Redox regulation of lipopolysaccharide (LPS)-induced interleukin-8 (IL-8) gene expression mediated by NF kappa B and AP-1 in human astrocytoma U373 cells

Biochem Biophys Res Commun. 1997 Mar 17;232(2):568-73. doi: 10.1006/bbrc.1997.6264.

Abstract

LPS-induced expression of the IL-8 gene was markedly enhanced by H2O2 or by deprivation of the cellular antioxidant glutathione by L-buthionine-(S,R)-sulfoximine (BSO) in human astrocytoma U373 cells. In contrast, it was markedly suppressed by the reductant N-acetyl-L-cysteine (NAC) and other antioxidants. Transient expression analysis using the chloramphenicol acetyltransferase assay revealed that activation of the IL-8 promoter by LPS was stimulated by BSO and was suppressed by NAC; likewise LPS-induced activation of both NF kappa B and AP-1 was enhanced by BSO and inhibited by NAC. These results suggest that LPS-induced IL-8 gene expression is regulated by cellular redox via modulation of these transcription factors.

MeSH terms

  • Acetylcysteine / pharmacology
  • Antioxidants / pharmacology
  • Astrocytoma / genetics*
  • Astrocytoma / metabolism
  • Buthionine Sulfoximine / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics*
  • Lipopolysaccharides / pharmacology*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / pharmacology*
  • Oxidation-Reduction
  • Transcription Factor AP-1 / antagonists & inhibitors
  • Transcription Factor AP-1 / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antioxidants
  • Interleukin-8
  • Lipopolysaccharides
  • NF-kappa B
  • Transcription Factor AP-1
  • Buthionine Sulfoximine
  • Acetylcysteine