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

Gabriel Sollberger, Gerhard E. Strittmatter, Serena Grossi, Martha Garstkiewicz, Ulrich auf dem Keller, Lars E. French, Hans-Dietmar Beer (Lead / Corresponding author)

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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.

Original languageEnglish
Pages (from-to)1395-1404
Number of pages10
JournalJournal of Investigative Dermatology
Volume135
Issue number5
Early online date29 Jan 2015
DOIs
Publication statusPublished - 22 May 2015

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    Sollberger, G., Strittmatter, G. E., Grossi, S., Garstkiewicz, M., auf dem Keller, U., French, L. E., & Beer, H-D. (2015). Caspase-1 activity is required for UVB-induced apoptosis of human keratinocytes. Journal of Investigative Dermatology, 135(5), 1395-1404. https://doi.org/10.1038/jid.2014.551