title: Caspase-1 activity is required for UVB-induced apoptosis of human keratinocytes.
abstract: 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.
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Sollberger
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Gerhard E
authors.initials: GE
authors.lastname: Strittmatter
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Serena
authors.initials: S
authors.lastname: Grossi
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Martha
authors.initials: M
authors.lastname: Garstkiewicz
authors.affiliation: Department of Biology, Institute for Molecular Health Science, ETH Zurich, Zurich, Switzerland.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Auf dem Keller
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Lars E
authors.initials: LE
authors.lastname: French
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. Electronic address: hans-dietmar.beer@usz.ch.
authors.forename: Hans-Dietmar
authors.initials: HD
authors.lastname: Beer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D020170:Caspase 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D053471:Caspases, Initiator / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D034741:RNA, Small Interfering / Q000494:pharmacology; D012878:Skin Neoplasms / Q000473:pathology / Q000517:prevention & control; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C091247:BCAP31 protein, human; D058847:Inflammasomes; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C093516:CASP4 protein, human; D053471:Caspases, Initiator; D020170:Caspase 1