Neuropeptide Y inhibits interleukin-1 beta-induced microglia motility.
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.
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Raquel
R
Ferreira
Tiago
T
Santos
Luísa
L
Cortes
Stéphanie
S
Cochaud
Fabienne
F
Agasse
Ana Paula
AP
Silva
Sara
S
Xapelli
João O
JO
Malva
D000818:Animals; D015153:Blotting, Western; D039481:CD11b Antigen / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D003627:Data Interpretation, Statistical; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects*; D009478:Neuropeptide Y / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D039481:CD11b Antigen; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D048051:p38 Mitogen-Activated Protein Kinases