Journal article
Caspase-1 activity is required for UVB-induced apoptosis of human keratinocytes
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.1
Department of Biology, Institute for Molecular Health Science, ETH Zurich, Zurich, Switzerland.2
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. Electronic address: hans-dietmar.beer@usz.ch.3
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.
Language: | English |
---|---|
Year: | 2015 |
Pages: | 1395-1404 |
ISSN: | 0022202x and 15231747 |
Types: | Journal article |
DOI: | 10.1038/jid.2014.551 |