Interleukin-1 beta uses common and distinct signaling pathways for induction of the interleukin-6 and tumor necrosis factor alpha genes in the human astrocytoma cell line U373

J Neurochem. 1996 Apr;66(4):1496-503. doi: 10.1046/j.1471-4159.1996.66041496.x.

Abstract

Cytokines are involved in the etiology of different disorders of the CNS. For a better understanding of their pathogenic role, we analyzed signal transduction pathways mediating the interleukin (IL)-1 beta-induced synthesis of IL-6 and tumor necrosis factor alpha (TNF alpha) in the human astrocytoma cell line U373 MG. Both protein kinase C and reactive oxygen intermediates (ROIs) were involved in IL-6 and TNF alpha gene expression by IL-1 beta. In contrast, protein tyrosine kinases were only necessary for expression of the IL-6 gene. Whereas activation of protein kinase A was able to induce expression of the IL-6 gene, it did not induce TNF alpha gene expression and was not involved in IL-1 beta-induced IL-6 and TNF alpha gene expression. Activation of the transcription factor nuclear factor-kappa B by IL-1 beta involved ROIs, whereas the IL-1 beta-induced activation of the transcription factor AP-1 was mediated via protein kinase C. Our findings provide the basis for the development of specific drugs for the treatment of disorders of the CNS in which cytokines play a pathogenic role.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytoma / enzymology
  • Astrocytoma / genetics*
  • Cyclic AMP-Dependent Protein Kinases / immunology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Gene Expression Regulation
  • Gene Expression Regulation, Enzymologic* / immunology
  • Humans
  • Immunohistochemistry
  • Interleukin-1 / pharmacology*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Protein Kinase C / immunology
  • Protein Kinase C / metabolism
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology*
  • Transcription Factor AP-1 / immunology
  • Transcription Factor AP-1 / metabolism
  • Transcription Factors / immunology
  • Tumor Cells, Cultured / enzymology
  • Tumor Cells, Cultured / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Interleukin-1
  • Interleukin-6
  • NF-kappa B
  • RNA, Messenger
  • Reactive Oxygen Species
  • Transcription Factor AP-1
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Protein-Tyrosine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C