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

Cohen, I., Rider, P., Vornov, E., Tomas, M., Tudor, C., Wegner, M., et al. (2015). IL-1α is a DNA damage sensor linking genetoxic stress signaling to sterile inflammation and innate immunity. Scientific Reports, 5, 1-11.

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 Creators:
Cohen, Idan1, Author           
Rider, Peleg2, Author
Vornov, Elena2, Author
Tomas, Martin3, Author
Tudor, Cicerone4, Author
Wegner, Mareike5, Author
Brondani, Lydia6, Author
Freudenberg, Marina7, Author           
Mittler, G.8, Author           
Elisa, Ferrando-May3, Author
Dinarello, Charles A.9, Author
Apte, Ron N.2, Author
Schneider, Robert6, Author
Affiliations:
1Spemann Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243655              
2The Sharga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel, ou_persistent22              
3Bioimaging Center and Center for Applied Photonics, Department of Biology and Department, University of Konstanz, Konstanz, Germany, ou_persistent22              
4Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              
5Department of Dermatology, Medical Center and Faculty of Biology, University of Freiburg, Freiburg, Germany, ou_persistent22              
6Institut de Génétique et de Biologie Moléculaire, CNRS UMR 7104, INSERM U 964, Université de Strasbourg, Illkirch, France, ou_persistent22              
7Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243647              
8Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
9University of Colorado Denver, Aurora, CO, USA, ou_persistent22              

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 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.

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Language(s): eng - English
 Dates: 2015-10-06
 Publication Status: Published in print
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: -
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Title: Scientific Reports
Source Genre: Journal
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Pages: 11 Volume / Issue: 5 Sequence Number: - Start / End Page: 1 - 11 Identifier: -