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Cohen, I.R.* ; Peleg, R.* ; Voronov, E.* ; Tomas, M.* ; Tudor, C.* ; Wegner, M.* ; Brodabi, L.* ; Freudenberg, M.* ; Mittler, G.* ; Ferrando-May, E.* ; Dinarello, C.A.* ; Apte, R.N.* ; Schneider, R.*

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

Sci. Rep. 5:14756 (2015)
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Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 5, Heft: , Seiten: , Artikelnummer: 14756 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed