Tumor Necrosis Factor β and Ultraviolet Radiation Are Potent Regulators of Human Keratinocyte ICAM-1 Expression

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 KG ICAM-1 expression, normal human KC or epidermoid carcinoma cells (KB) were incubated with different cytokines and/or exposed to ultraviolet (UV) radiation. Subsequently, IGAM-1 expression was monitored cytofluorometrically using a monoclonal anti-IGAM-1 antibody. Stimulation of cells with recombinant human (rh) interleukin (IL) 1α, rhIL-4, rhIL-5, rhIL-6, rh granulocyte/macrophage colony-stimulating 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 [AM-i 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 TNFIJ 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