title: Characterization of EGFR and ErbB2 expression in atopic dermatitis patients.
abstract: 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.
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Sääf
authors.forename: Andor
authors.initials: A
authors.lastname: Pivarcsi
authors.forename: Mårten C G
authors.initials: MC
authors.lastname: Winge
authors.forename: Carl-Fredrik
authors.initials: CF
authors.lastname: Wahlgren
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: Maria
authors.initials: M
authors.lastname: Tengvall-Linder
authors.forename: Maria
authors.initials: M
authors.lastname: Bradley
mesh_terms: D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012867:Skin / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D000075906:Chemokine CCL26; D019742:Chemokines, CC; D066246:ErbB Receptors; D018836:Inflammation Mediators; D015847:Interleukin-4; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C120429:CCL26 protein, human; C509204:PD168393; C512478:EGFR protein, human; C508053:ERBB2 protein, human