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      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.

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

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          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.

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