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Altered expression of dermokine in skin disorders
Author(s) -
Hasegawa M.,
Higashi K.,
Yokoyama C.,
Yamamoto F.,
Tachibana T.,
Matsushita T.,
Hamaguchi Y.,
Saito K.,
Fujimoto M.,
Takehara K.
Publication year - 2013
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/j.1468-3083.2012.04598.x
Subject(s) - proinflammatory cytokine , epidermis (zoology) , keratinocyte growth factor , keratinocyte , medicine , growth factor , pathology , keratoacanthoma , human skin , antibody , wound healing , tumor necrosis factor alpha , inflammation , transforming growth factor , epidermal growth factor , monoclonal antibody , interleukin , blot , immunology , cytokine , biology , cell culture , basal cell , receptor , gene , anatomy , biochemistry , genetics
Background Although dermokine‐β, a glycoprotein expressed in epithelial cells, does not have significant homology to other proteins, its carboxyl‐terminal domain shares a high p I value with many cytokines, suggesting similar functions. Objective To better understand the biology of dermokine, we here determined its localization under pathological conditions and examined factors that regulate its expression. Methods We generated an anti‐human dermokine‐β/γ monoclonal antibody cross‐reacting with the mouse protein. Using this antibody, immunohistological staining and Western blotting of dermokine‐β/γ were performed with various tissue samples. Results Although human dermokine‐β/γ was expressed in almost all granular layers, upper spinous layers of the skin were also stained with anti‐dermokine‐β/γ antibody in inflammatory skin disorders. Dermokine‐β/γ was expressed in keratoacanthoma and a part of well‐differentiated squamous cell carcinoma (SCC). However, dermokine‐β/γ was not detected in poorly differentiated SCC or tumours derived from non‐keratinocytes. In mice, dermokine‐β/γ‐expressed keratinocytes were increased in models of contact hypersensitivity, ultraviolet‐irradiated skin injury and wound healing. Consistent with expanded distribution in inflammatory skin diseases, proinflammatory cytokines such as interleukin‐1β, interleukin‐12, and tumour necrosis factor‐α augmented dermokine‐β/γ expression in cultured human keratinocytes. In contrast, growth factors including epidermal growth factor, insulin‐like growth factor‐I, keratinocyte growth factor and transforming growth factor‐α significantly reduced dermokine expression. Conclusion These results provide novel insights into the physiological and pathological significance of dermokine in the epidermis.