Altered expression of dermokine in skin disorders.

ABSTRACT

BACKGROUND: Although dermokine-ß, a glycoprotein expressed in epithelial cells, does not have significant homology to other proteins, its carboxyl-terminal domain shares a high pI 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-ß/γ monoclonal antibody cross-reacting with the mouse protein. Using this antibody, immunohistological staining and Western blotting of dermokine-ß/γ were performed with various tissue samples. RESULTS: Although human dermokine-ß/γ was expressed in almost all granular layers, upper spinous layers of the skin were also stained with anti-dermokine-ß/γ antibody in inflammatory skin disorders. Dermokine-ß/γ was expressed in keratoacanthoma and a part of well-differentiated squamous cell carcinoma (SCC). However, dermokine-ß/γ was not detected in poorly differentiated SCC or tumours derived from non-keratinocytes. In mice, dermokine-ß/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-1ß, interleukin-12, and tumour necrosis factor-α augmented dermokine-ß/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.