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In vivo transfection of a cis element ‘decoy’ against signal transducers and activators of the transcription 6 (STAT6) binding site ameliorates the response of contact hypersensitivity

Gene Therapy volume 11, pages 1763–1771 (2004)Cite this article

Abstract

We herein demonstrate that STAT6 plays an important role in the induction of not only acute contact hypersensitivity (CHS), but also chronic CHS in a mouse model using STAT6-deficient (STAT6−/−) mice. We, therefore, determine whether synthetic double-stranded DNA with a high affinity for STAT6 can be introduced in vivo as a decoy cis element to bind the transcriptional factor and block the induction of not only acute CHS but also chronic CHS. Treatment by the transfection of STAT6 decoy oligodeoxynucleotides (ODN), after the induction of 2,4,6-trinitrochlorobenzene or other haptens had a significant inhibitory effect on the induction of both acute CHS and chronic CHS. We thus examined the mechanism of the in vivo effect of the transfection of STAT6 decoy ODN in both acute and chronic CHS. In the histological analysis, the infiltration of eosinophils and degranulated mast cells, and the production of IL-4, IL-6 and eotaxin, but not IFN-γ in the extracts from challenged skin significantly decreased by the transfection of STAT6 decoy ODN. We herein report the first successful in vivo transfer of STAT6 decoy ODN to inhibit acute and chronic CHS, thus providing a new therapeutic strategy not only for the treatment of CHS but also for atopic dermatitis.

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Acknowledgements

We thank Ms Motoko Sekiya for her excellent technical assistance.

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Authors and Affiliations

  1. Department of Environmental Immunodermatology, Postgraduate School, Tokyo Medical & Dental University, Tokyo, Japan

    K Sumi, H Yokozeki, M-H Wu, T Satoh & K Nishioka

  2. Department of Gene Therapy, School of Medicine, Osaka University, Osaka, Japan

    Y Kaneda

  3. Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

    K Takeda & S Akira

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  1. K Sumi
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Sumi, K., Yokozeki, H., Wu, MH. et al. In vivo transfection of a cis element ‘decoy’ against signal transducers and activators of the transcription 6 (STAT6) binding site ameliorates the response of contact hypersensitivity. Gene Ther 11, 1763–1771 (2004). https://doi.org/10.1038/sj.gt.3302345

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