Characterization of EGFR and ErbB2 expression in atopic dermatitis patients

Autor: Mårten C.G. Winge, Annika Sääf, Magnus Nordenskjöld, Maria Tengvall-Linder, Maria Bradley, Bernhard Homey, Andor Pivarcsi, Carl-Fredrik Wahlgren
Rok vydání: 2012
Předmět:
Zdroj: Archives of Dermatological Research. 304:773-780
ISSN: 1432-069X
0340-3696
DOI: 10.1007/s00403-012-1242-4
Popis: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases in industrialized countries. To identify candidate genes involved in the pathogenesis of AD, we previously undertook a genome-wide approach using DNA microarrays. A transcript encoding the epidermal growth factor receptor (EGFR) was found to be among the down-regulated transcripts in AD skin. Here, we further investigated the expression pattern of two EGFR family members (EGFR and ErbB2) in AD skin on a protein level. Immunohistochemical (IHC) analysis of EGFR and ErbB2 showed decreased expression of EGFR and ErbB2 proteins in AD lesional skin as compared to skin from healthy individuals. Interestingly, we found that EGFR and ErbB2 were reciprocally expressed in an in vitro model of keratinocyte proliferation and differentiation, paralleling the expression patterns found in epidermis of healthy skin. The highest levels of EGFR transcripts were found in proliferating cells, while ErbB2 was found in differentiated cells. We show that blocking EGFR activity combined with co-stimulation of the Th2-cytokine IL4 in keratinocytes leads to induction of the inflammatory chemokine CCL26/eotaxin-3 in vitro. Accordingly, increased CCL26 transcriptional levels were observed in AD lesional skin. Taken together, suppression of EGFR may contribute to the pathogenesis of AD via the regulation of inflammatory chemokines.
Databáze: OpenAIRE
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