Caspase-1 activity is required for UVB-induced apoptosis of human keratinocytes

Caspase-1 has a crucial role in innate immunity as the protease activates the proinflammatory cytokine prointerleukin(IL)-1β. Furthermore, Caspase-1 induces Pyroptosis, a lytic form of cell death that supports inflammation. Activation of Caspase-1 occurs in multi-protein complexes termed inflammasomes, which assemble upon sensing of stress signals. In the skin and in skin-derived keratinocytes, UVB irradiation induces inflammasome-dependent IL-1 secretion and sunburn. Here we present evidence that Caspase-1 and caspase-4 are required for UVB-induced Apoptosis. In UVB-irradiated human primary keratinocytes, Apoptosis occurs significantly later than inflammasome activation but depends on Caspase-1 activity. However, it proceeds independently of inflammasome activation. By a proteomics approach, we identified the antiapoptotic Bap31 as a putative Caspase-1 substrate. Caspase-1-dependent Apoptosis is possibly a recent process in evolution as it was not detected in mice. These results suggest a protective role of Caspase-1 in keratinocytes during UVB-induced skin Cancer development through the induction of Apoptosis.