Abstract
Following peripheral nerve transection, CX3CR1 and TGF-beta1 are increased in a time-dependent manner within the injured facial motor nucleus. To explore the relationship between TGF-beta1 and CX3CR1 in the CNS, the effects of TGF-beta1 on CX3CR1 mRNA, protein and fractalkine-dependent stimulation of signal transduction cascades in primary cultures of rat microglia were examined. TGF-beta1 increased steady state levels of CX3CR1 mRNA, 125I-fractalkine binding sites and blunted fractalkine-stimulated ERK1/2 phosphorylation. The half-life of CX3CR1 mRNA was unaltered by TGF-beta1 and two potential Smad binding elements (SBEs) were identified in the rat CX3CR1 promoter. TGF-beta1 may shift fractalkine-dependent signaling away from activation of ERK1/2 towards other pathways and/or may provide a mechanism for microglia to more strongly adhere to neurons.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Cells, Cultured
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Chemokine CX3CL1
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Chemokines, CX3C / immunology
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Chemokines, CX3C / metabolism*
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Chemokines, CX3C / pharmacology
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Dose-Response Relationship, Drug
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / immunology
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Membrane Proteins / immunology
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Membrane Proteins / metabolism*
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Membrane Proteins / pharmacology
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Microglia / drug effects
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Microglia / immunology
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Microglia / metabolism*
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Mitogen-Activated Protein Kinases / drug effects
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Mitogen-Activated Protein Kinases / immunology
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Mitogen-Activated Protein Kinases / metabolism
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Nerve Degeneration / immunology*
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Nerve Degeneration / physiopathology
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Interleukin-8A / drug effects
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Receptors, Interleukin-8A / genetics
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Receptors, Interleukin-8A / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / immunology
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Time Factors
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Transcription, Genetic / drug effects
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Transcription, Genetic / immunology
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Transforming Growth Factor beta / immunology
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Transforming Growth Factor beta / metabolism*
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Transforming Growth Factor beta / pharmacology
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Transforming Growth Factor beta1
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Up-Regulation / drug effects
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Up-Regulation / immunology*
Substances
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Chemokine CX3CL1
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Chemokines, CX3C
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Cx3cl1 protein, rat
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Membrane Proteins
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RNA, Messenger
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Receptors, Interleukin-8A
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Tgfb1 protein, rat
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Mitogen-Activated Protein Kinases