Details

Autor(en) / Beteiligte

• Pfundt, Rolph
• van Vlijmen-Willems, Ivonne
• Bergers, Mieke
• Wingens, Miriam
• Cloin, Wendy
• Schalkwijk, Joost

Titel

In situ demonstration of phosphorylated c-jun and p38 MAP kinase in epidermal keratinocytes following ultraviolet B irradiation of human skin

Ist Teil von

• The Journal of pathology, 2001-02, Vol.193 (2), p.248-255

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2001

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Ultraviolet B (UVB) irradiation is known to induce activation of cellular stress response pathways in cultured cells or intact human skin, as demonstrated by phosphorylation of MAP kinase family members and up‐ or down‐stream targets, using biochemical assays. This study demonstrates by immunohistochemistry that low‐dose UVB irradiation of normal human skin induces rapid and reversible phosphorylation of c‐jun (a target of c‐jun N‐terminal kinase) and p38 mitogen activated protein kinase (p38 MAP kinase). Phosphorylation was maximal at 4–8 h and returned to normal levels at 48 h after irradiation. Nuclear localization of these phosphorylated substrates was found using antisera against the epitope containing the phosphorylated serine‐73 of c‐jun, and the dually phosphorylated epitope (threonine‐180 and tyrosine‐182) of p38 MAP kinase. Nearly all epidermal cells were positive for c‐jun phosphorylation, whereas p38 phosphorylation was seen predominantly in the differentiated layers. In contrast to the massive activation of c‐jun and p38, only a small population of the suprabasal cells showed nuclear translocation of nuclear factor kappa B (NFκB), and a few scattered cells became apoptotic, as determined by TUNEL (TdT mediated dUTP nick end labelling) staining. The expression of involucrin and skin‐derived anti‐leukoproteinase (SKALP)/elafin, two genes putatively under control of the c‐jun and p38 pathways, was found to be increased. These findings establish the first cellular localization of UVB‐induced protein phosphorylation of stress response proteins in human epidermis, thereby providing a link between cellular activation and gene expression in defined cell populations. Copyright © 2000 John Wiley & Sons, Ltd.