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

Nature Cell Biology volume 4, pages 2631 (2002) | Download Citation

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

    • Agatha Schwarz
    • , Sonja Ständer
    • , Markus Böhm
    • , Dagmar Kulms
    • , Karin Grosse-Heitmeyer
    •  & Thomas Schwarz
  2. Department of Dermatology, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany

    • Mark Berneburg
    •  & Jean Krutmann
  3. National Institute of Public Health and the Environment, Laboratory of Health Effects Research, 3720 BA Bilthoven, The Netherlands

    • Harry van Steeg

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Correspondence to Thomas Schwarz.

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https://doi.org/10.1038/ncb717

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