Improvement of Atopic Dermatitis in NC/Nga Mice by Topical Application of CpG Phosphodiester-ODN

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease with pruritic and eczematous lesions characterized by increased total IgE level, inflammatory cell infiltration, and the elevated expression of Th2 cytokines. Synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides are known to have immunostimulatory activities in mice and to convert from Th2 to Th1 immune responses in AD. Previous work has shown clinical effectiveness of CpG phosphorothioate-ODN in AD mice model. However, due to longer in vivo half-life and the possibility of causing unwanted side effects, therapeutic use of CpG phosphorothioate-ODN can be limited. Thus, we investigated the efficacy of CpG phosphodiester-ODN with a novel sequence in NC/Nga mice. Topical application of phosphodiester-ODN penetrated rapidly from epidermis to the lymph nodes, accompanied by reduced infiltration of inflammatory cells and decreased number of cells expressing cytokines such as IL-4, IL-10 and IFN-γ. Furthermore, the expression of IFN-γ was reduced in the CpG ODNs-treated NC/Nga mice while the expression of IL-12p40 was increased, suggesting stimulation of Th1 immune response. The expression of IL-10 was strongly reduced, which meant the suppression of Th2 immune response in NC/Nga mice, accompanied by reduced level of IgE and IgG1, but increased level of IgG2a in sera. Since phosphodiester-ODN has been shown to cause minimum side effect comparing its phosphorothioate counterpart, it is proposed to become a new therapeutic modality for AD.

Effects of topical application ofAstragalus membranaceuson allergic dermatitis

“…The serum level is an indicator of improved AD symptoms. (12) In the present study, the IgE level tended to decrease in the AM-treated group.…”

“…After 3 days of treatment, the mice were not treated for 5 days (day 3-7). Then, the treatment was repeated with 0.5% DNCB (days [8][9][10][11][12][13][14][15][16]. After the SDS and DNCB treatments, AM group was treated with 1% AM in phosphate-buffered saline (PBS), whereas vehicle and DNCB groups were treated with PBS.…”

Pep-1 peptide-conjugated elastic liposomal formulation of taxifolin glycoside for the treatment of atopic dermatitis in NC/Nga mice

“…Serum levels of IL-4, IgE and IFN-␥ in treated mice were quantified using a previously described method (Kim et al, 2007). All the blood specimens were collected from the retro-orbital plexus while the mice were sedated under ether anesthesia.…”

Tat peptide-admixed elastic liposomal formulation of hirsutenone for the treatment of atopic dermatitis in Nc/Nga mice

“…32 Blood was collected from the retroorbital plexus of mice under ether anesthesia. Serum was obtained by centrifugation of whole blood at 12,000 rpm and was stored at −20°C until use.…”