Bradykinin induces interleukin-6 expression in astrocytes through activation of nuclear factor-κB
Bradykinin, a mediator of inflammation, is produced in the brain during trauma and stroke. It is thought to open the blood-brain barrier, although the mechanism is unclear. We have investigated, therefore, the effect of bradykinin on the expression of interleukin-6 (IL-6), a putative modulator of th...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
1999
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| In: |
Journal of neurochemistry
Year: 1999, Volume: 73, Issue: 4, Pages: 1461-1466 |
| ISSN: | 1471-4159 |
| DOI: | 10.1046/j.1471-4159.1999.0731461.x |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1046/j.1471-4159.1999.0731461.x Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1471-4159.1999.0731461.x 
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| Author Notes: | Markus Schwaninger, Svea Sallmann, Nicole Petersen, Armin Schneider, Simone Prinz, Towia A. Libermann, and Matthias Spranger |
| Summary: | Bradykinin, a mediator of inflammation, is produced in the brain during trauma and stroke. It is thought to open the blood-brain barrier, although the mechanism is unclear. We have investigated, therefore, the effect of bradykinin on the expression of interleukin-6 (IL-6), a putative modulator of the blood-brain barrier, in astrocytes. IL-6 gene transcription was evaluated by transient transfection of the human IL-6 promoter linked to the luciferase gene. In murine astrocytes, bradykinin stimulated IL-6 secretion and gene transcription. The effect of bradykinin was blocked by KN-93, an inhibitor of Ca2+/calmodulin-dependent protein kinases, and by bisindolyl-maleimide I, an inhibitor of protein kinase C, suggesting the involvement of these protein kinases. Mutations in the multiple response element and the binding site for nuclear factor-κB (NF-κB), but not in other known elements of the IL-6 promoter, interfered with induction of IL-6 transcription. The involvement of NF-κB was supported further by the binding that overexpression of nmIκBα, a stable inhibitor of NF-κB, inhibited the induction of IL-6 by bradykinin. Bradykinin activated NF-κB in primary astrocytes as shown by increased DNA binding of NF-κB. These data demonstrate that bradykinin stimulates IL-6 expression through activation of NF-κB, which may explain several inflammatory effects of bradykinin. |
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| Item Description: | Elektronische Reproduktion der Druck-Ausgabe Gesehen am 01.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1471-4159 |
| DOI: | 10.1046/j.1471-4159.1999.0731461.x |