Signal transducer and activator of transcription STAT3 plays a major role in gp130-mediated acute phase protein gene activation

Acta Biochim Pol. 2003;50(3):595-601.

Abstract

Interleukin-6 is a potent inducer of acute-phase response gene transcription. The intracellular signal transduction mechanisms by which this and other biological effects of the cytokine are achieved include activation of the JAK-STAT signaling pathway. More specifically, activation of the signal transducers and activators of transcription STAT1, 3, and 5 in response to IL-6 has been described. We examined the relative potency of these three STAT factors for the activation of acute-phase gene promoters in HepG2 cells in a reporter gene-based assay, where specific STAT factors could be activated via recombinant receptor constructs bearing different STAT-recruiting modules. These experiments indicate that amongst the STAT factors known to be activated by IL-6 STAT3 is the most potent activator of acute-phase gene transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism*
  • Antigens, CD / metabolism*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cloning, Molecular
  • Cytokine Receptor gp130
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / physiology
  • Genes, Reporter / genetics
  • Humans
  • Interleukin-6 / metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Milk Proteins*
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • Signal Transduction / physiology
  • Trans-Activators / metabolism*
  • Transcription, Genetic / genetics
  • Transcriptional Activation
  • Tumor Cells, Cultured

Substances

  • Acute-Phase Proteins
  • Antigens, CD
  • DNA-Binding Proteins
  • IL6ST protein, human
  • Interleukin-6
  • Membrane Glycoproteins
  • Milk Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • STAT5 Transcription Factor
  • Trans-Activators
  • Cytokine Receptor gp130