TITLE

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

AUTHOR(S)
Idan, Cohen; Peleg, Rider; Elena, Voronov; Martin, Tomas; Cicerone, Tudor; Mareike, Wegner; Lydia, Brondani; Marina, Freudenberg; Gerhard, Mittler; Elisa, Ferrando-May; Dinarello, Charles A.; Ron, Apte N.; Robert, Schneider
PUB. DATE
October 2015
SOURCE
Scientific Reports;10/9/2015, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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.
ACCESSION #
110327903

 

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