Cyclic AMP and tumor necrosis factor-alpha regulate CXCR4 gene expression in Schwann cells.
Rat peripheral nerve Schwann cells have been shown to express the alpha-chemokine receptor CXCR4 as well as the corresponding ligand stromal cell-derived factor-1 (SDF-1). We have investigated gene regulatory mechanisms acting on the expression of CXCR4 in cultured rat Schwann cells and found that receptor expression at transcript- and protein levels is directly dependent on intracellular cyclic AMP. Such increased levels of CXCR4 expression were found to be efficiently reversed by the action of tumor necrosis factor-alpha (TNFalpha). We also provide evidence that the POU box transcription factor Oct-6/SCIP is involved in the control of CXCR4 transcription. Finally, we could demonstrate that CXCR4 activation by SDF-1alpha increases the number of dying Schwann cells, indicating that this receptor/ligand interaction is modulating cell survival. Our data, therefore, suggest that in the Schwann cell lineage signal transduction cascades controlled by the activation of TNF- and CXCR4 receptors are functionally coupled.
Küry
Patrick
P
Department of Neurology, Molecular Neurobiology Laboratory, Heinrich-Heine University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany. kuery@uni-duesseldorf.de
Köller
Hubertus
H
Hamacher
Michael
M
Cornely
Christiane
C
Hasse
Birgit
B
Müller
Hans Werner
HW
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D050816:Octamer Transcription Factor-6; D010525:Peripheral Nerves / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D019707:Receptors, Chemokine; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C486264:Cxcr4 protein, rat; C494179:Pou3f1 protein, rat; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D050816:Octamer Transcription Factor-6; D000242:Cyclic AMP