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IL-4 and IL-13 induce SOCS-1 gene expression in A549 cells by three functional STAT6-binding motifs located upstream of the transcription initiation site
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Hebenstreit, Daniel, Luft, P., Schmiedlechner, A., Regl, G., Frischauf, A.-M., Aberger, F., Duschl, A. and Horejs-Hoeck, J. (2003) IL-4 and IL-13 induce SOCS-1 gene expression in A549 cells by three functional STAT6-binding motifs located upstream of the transcription initiation site. The Journal of Immunology, Volume 171 (Number 11). pp. 5901-5907. doi:10.4049/jimmunol.171.11.5901 ISSN 0022-1767.
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Official URL: http://dx.doi.org/10.4049/jimmunol.171.11.5901
Abstract
Proteins of the suppressors of cytokine signaling (SOCS) family have important functions as negative regulators of cytokine signaling. We show here that SOCS-1 expression can be induced in the human epithelial lung cell line A549 by IL-4 and IL-13. Analysis of reporter gene constructs under control of the SOCS-1 promoter provides evidence that IL-4- and IL-13-induced up-regulation is dependent on three IFN-γ-activated sequence motifs of the sequence TTC(N)4GAA, which is known for binding STAT6. The three motifs are situated close to each other ∼600 bp upstream of the transcriptional initiation site. When mutations were inserted into all three IFN-γ-activated sequence motifs at the same time, IL-4-IL-13-induced luciferase activity was abrogated. With single and double mutants, promoter activity was diminished in comparison with the wild-type promoter. STAT6 is therefore required for IL-4-IL-13-dependent SOCS-1 expression in A549 cells, and the three identified binding motifs cooperate to induce maximal transcription. EMSAs conducted with nuclear extracts of IL-4- and IL-13-stimulated A549 cells showed that STAT6 was able to bind to each of the three binding motifs. Finally, cotransfection of a SOCS-1 expression vector inhibited activation of SOCS-1 promoter luciferase constructs. Thus, SOCS-1 is able to autoregulate its expression via a negative feedback loop.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Journal or Publication Title: | The Journal of Immunology | ||||
Publisher: | American Association of Immunologists | ||||
ISSN: | 0022-1767 | ||||
Official Date: | 1 December 2003 | ||||
Dates: |
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Volume: | Volume 171 | ||||
Number: | Number 11 | ||||
Page Range: | pp. 5901-5907 | ||||
DOI: | 10.4049/jimmunol.171.11.5901 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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