PuSH - Publikationsserver des Helmholtz Zentrums München

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)
DOI Verlagsversion bestellen
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.
Weitere Metriken?
Zusatzinfos bearbeiten [➜Einloggen]
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