title: Differential expression of inflammation-related genes in IL-4 transgenic mice before and after the onset of atopic dermatitis skin lesions.
abstract: IL-4 plays an important role in the pathogenesis of atopic dermatitis (AD), a common chronic inflammatory skin disease. We have generated IL-4 transgenic (Tg) mice by over-expressing IL-4 in the epidermis. These mice spontaneously develop chronic pruritic inflammatory skin lesions, which meet the clinical and histological diagnostic criteria for human AD. Systemic survey of immune-related genes in this mouse model, however, has not been performed. In this study, we utilize PCR array technique to examine hundreds of inflammation-related genes in the IL-4 Tg mice before and after the onset of skin lesions as well as in their wild type (WT) littermates. Only those genes with at least 2-fold up-regulation or down-regulation and with a P-value of less than 0.05 in comparison to WT controls were identified and analyzed. In the skin lesions, many chemokines, pro-inflammatory cytokines, and other AD-related factors are dysregulated compared to the wild type mice. Particularly, CXCL5, IL-1β, IL-24, IL-6, oncostatin M, PTGS2, FPR1 and REG3γ are up-regulated several hundred-fold. In the pre-lesional group that shows no obvious skin abnormality on clinical observation, 30 dysregulated genes are nevertheless identified though the fold changes are much less than that of the lesional group, including CCL6, CCL8, CCL11, CCL17, CXCL13, CXCL14, CXCR3 and IL-12Rβ2. Finally using ELISA, we demonstrate that 4 most dramatically up-regulated factors in the skin are also elevated in the peripheral blood of the IL-4 Tg mice. Taken together, our data have identified hundreds of dysregulated factors in the IL-4 Tg mice before and after the onset of skin lesions. Future detailed examination of these factors will shed light on our understanding of the development and progression of AD and help to discover important biomarkers for clinical AD diagnosis and treatment.
authors.affiliation: Department of Dermatology, University of Illinois, Chicago, IL, USA. Electronic address: lbao1@uic.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.affiliation: Department of Dermatology, University of Illinois, Chicago, IL, USA.
authors.forename: Huayi
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, University of Illinois, Chicago, IL, USA.
authors.forename: Girish C
authors.initials: GC
authors.lastname: Mohan
authors.affiliation: Department of Dermatology, University of Illinois, Chicago, IL, USA.
authors.forename: Kui
authors.initials: K
authors.lastname: Shen
authors.affiliation: Department of Dermatology, University of Illinois, Chicago, IL, USA; Department of Microbiology/Immunology, University of Illinois, Chicago, IL, USA; Medical Service, Jesse Brown VA Med Center, Chicago, IL, USA. Electronic address: larrycha@uic.edu.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Chan
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics*; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D015847:Interleukin-4
keywords: Atopic dermatitis; IL-4 transgenic mice; PCR array