IκBσ, 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

Abstract

The inhibitor of nuclear factor kappa B zeta (IκBσ) is an atypical member of the IêB 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 IκBσ in tumor specimen is associated with poor prognosis. Here we report that IκBσ is upregulated in a glioma cell line resistant towards NFκB-dependent non-apoptotic cell death. Upon γ-irradiation of glioma cells, IκBσ 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 IκBσ reduces the expression of the aforementioned cytokines. We propose a previously unappreciated role of IκBσ in the inflammatory micromilieu as well as progression in glioma.