1. Role of the complement anaphylatoxin C5a-receptor pathway in atopic dermatitis in mice
- Author
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Lin Dang, Yan Wang, Jikui Xiong, Lei He, Yuzhen Li, and Bingxue Bai
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Gene Expression ,Complement C5a ,Immunoglobulin E ,Biochemistry ,Dermatitis, Atopic ,Pathogenesis ,chemistry.chemical_compound ,Interferon-gamma ,Mice ,Skin fold ,Internal medicine ,interferon-γ ,Genetics ,medicine ,Dinitrochlorobenzene ,Animals ,Interferon gamma ,Molecular Biology ,Receptor, Anaphylatoxin C5a ,Interleukin 4 ,biology ,integumentary system ,atopic dermatitis ,Atopic dermatitis ,Articles ,medicine.disease ,histamine ,Hairless ,Disease Models, Animal ,Endocrinology ,Oncology ,chemistry ,Neutrophil Infiltration ,C5a receptor antagonist ,Immunology ,biology.protein ,Molecular Medicine ,Interleukin-4 ,mast cell ,Histamine ,medicine.drug ,Signal Transduction - Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a genetic background. The C5a-receptor (C5aR) pathway has been reported to be involved in AD; however, the precise pathogenesis remains to be elucidated. In the present study, the contribution of the C5aR pathway to AD in mice was investigated. A BALB/c mouse model of AD was induced by application of 2,4-dinitrochlorobenzene (DNCB) onto hairless dorsal skin. Following DNCB application for 2 weeks, C5aR expression in skin tissue was assessed by reverse transcription quantitative polymerase chain reaction. C5aR expression in skin tissue was significantly increased in mice with AD. In an additional experiment, C5aR antagonist (C5aRA) intracutaneously injected in combination with DNCB treatment. The skin-fold thickness, number of total infiltrating leukocytes and mast cells infiltrating in skin tissue were measured. Interleukin-4 (IL-4) and interferon-γ (IFN-γ) levels in skin tissue and IL-4, IFN-γ, histamine and immunoglobulin E (IgE) levels in serum were measured using ELISA. The skin-fold thickness, numbers of total infiltrating leukocytes and mast cells in skin tissue, as well as levels of IL-4, IFN-γ, histamine and IgE were significantly increased in mice with AD. However, simultaneous treatment with C5aRA significantly attenuated increases in skin fold thickness and the numbers of total infiltrating leukocytes and mast cells in skin tissue. Treatment with C5aRA also decreased IL-4 and IFN-γ levels in skin tissue, as well as the levels of IL-4, IFN-γ, histamine and IgE in the serum. In conclusion, C5aRA inhibited AD in mice, possibly through suppression of the C5aR-mediated cascade action of mast cells.
- Published
- 2014