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IFN-alpha induces the human IL-10 gene by recruiting both IFN regulatory factor 1 and Stat3.

Journal of immunology (Baltimore, Md. : 1950) (2003-06-21)
Löms Ziegler-Heitbrock, Mark Lötzerich, Annette Schaefer, Thomas Werner, Marion Frankenberger, Elke Benkhart
ABSTRACT

The anti-inflammatory cytokine IL-10 can be induced by type I IFNs, but the molecular mechanisms involved have remained elusive. With in silico analysis of the human IL-10 promoter we identified a module consisting of an IFN regulatory factor 1 (IRF-1) site and a Stat3 site. We demonstrate that IFN-alpha will induce the binding of IRF-1 and Stat3 to the respective motifs. Mutational analysis revealed that inactivation of the IRF-1 motif substantially reduces trans-activation from 5- to 2-fold and that inactivation of the Stat3 motif completely ablates trans-activation by IFN-alpha. The dominant role of Stat3 in this module was confirmed with the blockade of trans-activation by a dominant negative Stat3. By contrast, Stat1 contributes a minor proportion to the DNA binding to the Stat site, and overexpression will counteract Stat3-mediated trans-activation. The data show that IFN-alpha induces the IL-10 gene via a module consisting of interdependent IRF-1 and Stat3 motifs. Of note, LPS-induced trans-activation does not target this module, since it is independent of the IRF-1 motif but completely depends on Stat3.

MATERIALS
Product Number
Brand
Product Description

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Aprotinin from bovine lung, saline solution, 3-7 TIU/mg protein
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