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Published on: July 25, 2022
Neuropeptide Y inhibits interleukin-1 beta-induced microglia motility
Raquel Ferreira1, Tiago Santos, Luísa Cortes
1Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Abstract:
Increasing evidences suggest that neuropeptide Y (NPY) may act as a key modulator of the cross-talk between the brain and the immune system in health and disease. In the present study, we dissected the possible inhibitory role of NPY upon inflammation-associated microglial cell motility. NPY, through activation of Y(1) receptors, was found to inhibit lipopolysaccharide (LPS)-induced microglia (N9 cell line) motility. Moreover, stimulation of microglia with LPS was inhibited by IL-1 receptor antagonist (IL-1ra), suggesting the involvement of endogenous interleukin-1 beta (IL-1β) in this process. Direct stimulation with IL-1β promoted downstream p38 mitogen-activated protein kinase mobilization and increased microglia motility. Moreover, consistently, p38 mitogen-activated protein kinase inhibition decreased the extent of actin filament reorganization occurring during plasma membrane ruffling and p38 phosphorylation was inhibited by NPY, involving Y(1) receptors. Significantly, the key inhibitory role of NPY on LPS-induced motility of CD11b-positive cells was further confirmed in mouse brain cortex explants. In summary, we revealed a novel functional role for NPY in the regulation of microglial function that may have important implications in the modulation of CNS injuries/diseases where microglia migration/motility might play a role.
Insights
Neuropeptide Y (NPY) inhibits inflammation-driven microglial cell movement by blocking interleukin-1 beta (IL-1β) signaling via Y(1) receptors. This finding is crucial for understanding central nervous system (CNS) injury and disease modulation.
Area of Science:
- Neuroimmunology
- Cellular Neuroscience
Background:
- Neuropeptide Y (NPY) is increasingly recognized for its role in brain-immune system interactions.
- Microglial cell motility is implicated in central nervous system (CNS) pathologies.
- Understanding the regulation of microglial function is critical for developing therapeutic strategies.
Purpose of the Study:
- To investigate the inhibitory role of NPY on inflammation-associated microglial cell motility.
- To elucidate the signaling pathways involved in NPY-mediated regulation of microglial function.
Main Methods:
- Utilized N9 microglial cell line and mouse brain cortex explants.
- Assessed microglial motility using lipopolysaccharide (LPS) and interleukin-1 beta (IL-1β) stimulation.
- Investigated the involvement of Y(1) receptors, IL-1 receptor antagonist (IL-1ra), and p38 mitogen-activated protein kinase (MAPK) signaling.
Main Results:
- NPY, via Y(1) receptors, inhibited LPS-induced microglial motility.
- IL-1β signaling pathway, including p38 MAPK activation, was involved in promoting microglial motility.
- NPY inhibited IL-1β-induced p38 MAPK phosphorylation and downstream effects on actin reorganization.
Conclusions:
- NPY exerts an inhibitory effect on microglial cell motility, particularly in response to inflammatory stimuli.
- The mechanism involves the modulation of the IL-1β/p38 MAPK signaling pathway.
- NPY's role in regulating microglial function has significant implications for CNS injuries and diseases involving microglial migration.
