title: Cytokine-induced expression of transforming growth factor-alpha and the epidermal growth factor receptor in neonatal skin explants.
abstract: Hyperproliferative diseases of the epidermal keratinocytes, such as psoriasis vulgaris, are characterized by overexpression and altered distribution of the epidermal growth factor/transforming growth factor (EGF/TGF)-alpha receptor, and of TGF-alpha itself. It is believed that overexpression of this lignad/receptor system contributes to the hyperproliferative state of keratinocytes in an autocrine fashion. However, little is known about the factors that regulate expression of the EGF/TGF-alpha receptor, as well as expression of TGF-alpha in stratified epithelium. We examined modulation of the immunoreactive EGF/TGF-alpha receptor and TGF-alpha expression in normal neonatal foreskin explants by a variety of cytokines present in psoriatic lesions. Human (hu) recombinant (r) tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma induced EGF/TGF-alpha receptor and TGF-alpha expression by keratinocytes as determined by immunohistochemistry. Neutralizing antibodies to TNF-alpha and IFN-gamma inhibited upregulation of EGF/TGF-alpha receptors and TGF-alpha by the respective cytokines. Interleukin (IL)-8 induced expression of TGF-alpha, but not of its receptor. Other cytokines (TNF-beta, IFN-beta, IL-1 alpha, IL-2, IL-3, IL-5, IL-6, granulocyte/macrophage colony-stimulating factor, and macrophage colony-stimulating factor) did not alter the expression patterns of EGF/TGF-alpha receptors or TGF-alpha in normal neonatal skin explants. These experiments demonstrate that specific cytokines known to be present in psoriatic lesions can induce normal epidermis to express TGF-alpha and its receptor in a pattern similar to that observed in psoriatic skin.
authors.affiliation: Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
authors.forename: I
authors.initials: I
authors.lastname: Valyi-Nagy
authors.forename: P J
authors.initials: PJ
authors.lastname: Jensen
authors.forename: S M
authors.initials: SM
authors.lastname: Albelda
authors.forename: U
authors.initials: U
authors.lastname: Rodeck
mesh_terms: D016207:Cytokines / Q000494:pharmacology*; D066246:ErbB Receptors / Q000032:analysis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D009924:Organ Culture Techniques; D012867:Skin / Q000737:chemistry* / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D016209:Interleukin-8; D016211:Transforming Growth Factor alpha; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D066246:ErbB Receptors