TGF-beta1 upregulates CX3CR1 expression and inhibits fractalkine-stimulated signaling in rat microglia.
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.
Chen
Shuzhen
S
Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610-0267, USA.
Luo
Defang
D
Streit
Wolfgang J
WJ
Harrison
Jeffrey K
JK
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009410:Nerve Degeneration / Q000276:immunology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D023062:Receptors, Interleukin-8A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D008565:Membrane Proteins; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D020928:Mitogen-Activated Protein Kinases