Regulation of Epidermal Cell Interleukin-6 production by UV Light and Corticosteroids

Kirnbauer, Reinhard; Köck, A; Neuner, Peter; Forster, Emanuel; Krutmann, Jean; Urbanski, Agatha; Schauer, E.; Ansel, John C.; Schwarz, Thomas; Luger, Thomas A.

doi:10.1111/1523-1747.ep12470181

Cited by 175 publications

(100 citation statements)

References 39 publications

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“…This, however, does not appear to be the case, because UV light did not affect phosphorylation of STAT3, which is involved in IL-6 signaling (22,23). IL-6 is a proinflammatory cytokine whose release by keratinocytes is significantly induced by UV light and that contributes to mediation of UV light-induced local and systemic inflammation (34,35). The inability of UV light to inhibit IL-6 signaling is not surprising because it would not make sense that UV light induces the release of IL-6 on the one hand, but would prevent this cytokine from mediating its effects by interfering with its signal transduction pathway on the other.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of interferon γ-activated STAT1 by UV light

Aragane¹,

Kulms²,

Luger³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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STAT1 is a cytoplasmic transcription factor that is phosphorylated by Janus kinases (Jak) in response to interferon-␥ (IFN␥). Phosphorylated STAT1 translocates to the nucleus, where it turns on specific sets of IFN␥-inducible genes. Here, we show that UV light interferes with tyrosine phosphorylation of STAT1, thereby hindering IFN␥ from exerting its biological effects. This effect is not due to a down-regulation of the IFN␥ receptor because phosphorylation of upstream-located Jak1 and Jak2 was not suppressed by UV light. In contrast, UV light had no effect on the phosphorylation of STAT3, which is activated by the proinf lammatory cytokine interleukin 6. The UV light effect on STAT1 phosphorylation could be antagonized by vanadate, indicating at least partial involvement of a protein tyrosine phosphatase. Therefore, this study indicates a mechanism by which UV light can inhibit gene activation and suggests STAT1 as a new extranuclear UV target closely located to the membrane.

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Section: Discussionmentioning

confidence: 99%

Down-regulation of interferon γ-activated STAT1 by UV light

Aragane¹,

Kulms²,

Luger³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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“…However, no IL-10 mRNA could be detected in the RNA from NHK, maintained in the presence of this agent (data not shown). Hydrocortisone, one of the constituents of KGM, has been demonstrated to suppress IL-6 production by NHK [35]. Analysis of RNA from NHK, which were maintained in hydrocortisone-free medium, did not result in the detection of IL-10 mRNA (Fig.…”

Section: Attempts To Detect Il-10 Mrna In Nhk Via Different Approachesmentioning

confidence: 93%

In contrast to their murine counterparts, normal human keratinocytes and human epidermoid cell lines A431 and HaCaT fail to express IL-10 mRNA and protein

Teunissen¹,

Koomen²,

Jansen

et al. 1997

Clinical and Experimental Immunology

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SUMMARYIn mice, keratinocyte-derived IL-10 is up-regulated by ultraviolet-B (UVB) radiation and plays a major role in UVB-induced immunosuppression. The present study was designed to examine whether a comparable phenomenon can be detected in man. Freshly isolated or cultured normal human keratinocytes (NHK) and keratinocyte cell lines A431 and HaCaT were stimulated with graded doses of UVB (up to 200 J/m 2 ) or with a variety of other stimuli. RNA was extracted at various time points post-stimulation and analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) using four different IL-10-specific primer pairs and RNA from monocytes or T cells as positive controls. We failed to detect IL-10 mRNA in NHK from 40 different donors (breast, abdomen, leg, scalp, foreskin) and in A431 and HaCaT cells, irrespective of the stimulation used and despite successful stimulation. Supernatants of NHK, A431 and HaCaT cultures were negative for IL-10 protein, as tested by four different ELISAs and a bioassay. Murine keratinocytes, stimulated under comparable conditions and tested by the same techniques, displayed a strong expression of IL-10 mRNA and protein. Remarkably, an IL-10 mRNA signal could be detected in NHK after a second round of PCR amplification. Because NHK suspensions are contaminated with Langerhans cells, melanocytes and possibly fibroblasts, we tested pure populations of each individual cell type to determine the origin of this IL-10 mRNA. Our results clearly indicate that NHK, Langerhans cells and fibroblasts fail to express IL-10 and that melanocytes are the principal source of IL-10 mRNA in normal human epidermis.

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“…Superoxide anion release was determined on the basis of cytochrome C reduction as described (19). Briefly, cells were seeded in 3.5-cm dishes, washed twice with warm PBS and irradiated through 1 ml PBS containing 1 IL-6 was measured using the murine hybridoma cell line B9 as described (22) Electrophoretic mobility shift assay (EMSA). 1 x 106 cells were washed with PBS and detached from the dishes with a rubber policeman.…”

Section: Methodsmentioning

confidence: 99%

Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts. Evidence for increased cell viability and suppression of cytokine release.

Simon¹,

Reikerstorfer²,

Schwarz³

et al. 1995

J. Clin. Invest.

227

141

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To elucidate cellular concepts for protection against ultraviolet (UV) light we investigated the effect of heat shock protein 70 (hsp70) overexpression on cell viability and on the secretion of UV-inducible immunological cytokines. Transfected murine fibrosarcoma cells (WEHI-S), overexpressing hsp70 or a sham transfected control were used. Overexpression of hsp70 was sufficient to markedly increase cell viability upon treatment with UVB (290-320 nm). Since long wave UV (UVA, 320-400 nm) as well as UVB turned out to stimulate the release of 02 radicals we studied the cell viability upon oxidative stress. Hsp70 overexpression increased viability upon treatment with hydrogen peroxide or menadione, but had no influence on UV-induced 02 release. UV-light is known to upregulate immunologic and proinflammatory cytokines such as IL-1 and IL-6. Oxidative stress appeared to exert a similar effect. Hsp7O overexpression markedly decreased the release of IL-6 induced by UVA, UVB and oxidative stress. To test whether the hsp70 mediated suppression is confined to events caused by UVlight we determined IL-i-mediated effects. IL-1-induced IL-6 release was reduced by hsp7O overexpression, whereas the IL-1 mediated activation of nuclear factor KB was not affected. Our data suggests that hsp70 plays a central role not only in cell protection against UV-light, but also in the regulation of proinflammatory cytokine release induced by UV-exposure. (J. Clin. Invest. 1995. 95:926-933.)

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Regulation of Epidermal Cell Interleukin-6 production by UV Light and Corticosteroids

Cited by 175 publications

References 39 publications

Down-regulation of interferon γ-activated STAT1 by UV light

Down-regulation of interferon γ-activated STAT1 by UV light

In contrast to their murine counterparts, normal human keratinocytes and human epidermoid cell lines A431 and HaCaT fail to express IL-10 mRNA and protein

Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts. Evidence for increased cell viability and suppression of cytokine release.

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