IL-1α is a DNA damage sensor linking genotoxic stress signaling to sterile inflammation and innate immunity

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2015
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Cohen, Idan
Rider, Peleg
Voronov, Elena
Tudor, Cicerone
Wegner, Mareike
Brondani, Lydia
Apte, Ron N.
Schneider, Robert
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Scientific Reports. 2015, 5, 14756. eISSN 2045-2322. Available under: doi: 10.1038/srep14756
Zusammenfassung

Environmental signals can be translated into chromatin changes, which alter gene expression. Here we report a novel concept that cells can signal chromatin damage from the nucleus back to the surrounding tissue through the cytokine interleukin-1alpha (IL-1α). Thus, in addition to its role as a danger signal, which occurs when the cytokine is passively released by cell necrosis, IL-1α could directly sense DNA damage and act as signal for genotoxic stress without loss of cell integrity. Here we demonstrate localization of the cytokine to DNA-damage sites and its subsequent secretion. Interestingly, its nucleo-cytosolic shuttling after DNA damage sensing is regulated by histone deacetylases (HDAC) and IL-1α acetylation. To demonstrate the physiological significance of this newly discovered mechanism, we used IL-1α knockout mice and show that IL-1α signaling after UV skin irradiation and DNA damage is important for triggering a sterile inflammatory cascade in vivo that contributes to efficient tissue repair and wound healing.

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ISO 690COHEN, Idan, Peleg RIDER, Elena VORONOV, Martin TOMAS, Cicerone TUDOR, Mareike WEGNER, Lydia BRONDANI, Elisa FERRANDO-MAY, Ron N. APTE, Robert SCHNEIDER, 2015. IL-1α is a DNA damage sensor linking genotoxic stress signaling to sterile inflammation and innate immunity. In: Scientific Reports. 2015, 5, 14756. eISSN 2045-2322. Available under: doi: 10.1038/srep14756
BibTex
@article{Cohen2015-10-06damag-35182,
  year={2015},
  doi={10.1038/srep14756},
  title={IL-1α is a DNA damage sensor linking genotoxic stress signaling to sterile inflammation and innate immunity},
  volume={5},
  journal={Scientific Reports},
  author={Cohen, Idan and Rider, Peleg and Voronov, Elena and Tomas, Martin and Tudor, Cicerone and Wegner, Mareike and Brondani, Lydia and Ferrando-May, Elisa and Apte, Ron N. and Schneider, Robert},
  note={Article Number: 14756}
}
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