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Regulation of immunological balance by sustained interferon-γ gene transfer for acute phase of atopic dermatitis in mice.
Gene Ther. 2013 May; 20(5):538-44.GT

Abstract

Interferon (IFN)-γ, a potent T helper 1 (Th1) cell cytokine, is suggested to suppress Th2 cell responses. Here, we aimed to investigate whether pCpG-Muγ, a plasmid continuously expressing murine IFN-γ, is an effective treatment of atopic dermatitis, a Th2-dominant skin disease. Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) atopic mice with early dermatitis were transfected with pCpG-Muγ by a hydrodynamic tail vein injection at a dose of 0.05 or 0.2 pmol per mouse. The skin lesions improved only in mice receiving the high dose of pCpG-Muγ. IFN-γ gene transfer resulted in a high mRNA expression of IFN-γ and interleukin (IL)-12 and regulatory T cell (Treg) related cytokines, such as IL-10 and transforming growth factor-β, in the spleen, whereas it reduced the IL-4 mRNA expression, and serum levels of immunoglobulin (Ig) G1 and IgE. In addition, the gene transfer markedly inhibited the epidermal thickening, infiltration of inflammatory cells into the skin, the occurrence of dry skin and pruritus. No exacerbating effect on the Th1-mediated contact dermatitis was observed after IFN-γ gene transfer. Taken together, these results indicate that sustained IFN-γ gene transfer induced polarized Th1 immunity under Th2-dominant conditions in NC/Nga mice, leading to an improvement in the symptoms of acute atopic dermatitis without adverse side effects.

Authors+Show Affiliations

Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22914497

Citation

Watcharanurak, K, et al. "Regulation of Immunological Balance By Sustained Interferon-γ Gene Transfer for Acute Phase of Atopic Dermatitis in Mice." Gene Therapy, vol. 20, no. 5, 2013, pp. 538-44.
Watcharanurak K, Nishikawa M, Takahashi Y, et al. Regulation of immunological balance by sustained interferon-γ gene transfer for acute phase of atopic dermatitis in mice. Gene Ther. 2013;20(5):538-44.
Watcharanurak, K., Nishikawa, M., Takahashi, Y., Kabashima, K., Takahashi, R., & Takakura, Y. (2013). Regulation of immunological balance by sustained interferon-γ gene transfer for acute phase of atopic dermatitis in mice. Gene Therapy, 20(5), 538-44. https://doi.org/10.1038/gt.2012.69
Watcharanurak K, et al. Regulation of Immunological Balance By Sustained Interferon-γ Gene Transfer for Acute Phase of Atopic Dermatitis in Mice. Gene Ther. 2013;20(5):538-44. PubMed PMID: 22914497.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of immunological balance by sustained interferon-γ gene transfer for acute phase of atopic dermatitis in mice. AU - Watcharanurak,K, AU - Nishikawa,M, AU - Takahashi,Y, AU - Kabashima,K, AU - Takahashi,R, AU - Takakura,Y, Y1 - 2012/08/23/ PY - 2012/8/24/entrez PY - 2012/8/24/pubmed PY - 2013/11/2/medline SP - 538 EP - 44 JF - Gene therapy JO - Gene Ther VL - 20 IS - 5 N2 - Interferon (IFN)-γ, a potent T helper 1 (Th1) cell cytokine, is suggested to suppress Th2 cell responses. Here, we aimed to investigate whether pCpG-Muγ, a plasmid continuously expressing murine IFN-γ, is an effective treatment of atopic dermatitis, a Th2-dominant skin disease. Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) atopic mice with early dermatitis were transfected with pCpG-Muγ by a hydrodynamic tail vein injection at a dose of 0.05 or 0.2 pmol per mouse. The skin lesions improved only in mice receiving the high dose of pCpG-Muγ. IFN-γ gene transfer resulted in a high mRNA expression of IFN-γ and interleukin (IL)-12 and regulatory T cell (Treg) related cytokines, such as IL-10 and transforming growth factor-β, in the spleen, whereas it reduced the IL-4 mRNA expression, and serum levels of immunoglobulin (Ig) G1 and IgE. In addition, the gene transfer markedly inhibited the epidermal thickening, infiltration of inflammatory cells into the skin, the occurrence of dry skin and pruritus. No exacerbating effect on the Th1-mediated contact dermatitis was observed after IFN-γ gene transfer. Taken together, these results indicate that sustained IFN-γ gene transfer induced polarized Th1 immunity under Th2-dominant conditions in NC/Nga mice, leading to an improvement in the symptoms of acute atopic dermatitis without adverse side effects. SN - 1476-5462 UR - https://www.unboundmedicine.com/medline/citation/22914497/Regulation_of_immunological_balance_by_sustained_interferon_γ_gene_transfer_for_acute_phase_of_atopic_dermatitis_in_mice_ L2 - https://doi.org/10.1038/gt.2012.69 DB - PRIME DP - Unbound Medicine ER -