Ultraviolet B induces proteolytic cleavage of the pyroptosis inducer gasdermin E in keratinocytes

Pyroptosis is a form of regulated cell death (RCD, in contrast to accidental cell death) initiated by challenges of homeostasis, and previous evidence had indicated that it is closely related to innate immune response, e.g., upon pathogen invasion [ [1] Jorgensen I. Miao E.A. Pyroptotic cell death defends against intracellular pathogens. Immunological reviews. 2015; 265: 130-142 Crossref PubMed Scopus (395) Google Scholar ]. Pyroptosis presents a special morphological feature of cell swelling and culminates with plasma membrane permeabilization [ [2] Galluzzi L. Vitale I. Aaronson S.A. Abrams J.M. Adam D. Agostinis P. et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell death and differentiation. 2018; 25 (2018): 486-541 Crossref PubMed Scopus (1573) Google Scholar ]. The gasdermin family includes gasdermin A (GSDMA), GSDMB, GSDMC, GSDMD, GSDME (also known as DFNA5), and PJVK (also known as DFNB59). They share approximately 45% sequence identity. Except for PJVK, the gasdermin family members adopt a two-domain architecture, and their gasdermin-N domains exhibit similar pore-forming activity to induce pyroptosis [ [3] Shi J. Gao W. Shao F. Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death. Trends in biochemical sciences. 2017; 42: 245-254 Abstract Full Text Full Text PDF PubMed Scopus (633) Google Scholar ]. Thus, pyroptosis is defined as a type of RCD that critically depends on the formation of a plasma membrane perforated by the gasdermin family, often (but not always) as a consequence of inflammatory caspase activation [ [2] Galluzzi L. Vitale I. Aaronson S.A. Abrams J.M. Adam D. Agostinis P. et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell death and differentiation. 2018; 25 (2018): 486-541 Crossref PubMed Scopus (1573) Google Scholar ]. Ultraviolet exposure is a major pathogenic factor for human skin, and ultraviolet B (UVB)-induced keratinocyte apoptosis (one RCD) is a critical mechanism to preserve genomic integrity for preventing photocarcinogenesis. However, whether UVB triggers pyroptosis in keratinocytes remains unknown.