Browsing by Author "Yi, Qiaofang"

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    Phenotyping acute and chronic atopic dermatitis-like lesions in Stat6VT mice identifies a role for IL-33 in disease pathogenesis
    (Springer, 2018-04) DaSilva-Arnold, Sonia C.; Thyagarajan, Anita; Seymour, Leroy J.; Yi, Qiaofang; Bradish, Joshua R.; Al-Hassani, Mohammed; Zhou, Hongming; Perdue, Nikolajs J.; Nemmeth, Val; Krbanjevic, Aleksandar; Serezani, Ana P. M.; Olson, Matthew R.; Spandau, Dan F.; Travers, Jeffrey B.; Kaplan, Mark H.; Turner, Matthew J.; Dermatology, School of Medicine
    The Stat6VT mouse model of atopic dermatitis (AD) is induced by T-cell-specific expression of a constitutively active form of the protein signal transducer and activator of transcription 6 (STAT6). Although AD-like lesions are known to develop in Stat6VT mice, this study was designed to determine if these mice develop acute and chronic phases of disease similar to humans. To address this, AD-like lesions from Stat6VT mice were harvested at two different timepoints relative to their onset. Lesions harvested within 1 week after development were defined as acute lesions, and those present for 1 month or more were defined as chronic lesions. Acute and chronic AD-like lesions from Stat6VT mice exhibited histologic findings and cytokine expression patterns similar to acute and chronic AD lesions in humans. Further analysis revealed increased levels of interleukin (IL)-33 transcripts in AD-like lesions compared to Stat6VT nonlesional and wild-type skin controls. Immunofluorescence also revealed increased numbers of IL-33+ keratinocytes in Stat6VT lesional skin and localized IL-33+ keratinocytes to a keratin 5+ subset. Furthermore, AD-like disease was more severe in IL-33-deficient Stat6VT mice compared to IL-33-sufficient Stat6VT mice. These studies suggest that Stat6VT mice can serve as a model of acute and chronic AD and that IL-33 may attenuate inflammation in this system.
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    The Platelet-activating Factor Receptor Protects Epidermal Cells from Tumor Necrosis Factor (TNF) α and TNF-related Apoptosis-inducing Ligand-induced Apoptosis through an NF-κB-dependent Process
    (American Society for Biochemistry and Molecular Biology, 2001-12-07) Southall, Michael D.; Isenberg, Jason S.; Nakshatri, Harikrishna; Yi, Qiaofang; Pei, Yong; Spandau, Dan F.; Travers, Jeffrey B.
    A number of chemical mediators can induce human keratinocytes and epidermal-derived carcinomas to undergo apoptosis, or programmed cell death. Recent evidence suggests pro-inflammatory cytokines, such as interleukin-1β or transforming growth factor α, protects carcinomas from numerous pro-apoptotic stimuli. Platelet-activating factor (1-alkyl-2-acetyl-3-glycerophosphocholine; PAF) is a lipid mediator with pro-inflammatory effects on numerous cell types. Although PAF can be metabolized to other bioactive lipids, the majority of PAF effects occur through activation of a G protein-coupled receptor. Using a model system created by retroviral transduction of the PAF receptor (PAF-R) into the PAF-R-negative human epidermal cell line KB and the PAF-R-expressing keratinocyte cell line HaCaT, we now demonstrate that activation of the epidermal PAF-R results in protection from apoptosis induced by tumor necrosis factor (TNF) α or TNF-related apoptosis-inducing ligand. The PAF-mediated protection was inhibited by PAF-R antagonists, and protection did not occur in PAF-R-negative KB cells. Additionally, we show protection from TNFα- or TRAIL-induced apoptosis by PAF-R activation is dependent on the transcription factor nuclear factor (NF)-κB, because PAF-R activation-induced NF-κB and epidermal cells transduced with a super-repressor form of inhibitor κB were not protected by the PAF-R. These studies provide a mechanism whereby the epidermal PAF-R, and possibly other G protein-coupled receptors, can exert anti-apoptotic effects through an NF-κB-dependent process.
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    Topical Application of a Vitamin D Analogue Exacerbates Atopic Dermatitis and Induces the Atopic Dermatitis-like Phenotype in Stat6VT mice
    (Wiley, 2013) Turner, Matthew J.; DaSilva-Arnold, Sonia C.; Yi, Qiaofang; Mehrotra, Purvi; Kaplan, Mark H.; Travers, Jeffrey B.; Dermatology, School of Medicine
    Calcipotriene is a topical vitamin D3 analogue approved for the treatment of plaque and scalp psoriasis. We report the case of a 2-year-old boy whose atopic dermatitis (AD) flared in response to application of calcipotriene 0.005% cream and solution for a mistaken diagnosis of plaque and scalp psoriasis. We investigated whether the patient's eruption was secondary to an allergic contact dermatitis. In the Stat6VT mouse model of AD we tested whether calcipotriene could induce the otherwise-spontaneous AD-like phenotype. Closed patch testing was done on the patient with calcipotriene solution and cream, moisturizing cream, and 51% isopropanol. Stat6VT and wild-type (WT) mice were treated for 7 days with calcipotriene solution or vehicle (isopropanol) applied to the right and left upper back skin, respectively, after which mice were followed longitudinally for 10 weeks. Biopsy specimens from prior treatment sites were then collected for histology and RNA isolation. RNA was analyzed for interleukin (IL-4) expression using quantitative polymerase chain reaction. Patch testing was negative. Stat6VT mice, in contrast to WT mice, developed a persistent eczematous dermatitis at sites of calcipotriene application. Clinical and histologic features and high IL-4 transcript levels were consistent with the spontaneous AD-like phenotype seen in Stat6VT mice. At sites of active disease, calcipotriene can worsen a flare of AD. In Stat6VT mice, calcipotriene can induce the AD-like phenotype.