title: The atopic dermatitis-like symptoms induced by MC903 were alleviated in JNK1 knockout mice.
abstract: Atopic dermatitis (AD) is a common allergic disease, imposing large social and economic burdens worldwide. Atopic dermatitis is characterized by eczematous skin lesions and immunoglobulin E (IgE) hypersecretion. We investigated the role of JNK1 on the development of AD in mice. The vitamin D3 analogue MC903, a psoriasis therapeutic drug, was used to induce AD-like symptoms in wild-type (WT) and JNK1-/- mice. The symptoms of AD were less severe in JNK1-/- mice compared with WT mice. JNK1-/- mice showed less ear thickening and infiltration of eosinophils and mast cells in AD-like lesions than did WT mice when treated with MC903. MC903-treated JNK1-/- mice also showed significantly lower level of serum IgE, which was elevated in MC903-treated WT mice. Splenocytes isolated from MC903-treated WT and JNK1-/- mice were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies. Splenocytes from JNK1-/- mice produced lower levels of T-helper (Th2) cytokines (interleukin-4 and -13) and transcription factor GATA-binding protein 3, and produced increased levels of the Th1 cytokines interferon-γ and transcription factor T-box expressed in T cells. Our results indicate that JNK1 plays an important role in the pathogenesis of AD and may be a useful target for therapies to ameliorate AD.
authors.affiliation: * WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea;
authors.forename: Jinhwan
authors.initials: J
authors.lastname: Choi
authors.forename: Jong Rhan
authors.initials: JR
authors.lastname: Kim
authors.forename: Heejeung
authors.initials: H
authors.lastname: Kim
authors.forename: Yoon A
authors.initials: YA
authors.lastname: Kim
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
chemical_list: D016207:Cytokines; C055085:calcipotriene; D007073:Immunoglobulin E; D048055:Mitogen-Activated Protein Kinase 8; D002117:Calcitriol
keywords: GATA-3; IgE; JNK1; T-bet.; atopic dermatitis; cytokines