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Functional characterization of IL-13 receptor α2 gene promoter: a critical role of the transcription factor STAT6 for regulated expression

Oncogene volume 22, pages 3386–3394 (2003)Cite this article

Abstract

Interleukin (IL)-4 and IL-13 are two structurally and functionally related cytokines that have overlapping but also distinct biological activities. One of the components of the IL-13 receptor, the α2 chain (IL-13Rα2), has been reported to downregulate the cell responsiveness to IL-13, without affecting IL-4 signaling. Here, we report that TNFα synergizes with either IL-4 or IL-13 in inducing the IL-13Rα2 chain at both the mRNA and protein levels in the HaCaT human keratinocyte cell line. Further studies by 5′RACE identified as yet undescribed exonic sequences of the IL-13Rα2 5′UTR, provided evidence for the expression of alternatively spliced IL-13Rα2 transcripts and defined the transcription start of the IL-13Rα2 gene. A 1.5 kb region upstream of the first exon of the IL-13Rα2 gene displayed basal promoter activity when inserted in a reporter plasmid and transiently transfected in HaCaT cells. This promoter activity was further increased in response to IL-4 and IL-13. Furthermore, by electrophoretic mobility shift assay and site-directed mutagenesis, we showed that the IL-4/IL-13-induced promoter activity depended upon a positively acting STAT6 response element. Finally, TNFα was shown to potentiate IL-4/IL-13-induced IL-13Rα2 promoter activity when the same reporter construct was studied in stably but not in transiently transfected cells. These results suggest that the synergistic effect of TNFα on IL-4/IL-13-induced IL-13Rα2 expression is dependent upon chromatin re-modeling events.

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Acknowledgements

We are grateful to Dr P Ferrara for providing IL-4 and IL-13. This work was supported in part by a fellowship to MD D and grants from Association pour la Recherche sur le Cancer (Grant # 5963).

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  1. INSERM U461, Faculte de Pharmacie, 5, rue JB Clement, Chatenay Malabry Cedex, 92296, France

    Muriel D David, Jacques Bertoglio & Josiane Pierre

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Correspondence to Josiane Pierre.

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David, M., Bertoglio, J. & Pierre, J. Functional characterization of IL-13 receptor α2 gene promoter: a critical role of the transcription factor STAT6 for regulated expression. Oncogene 22, 3386–3394 (2003). https://doi.org/10.1038/sj.onc.1206352

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