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Sci Rep. 2015 Oct 6;5:14756. doi: 10.1038/srep14756.

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

Author information

1
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, INSERM U 964, Université de Strasbourg, 67404 Illkirch, France.
2
Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
3
The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, 84105 Beer-Sheva, Israel.
4
Bioimaging Center and Center for Applied Photonics, Department of Biology and Department of Physics, University of Konstanz, Konstanz, Germany.
5
Department of Dermatology, Medical Center and Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
6
BIOSS, Faculty of Biology III, University of Freiburg, Freiburg, Germany.
7
University of Colorado Denver, Aurora, CO USA.

Abstract

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.

PMID:
26439902
PMCID:
PMC4593953
DOI:
10.1038/srep14756
[Indexed for MEDLINE]
Free PMC Article

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