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