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

100%

May P., Schniertshauer U., Gerhartz C., Horn F., Heinrich P. C.

2003

vol. 50

issue 3

595-601

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.

Interleukin-6 biology is coordinated by membrane bound and soluble receptors.

75%

Rose-John S.

2003

vol. 50

issue 3

603-611

Cytokine receptors exist in membrane bound and soluble form. Both forms bind their ligands with comparable affinity. While most soluble receptors are antagonists in that they compete for the ligands with their membrane counterparts, some soluble receptors are agonists. In this case, the complex of ligand and soluble receptor binds on target cells to a second receptor subunit and initiates signal transduction. Soluble receptors of the IL-6 family of cytokines are agonists. In vivo, the IL-6/soluble IL-6R complex stimulates several types of target cells not stimulated by IL-6 alone, since they do not express the membrane bound IL-6R. This process has been named transsignaling. We have shown that in several chronic inflammatory diseases like chronic inflammatory bowl disease, peritonitis and rheumatoid arthritis, transsignaling via the soluble IL-6R complexed to IL-6 is a crucial point in the transition from the acute to the chronic state of the disease. The mechanism by which the IL-6/ soluble IL-6R complex regulates the inflammatory state is discussed.

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2 Acta Biochimica Polonica

2 2003

1 Gerhartz C.

1 Heinrich P. C.

1 Horn F.

1 May P.

1 Rose-John S.

1 Schniertshauer U.

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

Interleukin-6 biology is coordinated by membrane bound and soluble receptors.