Neurotrophins regulate the function of cultured microglia.
Although the physiological role of neurotrophins in neuronal development and survival has been extensively investigated, their role in glial cell physiology remains to be elucidated. In the present study, we investigated the effects of neurotrophins on cultured microglia from newborn rat brain. All of the neurotrophins tested nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), increased the secretion of plasminogen and urokinase type-plasminogen activator and specific activity of acid phosphatase, but suppressed the release of constitutively-produced and lipopolysaccharide-stimulated nitric oxide (NO) from microglia. The reverse transcription-polymerase chain reaction, immunocytochemical staining, and Western blotting revealed that cultured microglia express Trk A, B, and C, and low-affinity NGF receptor, LNGFRp75. Neurotrophin was found to phosphorylate Trk A and B, and the neurotrophin-induced enhancement of plasminogen-secretion was suppressed by protein kinase inhibitor, K252a. Furthermore, neurotrophins caused an activation of transcription factor, NF-kappaB. These results indicate that the neurotrophin family regulate the function of microglia through Trk and/or LNGFRp75-mediated signal transduction.
Department of Neurochemistry, National Institute of Neuroscience, Kodaira, Tokyo, Japan.
K
K
Nakajima
Y
Y
Kikuchi
E
E
Ikoma
S
S
Honda
M
M
Ishikawa
Y
Y
Liu
S
S
Kohsaka
D015720:5'-Nucleotidase / Q000378:metabolism; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015139:Blotting, Southern; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D017628:Microglia / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009414:Nerve Growth Factors / Q000502:physiology*; D020933:Neurotrophin 3; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D010958:Plasminogen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; D016328:NF-kappa B; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D009569:Nitric Oxide; D010958:Plasminogen; D020794:Receptor Protein-Tyrosine Kinases; D000135:Acid Phosphatase; D015720:5'-Nucleotidase; D014568:Urokinase-Type Plasminogen Activator; C073922:neurotrophin 4