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

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.