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

Journal of Neuroinflammation

João O Malva²  Otília V Vieira¹  Liliana Bernardino¹  Luísa Cortes¹  Michelle Viegas¹  Tiago Santos¹  Raquel Ferreira¹ 

[1] Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal;Laboratory of Biochemistry and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

关键词: phagocytic cups;    inflammation;    p38;    HSP27;    neuropeptide Y;    microglia;   

Others  :  1212980
DOI  :  10.1186/1742-2094-8-169

 received in 2011-07-27, accepted in 2011-12-02,  发布年份 2011

【 摘 要 】

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 Y₁ receptor activation.

Conclusions

Altogether, we have identified a novel role for NPY in the regulation of microglial phagocytic properties, in an inflammatory context.

【 授权许可】

   
2011 Ferreira et al; licensee BioMed Central Ltd.

【 图 表 】

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