Adenosine-induced expression of interleukin-6 in astrocytes through protein kinase A and NF-IL-6
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 signa...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
15 May 2000
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| In: |
Glia
Year: 2000, Volume: 31, Issue: 1, Pages: 51-58 |
| ISSN: | 1098-1136 |
| DOI: | 10.1002/(SICI)1098-1136(200007)31:1<51::AID-GLIA50>3.0.CO;2-M |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/(SICI)1098-1136(200007)31:1<51::AID-GLIA50>3.0.CO;2-M Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/%28SICI%291098-1136%28200007%2931%3A1%3C51%3A%3AAID-GLIA50%3E3.0.CO%3B2-M 
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| Author Notes: | Markus Schwaninger, Nicole Petersen, Simone Prinz, Svea Sallmann, Mike Neher, and Matthias Spranger |
| Summary: | 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. |
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| Item Description: | Gesehen am 01.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1098-1136 |
| DOI: | 10.1002/(SICI)1098-1136(200007)31:1<51::AID-GLIA50>3.0.CO;2-M |