title: GATA-3 regulates contact hyperresponsiveness in a murine model of allergic dermatitis.
abstract: Contact hypersensitivity (CHS) is thought to be associated mainly with the activation of T helper (Th) type 1 cells. However, evidence also suggests that Th type 2 cells (Th2) and cytokines play roles in the development of CHS in humans. The present study examines the Th2 response during the development of CHS in response to 2,4,6-trinitrochlorobenzene (TNCB) in GATA-3-transgenic (GATA-3 Tg) mice. GATA-3 Tg mice were immunized with 7% TNCB applied to abdominal shaved skin. Seven days later, the mice were challenged with 1% TNCB applied to the left ear. Ear swelling, cytokine production in the skin of the ear, and the levels of IgE, IgG1 and IgG2a were measured. Furthermore, we examined the effects of medical treatment on TNCB-induced contact dermatitis using this model. The ear-swelling responses of TNCB-sensitized/challenged GATA-3 Tg mice were significantly greater than those of similarly treated wild-type (WT) mice. The expression of both IL-5 and IL-13 in TNCB sensitized/challenged skin tissues and the IgE response after challenge were obviously increased in the GATA-3 Tg mice, whereas the expression of IFN-γ was identical in the challenged skin tissues of GATA-3-Tg and WT mice. When TNCB-sensitized GATA-3 Tg mice were treated with a high dose of tacrolimus, ear swelling was not significantly decreased, compared with the results in WT mice. These results suggest that GATA-3-induced Th2-dominant responses play a critical role in the pathogenesis of allergic types of dermatitis, such as atopic dermatitis, and may lead to useful new drug development in the future.
authors: Departments of Microbiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan. hidetama@med.kitasato-u.ac.jp
authors: Hidekazu
authors: H
authors: Tamauchi
authors: Yasuyuki
authors: Y
authors: Amoh
authors: Mamoru
authors: M
authors: Itoh
authors: Masazumi
authors: M
authors: Terashima
authors: Mikio
authors: M
authors: Masuzawa
authors: Sonoko
authors: S
authors: Habu
authors: Kensei
authors: K
authors: Katsuoka
authors: Kazuya
authors: K
authors: Iwabuchi
mesh_terms: D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010853:Picryl Chloride / Q000008:administration & dosage; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects; D018418:Th2 Cells / Q000276:immunology / Q000637:transplantation
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018793:Interleukin-13; D015848:Interleukin-5; D007073:Immunoglobulin E; D016559:Tacrolimus; D010853:Picryl Chloride