title: GATA binding protein 3 overexpression and suppression significantly contribute to the regulation of allergic skin inflammation.
abstract: GATA binding protein 3 (GATA3) is a key molecule regulating the balance in the ratio of type 1 helper T (Th1) cells to type 2 helper T (Th2) cells, which is thought to be indicative of the pathogenesis of allergic diseases such as asthma and atopic dermatitis. The aim of this study was to investigate the role of GATA3 in allergic skin inflammation. Transgenic (Tg) mice overexpressing human GATA3 (hGATA3) were produced by the microinjection of pCMV/hGATA3 constructs into fertilized mouse eggs. The hGATA3 gene was successfully expressed at the protein level in the lymph node and thymus of CMV/hGATA3 transfected cells and Tg mice. CMV/hGATA3 Tg mice showed a significant increase in the allergic skin inflammation response such as ear thickness, draining auricular lymph node (aLN) weight, epidermal thickness, inflammatory cell number and Th2 immunoglobulin (Ig) concentration compared to wild-type (WT) mice after phthalic anhydride (PA) treatment. Furthermore, the secretion of Th2 type cytokines was increased by PA treatment in CMV/hGATA3 Tg mice, while the secretion of Th1 type cytokine was suppressed under the same conditions. However, the increased levels of Th2 type cytokines in CMV/hGATA3 Tg mice were almost recovered by the down-regulation of GATA3 expression with D-pinitol treatment. Therefore, these findings suggest that GATA3 could be considered as a potential target regulating the mechanism responsible for the differences in allergic skin inflammation.
authors.affiliation: Department of Laboratory Animal Resources, National Institute of Food and Drug Evaluation, Korea FDA, Cheongwon 363-951, Republic of Korea.
authors.forename: Chang Jun
authors.initials: CJ
authors.lastname: Bae
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Sun Bo
authors.initials: SB
authors.lastname: Shim
authors.forename: Seung Wan
authors.initials: SW
authors.lastname: Jee
authors.forename: Su Hae
authors.initials: SH
authors.lastname: Lee
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Woo
authors.forename: Chang Kyu
authors.initials: CK
authors.lastname: Lee
authors.forename: Dae Youn
authors.initials: DY
authors.lastname: Hwang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004423:Ear / Q000473:pathology; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D019169:Jurkat Cells; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D012867:Skin / Q000276:immunology* / Q000503:physiopathology; D013950:Thymus Gland / Q000276:immunology
chemical_list: D016207:Cytokines; D050990:GATA3 Transcription Factor; D007074:Immunoglobulin G