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SOCS-1 and SOCS-3 inhibit IL-4 and IL-13 induced activation of Eotaxin-3/CCL26 gene expression in HEK293 cells
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Hebenstreit, Daniel, Luft, P., Schmiedlechner, A., Duschl, A. and Horejshoeck, J. (2005) SOCS-1 and SOCS-3 inhibit IL-4 and IL-13 induced activation of Eotaxin-3/CCL26 gene expression in HEK293 cells. Molecular Immunology, Volume 42 (Number 3). pp. 295-303. doi:10.1016/j.molimm.2004.09.004 ISSN 0161-5890.
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Official URL: http://dx.doi.org/10.1016/j.molimm.2004.09.004
Abstract
Secretion of various chemokines including Eotaxin-3/CCL26 results in the attraction of eosinophils to sites of allergic inflammation. IL-4/IL-13-induced activation of the Eotaxin-3/CCL26 gene in human dermal fibroblasts was shown to be a STAT6-dependent process mediated by a single STAT6 binding motif located upstream of the transcription initiation site. The suppressors of cytokine signaling 1–3 (SOCS 1–3) are members of a recently discovered family of proteins acting as negative regulators of cytokine signaling. We show here, that transfection of SOCS-1 and SOCS-3 but not SOCS-2 expression vectors inhibited IL-4/IL-13 induced secretion of Eotaxin-3/CCL26. Further, using Eotaxin-3/CCL26 promoter reporter gene constructs, we could show that, upon cotransfection of SOCS-1 and SOCS-3 expression vectors, IL-4 and IL-13 induced luciferase activity was strongly reduced. This effect was not seen when SOCS-2 was cotransfected. Further, EMSA studies with nuclear extracts prepared from IL-4/IL-13 induced HEK293 cells were conducted. The nuclear extracts of cells transfected with SOCS-1 or SOCS-3 did not form complexes with oligonucleotide probes corresponding to the STAT6 binding site in the Eotaxin-3/CCL26 promoter. In contrast, complex formation upon SOCS-2-transfection was comparable to mock-transfected cells. Further, the levels of phosphorylated STAT6 in IL-4 and IL-13 treated cells were markedly reduced when the cells had been transfected with SOCS-1 or SOCS-3, confirming the role of these negative regulators for the IL-4 and IL-13 induced activation of Eotaxin-3/CCL26 gene expression. The insertion of amino acid exchanges into the kinase inhibitory regions of SOCS-1 and SOCS-3 demonstrated a requirement of these domains for a proper inhibitory function.
Item Type: | Journal Article | ||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Journal or Publication Title: | Molecular Immunology | ||||||||
Publisher: | Elsevier | ||||||||
ISSN: | 0161-5890 | ||||||||
Official Date: | February 2005 | ||||||||
Dates: |
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Volume: | Volume 42 | ||||||||
Number: | Number 3 | ||||||||
Page Range: | pp. 295-303 | ||||||||
DOI: | 10.1016/j.molimm.2004.09.004 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access |
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