Tumor necrosis factor β and ultraviolet radiation are potent regulators of human keratinocyte ICAM-1 expression

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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 (IFNγ) and tumor necrosis factor alpha (TNFα). 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) α, rhIL-4, rhIL-5, rhIL-6, rh granulocyte/macrophage colonystimulating factor (GM-CSF), rh interferon alpha (rhIFNα), and rh transforming growth factor beta (TGFβ) did not increase ICAM-1 surface expression. In contrast, rhTNFβ significantly up-regulated ICAM-1 expression in a time- and dose-dependent manner. Moreover, the combination of rhTNFβ with rhIFNγ increased the percentage of ICAM-1-positive KC synergistically. This stimulatory effect of rhTNFβ was further confirmed by the demonstration that rhTNFβ 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 (rhIFNτ, rhTNFα, rhTNFβ) stimulation inhibited ICAM-1 up-regulation in a dose-dependent fashion. These studies identify TNFβ 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. © 1990.

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Krutmann, J., Köck, A., Schauer, E., Parlow, F., Möller, A., Kapp, A., … Luger, T. A. (1990). Tumor necrosis factor β and ultraviolet radiation are potent regulators of human keratinocyte ICAM-1 expression. Journal of Investigative Dermatology, 95(2), 127–131. https://doi.org/10.1111/1523-1747.ep12477839

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