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 microglia
neuropeptide Y
HSP27
p38
inflammation
phagocytic cups
url http://www.jneuroinflammation.com/content/8/1/169
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