Journal Article

Caspase-1 Activity Is Required for UVB-Induced Apoptosis of Human Keratinocytes

Grossi, Serena, French, Lars E., Beer, Hans-Dietmar, Garstkiewicz, Martha, Sollberger, Gabriel, Strittmatter, Gerhard E., auf dem Keller, Ulrich

2015

Overview

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.

• Publisher: Elsevier Inc
• Subject: Animals / Apoptosis - radiation effects / Caspase 1 - drug effects / Caspase 1 - genetics / Caspase 1 - metabolism / Caspases, Initiator - metabolism / Cells, Cultured / Female / Humans / Inflammasomes - metabolism / Keratinocytes - metabolism / Keratinocytes - pathology / Keratinocytes - radiation effects / Male / Membrane Proteins - metabolism / Mice / Mice, Knockout / Models, Animal / RNA, Small Interfering - pharmacology / Skin Neoplasms - pathology / Skin Neoplasms - prevention & control / Ultraviolet Rays - adverse effects