Ultraviolet radiation effects on human keratinocyte ICAM-1 expression: UV-induced inhibition of cytokine-induced ICAM-1 mRNA expression is transient, differentially restored for IFN gamma versus TNF alpha, and followed by ICAM-1 induction via a TNF alpha-like pathway.
Human keratinocytes (KC) during the course of inflammatory dermatoses strongly express the surface molecule ICAM-1, which plays an important role in the generation of the epidermal inflammatory infiltrate by mediating leukocyte-keratinocyte interactions. Accordingly, KC ICAM-1 expression is known to be induced in vivo and in vitro by cytokines either via the TNF alpha/TNF beta or via the IFN gamma-mediated pathway. In contrast, ultraviolet (UV) radiation previously has been found to potently inhibit cytokine-induced KC ICAM-1 surface expression by a sublethal mechanism. In order to further define this novel immunosuppressive effect of UV light, the effects of in vitro UV radiation on ICAM-1 mRNA expression in transformed human KC (KB cells) were examined. Accordingly, UV light (0-100 J/m2) inhibited IFN gamma- as well as TNF alpha-induced ICAM-1 mRNA expression, if KC were cytokine stimulated immediately after irradiation. After a 12-h incubation period, however, IFN gamma responsiveness was found to be restored in irradiated cells, whereas restoration of responsiveness to TNF alpha required at least a 24-h recovery phase. Moreover, UV light alone did not alter ICAM-1 mRNA levels after 4, 12, or 24 h. After 48 h, however, a significant increase in ICAM-1 mRNA and surface expression in UV-irradiated KC could be observed. In addition, this increase could be superinduced by stimulation of irradiated KC with IFN gamma, but not with TNF alpha. UV-induced upregulation of ICAM-1 expression could be mimicked by stimulating unirradiated cells with supernatants derived from UV-irradiated cells. Addition of biologically active anti-TNF alpha antibodies to UV-irradiated cells or to supernatants derived from UV-irradiated KC, however, did not even partially abolish this ICAM-1-inducing activity. UV light thus seems to affect KC ICAM-1 mRNA expression in a biphasic manner: an early period of inhibition of cytokine-induced ICAM-1 expression is transient and followed by restoration of responsiveness to ICAM-1-inducing cytokines. Moreover, UV itself is able to induce ICAM-1 mRNA expression at this later time point via a TNF alpha-like pathway. These studies identify UV irradiation as a potent modulator of cytokine regulated ICAM-1 gene transcription with the capacity to induce both inhibitory as well as enhancing effects.
Department of Dermatology, University of Freiburg, F.R.G.
J
J
Krutmann
W
W
Czech
F
F
Parlow
U
U
Trefzer
A
A
Kapp
E
E
Schöpf
T A
TA
Luger
D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D005434:Flow Cytometry; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014466:Ultraviolet Rays
D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma