IκBζ, an atypical member of the inhibitor of nuclear factor kappa B family, is induced by γ-irradiation in glioma cells, regulating cytokine secretion and associated with poor prognosis

Brennenstuhl,Heiko; Armento,Angela; Braczysnki,Anne  Kristin; Mittelbronn,Michel; Naumann,Ulrike

doi:10.3892/ijo.2015.3159

IκBζ, an atypical member of the inhibitor of nuclear factor kappa B family, is induced by γ-irradiation in glioma cells, regulating cytokine secretion and associated with poor prognosis

Authors:
- Heiko Brennenstuhl
- Angela Armento
- Anne Kristin Braczysnki
- Michel Mittelbronn
- Ulrike Naumann
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Affiliations: Hertie Institute for Clinical Brain Research and Center Neurology, Molecular Neurology, Karl Eberhards University of Tübingen, Tübingen, Germany, Edinger Institute (Neurological Institute), Goethe University, Frankfurt am Main, Germany
Published online on: September 14, 2015 https://doi.org/10.3892/ijo.2015.3159
Pages: 1971-1980

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Abstract

The inhibitor of nuclear factor kappa B zeta (IκBζ) is an atypical member of the IκB protein family. Its function in regulating the activity of the transcription factor nuclear factor kappa B (NFκB) as well as its involvement in cancer-associated processes is poorly understood. In glioma patients, enhanced expression of IκBζ in tumor specimen is associated with poor prognosis. Here we report that IκBζ is upregulated in a glioma cell line resistant towards NFκB-dependent non-apoptotic cell death. Upon γ-irradiation of glioma cells, IκBζ expression is enhanced, and subsequently serves as a transcriptional activator of the tumor promoting cytokines interleukin (IL-6), IL-8 and chemokine (C-X-C motif) ligand 1 (CXCL1) that are known to be involved in glioma associated inflammatory processes. In contrast, shRNA-mediated knockdown of IκBζ reduces the expression of the aforementioned cytokines. We propose a previously unappreciated role of IκBζ in the inflammatory micromilieu as well as progression in glioma.

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