Involvement of nuclear factor-kappa B in bcl-xL-induced interleukin 8 expression in glioblastoma

Chiara Gabellini, Laura Castellini, Daniela Trisciuoglio, Michael Kracht, Gabriella Zupi, Donatella Del Bufalo

Research output: Contribution to journalArticlepeer-review


We recently reported that bcl-xL regulates interleukin 8 (CXCL8) protein expression and promoter activity in glioblastoma cells. In this paper we demonstrate that CXCL8 induction by bcl-xL is mediated through a nuclear factor-kappa B (NF-kB)-dependent mechanism. Mutational studies on the CXCL8 promoter showed that NF-kB binding site was required for bcl-xL-induced promoter activity and an enhanced nuclear expression of NF-kB subunits p65 and p50 was observed after bcl-xL over-expression. Electrophoretic mobility shift assay showed an increased DNA-binding activity of NF-kB in bcl-xL over-expressing cells and the use of specific antibodies confirmed the involvement of p65 and p50 in NF-kB activity on CXCL8 promoter sequence. NF-kB activity regulation by bcl-xL involved IkBα and IKK complex signaling pathway. In fact, bcl-xL over-expression induced a decrease of cytoplasmic expression of the IkBα protein, paralleled by an increase in the phosphorylation of the same IkBα and IKKα/β. Moreover, the down-regulation of the ectopic or endogenous bcl-xL expression through RNA interference confirmed the ability of bcl-xL to modulate NF-kB pathway, and the transient expression of a degradation-resistant form of the cytoplasmic NF-kB inhibitor IkBα in bcl-xL transfectants confirmed the involvement of that inhibitor in bcl-xL-induced CXCL8 expression and promoter activity. In conclusion, our results demonstrate the role of NF-kB as the mediator of bcl-xL-induced CXCL8 up-regulation in glioblastoma cells.

Original languageEnglish
Pages (from-to)871-882
Number of pages12
JournalJournal of Neurochemistry
Issue number3
Publication statusPublished - Nov 2008


  • Bcl-xL
  • Glioblastoma
  • Interleukin 8
  • Nuclear factor-kappa B

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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