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Interleukin-12 suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair

Nature Cell Biology volume 4, pages 26–31 (2002)Cite this article

Abstract

Induction of apoptosis of keratinocytes by ultraviolet (UV) radiation is a protective phenomenon relevant in limiting the survival of cells with irreparable DNA damage. Changes in UV-induced apoptosis may therefore have significant impact on photocarcinogenesis. We have found that the immunomodulatory cytokine IL-12 suppresses UV-mediated apoptosis of keratinocytes both in vitro and in vivo. IL-12 caused a remarkable reduction in UV-specific DNA lesions which was due to induction of DNA repair. In accordance with this, IL-12 induced the expression of particular components of the nucleotide-excision repair complex. Our results show that cytokines can protect cells from apoptosis induced by DNA-damaging UV radiation by inducing DNA repair, and that nucleotide-excision repair can be manipulated by cytokines.

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Figure 1: IL-12 inhibits UVB-induced apoptosis.
Figure 2: IL-12 reduces UVB-induced DNA damage.
Figure 3: IL-12 reduces UVB-induced DNA damage in vivo.
Figure 4: In vivo reduction of SCs by IL-12.
Figure 5: Increased number of SCs in IL-12 knockout mice.
Figure 6: IL-12 enhances comet length in UV-exposed cells.
Figure 7: IL-12 does not reduce the number of SCs in Xpa knockout mice.
Figure 8: IL-12 does not reduce UVB-induced DNA damage in XP cells.

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Acknowledgements

We thank I. Förster and M. Röcken for help in obtaining IL-12/p40 knockout mice, B. Pöppelmann and I. Wolff for excellent technical assistance, H. Riemann for help with phosphorimager analysis and O. Micke for assistance in carrying out γ-irradiation. This work was supported by grants from the German Research Foundation (Schw 625/1–3), the Interdisciplincary Center for Clinical Research (IZKF, E10) and the Federal Ministery of Education and Research (07UVB63A/5) to T.S. M.B. is supported by the German Research Foundation (Emmy Noether-Programm BE 2005/2–1).

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Authors and Affiliations

  1. Department of Dermatology, Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Münster, Von-Esmarchstrasse 58, Münster, D-48149, Germany

    Agatha Schwarz, Sonja Ständer, Markus Böhm, Dagmar Kulms, Karin Grosse-Heitmeyer & Thomas Schwarz

  2. Department of Dermatology, University of Düsseldorf, Moorenstrasse 5, Düsseldorf, D-40225, Germany

    Mark Berneburg & Jean Krutmann

  3. National Institute of Public Health and the Environment, Laboratory of Health Effects Research, Bilthoven, 3720, BA, The Netherlands

    Harry van Steeg

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Schwarz, A., Ständer, S., Berneburg, M. et al. Interleukin-12 suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair. Nat Cell Biol 4, 26–31 (2002). https://doi.org/10.1038/ncb717

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