Improvement of atopic dermatitis in NC/Nga mice by topical application of CpG phosphodiester-ODN.
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-gamma. Furthermore, the expression of IFN-gamma 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.
Laboratory of Dermato-Immunology, Catholic Research Institute of Medical Science, Catholic University of Korea, Seoul, Republic of Korea.
Yang-soon
YS
Kim
Younghwa
Y
Kim
Kang-Jin
KJ
Lee
Hyung-Joo
HJ
Kwon
Doo-Sik
DS
Kim
Tae-Yoon
TY
Kim
D000279:Administration, Cutaneous; D000818:Animals; D018926:Anti-Allergic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics; D004247:DNA / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003876:Dermatitis, Atopic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005452:Fluoresceins / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012869:Skin Absorption
D018926:Anti-Allergic Agents; C408982:CPG-oligonucleotide; C525070:CpG phosphodiester ODN 46-O; C525069:CpG phosphorothioate ODN 1826-S; D016207:Cytokines; D005452:Fluoresceins; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D007073:Immunoglobulin E; D004247:DNA