Adenosine-induced expression of interleukin-6 in astrocytes through protein kinase A and NF-IL-6

• Verfasst von: Schwaninger, Markus [VerfasserIn]
• Verfasst von: Petersen, Nicole [VerfasserIn]
• Verfasst von: Prinz, Simone [VerfasserIn]
• Verfasst von: Sallmann, Svea [VerfasserIn]
• Verfasst von: Neher, Michael [VerfasserIn]
• Verfasst von: Spranger, Matthias [VerfasserIn]
• Titel: Adenosine-induced expression of interleukin-6 in astrocytes through protein kinase A and NF-IL-6
• Verf.angabe: Markus Schwaninger, Nicole Petersen, Simone Prinz, Svea Sallmann, Mike Neher, and Matthias Spranger
• E-Jahr: 2000
• Jahr: 15 May 2000
• Umfang: 8 S.
• Teil: volume:31
• Teil: year:2000
• Teil: number:1
• Teil: pages:51-58
• Teil: extent:8
• Fussnoten: Gesehen am 01.04.2021
• Titel Quelle: Enthalten in: Glia
• Ort Quelle: Bognor Regis [u.a.] : Wiley-Liss, 1988
• Jahr Quelle: 2000
• Band/Heft Quelle: 31(2000), 1, Seite 51-58
• ISSN Quelle: 1098-1136
• DOI: doi:10.1002/(SICI)1098-1136(200007)31:1<51::AID-GLIA50>3.0.CO;2-M
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: adenosine
• Sach-SW: astrocytes
• Sach-SW: IL-6
• Sach-SW: NF-IL-6
• K10plus-PPN: 1753112044

Abstract

In various neurologic diseases, astrocytes express interleukin-6 (IL-6), which is an endogenous pyrogen, a neuroprotective factor, and a regulator of the blood-brain barrier. The expression of IL-6 in astrocytes is stimulated by extracellular adenosine through A2B receptors. To investigate the signaling cascade that induces IL-6 gene transcription further, we transfected primary mouse astrocytes with a reporter gene construct, in which luciferase expression is directed by the human IL-6 promoter. Expression of PKI, an inhibitor of protein kinase A (PKA), interfered with IL-6 transcription indicating that PKA mediates the effect of adenosine. The CAAT box of the IL-6 promoter is necessary for the stimulation by adenosine as a mutation in this element reduced the stimulation by adenosine. Indeed, the cAMP agonist forskolin increased the binding of the transcription factors NF-IL-6 and C/EBPδ to the CAAT box of the IL-6 promoter in nuclear extracts of astrocytes. Inhibition of the de novo synthesis of NF-IL-6 by cycloheximide or an antisense oligonucleotide reduced the enhancement of NF-IL-6 binding to the CAAT box and inhibited stimulation of IL-6 transcription by forskolin. In addition, overexpression of NF-IL-6 induced IL-6 transcription. This suggests that adenosine induces the de novo synthesis of NF-IL-6 through activation of PKA and thereby stimulates transcription of IL-6 in astrocytes. GLIA 31:51-58, 2000. © 2000 Wiley-Liss, Inc.