Altered expression of dermokine in skin disorders.
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 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-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.


CONCLUSIONS
These results provide novel insights into the physiological and pathological significance of dermokine in the epidermis.
Department of Dermatology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan. minoruha@derma.m.kanazawa-u.ac.jp
M
M
Hasegawa
K
K
Higashi
C
C
Yokoyama
F
F
Yamamoto
T
T
Tachibana
T
T
Matsushita
Y
Y
Hamaguchi
K
K
Saito
M
M
Fujimoto
K
K
Takehara
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000032:analysis / Q000235:genetics; D012867:Skin / Q000737:chemistry; D012871:Skin Diseases / Q000235:genetics / Q000378:metabolism*
C495568:DMKN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins