Abstract
BackgroundNeuropeptide 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.MethodsThe 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.ResultsHere, 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.ConclusionsAltogether, we have identified a novel role for NPY in the regulation of microglial phagocytic properties, in an inflammatory context.
Highlights
Neuropeptide Y (NPY) is emerging as a modulator of communication between the brain and the immune system
LPS is a component of Gram-negative bacterial outer membranes and binds to the CD14/Toll-like receptor 4 (TLR4)/MD2 receptor complex present at the microglial cell membrane, triggering several signaling cascades [15]
We focused on the role of NPY on Fc receptor-mediated phagocytosis, the main phagocytic process occurring in macrophages, a cell type that shares close functional and morphological resemblances to microglia
Summary
Neuropeptide Y (NPY) is emerging as a modulator of communication between the brain and the immune system. 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. Growing evidence supports involvement of neuropeptide Y (NPY) in the modulation of the immune system, with effects on macrophage, B and T cell function; as well as dendritic cell stimulatory ability [10]. Neuropeptide Y (NPY) is widely distributed within the peripheral and central nervous systems and has well defined physiological roles that include regulation of blood pressure, circadian rhythms, feeding behavior, memory processing and learning [11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
