Bradykinin induces interleukin-6 expression in astrocytes through activation of nuclear factor-κB

Markus Schwaninger*, Svea Sallmann, Nicole Petersen, Armin Schneider, Simone Prinz, Towia A. Libermann, Matthias Spranger

*Corresponding author for this work
79 Citations (Scopus)


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 bisindolylmaleimide 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 an 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 finding that overexpression of nmlκBα, 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.

Original languageEnglish
JournalJournal of Neurochemistry
Issue number4
Pages (from-to)1461-1466
Number of pages6
Publication statusPublished - 28.09.1999

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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