title: Tumor necrosis factor beta and ultraviolet radiation are potent regulators of human keratinocyte ICAM-1 expression.
abstract: Intercellular adhesion molecule-1 (ICAM-1) functions as a ligand of leukocyte function-associated antigen-1 (LFA-1), as well as a receptor for human picorna virus, and its regulation thus affects various immunologic and inflammatory reactions. The weak, constitutive ICAM-1 expression on human keratinocytes (KC) can be up-regulated by cytokines such as interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha). In order to further examine the regulation of KC ICAM-1 expression, normal human KC or epidermoid carcinoma cells (KB) were incubated with different cytokines and/or exposed to ultraviolet (UV) radiation. Subsequently, ICAM-1 expression was monitored cytofluorometrically using a monoclonal anti-ICAM-1 antibody. Stimulation of cells with recombinant human (rh) interleukin (IL) 1 alpha, rhIL-4, rhIL-5, rhIL-6, rh granulocyte/macrophage colony-stimulating factor (GM-CSF), rh interferon alpha (rhIFN alpha), and rh transforming growth factor beta (TGF beta) did not increase ICAM-1 surface expression. In contrast, rhTNF beta significantly up-regulated ICAM-1 expression in a time- and dose-dependent manner. Moreover, the combination of rhTNF beta with rhIFN gamma increased the percentage of ICAM-1-positive KC synergistically. This stimulatory effect of rhTNF beta was further confirmed by the demonstration that rhTNF beta was capable of markedly enhancing ICAM-1 mRNA expression in KC. Finally, exposure of KC in vitro to sublethal doses of UV radiation (0-100 J/m2) prior to cytokine (rhIFN tau, rhTNF alpha, rhTNF beta) stimulation inhibited ICAM-1 up-regulation in a dose-dependent fashion. These studies identify TNF beta and UV light as potent regulators of KC ICAM-1 expression, which may influence both attachment and detachment of leukocytes and possibly viruses to KC.
authors.affiliation: Department of Dermatology, University of Freiburg, FRG.
authors.forename: J
authors.initials: J
authors.lastname: Krutmann
authors.forename: A
authors.initials: A
authors.lastname: Köck
authors.forename: E
authors.initials: E
authors.lastname: Schauer
authors.forename: F
authors.initials: F
authors.lastname: Parlow
authors.forename: A
authors.initials: A
authors.lastname: Möller
authors.forename: A
authors.initials: A
authors.lastname: Kapp
authors.forename: E
authors.initials: E
authors.lastname: Förster
authors.forename: E
authors.initials: E
authors.lastname: Schöpf
authors.forename: T A
authors.initials: TA
authors.lastname: Luger
mesh_terms: D001685:Biological Factors / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007378:Interleukins / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D011991:Receptors, Virus / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D001685:Biological Factors; D015815:Cell Adhesion Molecules; D003115:Colony-Stimulating Factors; D016207:Cytokines; D006133:Growth Substances; D007378:Interleukins; D008233:Lymphotoxin-alpha; D011991:Receptors, Virus; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor