The expression of endothelin-1 and its binding sites in mouse skin increased after ultraviolet B irradiation or local injection of tumor necrosis factor alpha.
Endothelin (ET)-1 is a 21-amino acid peptide which has vasoconstrictor and growth regulatory activity. Recently, cultured keratinocytes have been reported to express ET-1 and its receptor when irradiated by ultraviolet (UV) B. In order to further understand the role of ET-1 in vivo during UVB-induced inflammation, we examined the localization, intensity and time course of the expression levels of ET-1 and its binding sites in UVB-exposed BALB/c mouse skin. Frozen and paraffin sections prepared from mouse skin 48 h after treatment with UVB irradiation (0.36 or 0.72 J/cm2) or after injection with tumor necrosis factor (TNF)-alpha (1.0 microgram) or interleukin (IL)-1 alpha (0.05 microgram) were incubated with monoclonal anti-ET-1 IgG and then visualized by peroxidase staining. In normal skin, faint ET-1 immunoreactivity was observed in the epidermis, pilosebaceous structures and blood vessels. Upon exposure to UVB irradiation or administration of TNF-alpha injection or IL-1 alpha injection, such immunoreactivity was found to be significantly enhanced. Subsequently, the frozen sections were incubated with 125I ET-1 for 30 min, and visualized by autoradiographic technique. In normal skin, ET-1 weakly bound to the skin, while UVB irradiation and TNF-alpha injection significantly enhanced ET-1 binding in the epidermis, pilosebaceous structures and blood vessels. Time course experiments (1, 2, 4 and 7 days) indicated that ET-1 immunoreactivity and ET-1 binding peaked 1 or 2 days after UVB irradiation or TNF-alpha injection. These results suggest that the up-regulated expression of ET-1 and its binding sites in the epidermis and pilosebaceous structures may act as an autocrine/paracrine factor during UVB-induced inflammation.
Ahn
G Y
GY
Department of Dermatology, Juntentendo University School of Medicine, Tokyo, Japan.
Butt
K I
KI
Jindo
T
T
Yaguchi
H
H
Tsuboi
R
R
Ogawa
H
H
D000818:Animals; D001665:Binding Sites; D046508:Culture Techniques; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000032:analysis*; D007150:Immunohistochemistry; D007271:Injections, Intradermal; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012016:Reference Values; D012867:Skin / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014466:Ultraviolet Rays
D019332:Endothelin-1; D014409:Tumor Necrosis Factor-alpha