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

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-1?). Thus, in addition to its role as a danger signal, which occurs when the cytokine is passively released by cell necrosis, IL-1? 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-1? acetylation. To demonstrate the physiological significance of this newly discovered mechanism, we used IL-1? knockout mice and show that IL-1? 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.

SUBMITTER: Cohen I 

PROVIDER: S-EPMC4593953 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature