Enhanced phenotype of calcipotriol‐induced atopic dermatitis in filaggrin‐deficient mice
| Autor: | Yaxing Bai, Bingyu Pang, Erle Dang, Chen Zhang, Jixin Gao, Hongjiang Qiao, Zhongbin Sun, Gang Wang, Chunying Xiao, Meng Fu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Thymic stromal lymphopoietin medicine.medical_treatment Inflammation Filaggrin Proteins Biochemistry Dermatitis Atopic Pathogenesis Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Calcitriol Intermediate Filament Proteins Genetics medicine Animals Molecular Biology Calcipotriol Mice Knockout business.industry Interleukin Atopic dermatitis medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Cytokine chemistry Immunology Female Dermatologic Agents medicine.symptom business 030217 neurology & neurosurgery Biotechnology Filaggrin |
| Zdroj: | The FASEB Journal. 35 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | Impaired function of filaggrin (FLG) is a major predisposing factor for atopic dermatitis (AD). Several studies on FLG-deficient (Flg-/- ) mice have indicated an essential role for FLG in the skin barrier and the development of AD, but none of the studies have described the characteristics on Flg-/- mice with calcipotriol (CPT)-induced atopic dermatitis, which restricts the comprehensive understanding of functions of FLG. The present study sought to generate Flg-/- mice and applied CPT to produce AD-like dermatitis for in vivo analysis of the FLG functions. CPT was applied on the skin of Flg-/- mice to establish the AD-like dermatitis mouse model. The lesion inflammation was evaluated by gross ear thickness, histopathology, immunofluorescence, and cytokine production. Also, mucopolysaccharide polysulfate (MPS) and ceramide were used to observe the therapeutic function in this model. The results showed that the inflammation of CPT-induced dermatitis in Flg-/- mice was more severer than that of wild-type (WT) mice, as evident by the increased level of gross appearance, ear thickness, inflammatory cell infiltration (mast cells and CD3+ T cells), and inflammatory cytokine expression (interleukin (IL)-4, IL-6, IL-13, and thymic stromal lymphopoietin (TSLP)). The emollients MPS and ceramide partially restored the epidermal function and alleviated the skin inflammation in Flg-/- mice with CPT-induced AD-like dermatitis. The current study demonstrated that skin barrier protein FLG is critical in the pathogenesis of AD. Also, the AD mouse model induced by CPT in Flg-/- mice could be utilized to search for drug targets in AD. |
| Databáze: | OpenAIRE |
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