Caspase‐5 rescues UVB‐dependent IL‐1β activity in ASC‐deficient epidermal keratinocytes

To the Editor, IL-1b is a potent phlogistic mediator induced in inflammatory skin diseases, which is activated by several environmental triggers (1–3). In epidermal keratinocytes, pro-inflammatory IFN-c regulates proteolytic caspases, which are activated by UVB irradiation to cleave IL-1b (4). Apoptosis-associated speck-like protein containing a CARD (ASC) is an adaptor protein, which is required for activation of UVB-dependent IL-1b release by caspase-1 (2, 5). However, an inducible IL-1b production in ASC-deficient mouse keratinocytes indicates that the cells inherit the capacity for ASC-independent IL-1b activation (6). Inflammatory caspase-5 functions independently of ASC to activate IL-1b (7, 8), and we hypothesized that caspase-5 can rescue an UVB-induced IL-1b production in the absence of ASC. In an experimental model for UVB-triggered inflammation, cultured keratinocytes were UVB-irradiated in the presence of IFN-c to induce an IL-1b release into the supernatant as measured by ELISA. Under these conditions, ASC levels remained unaffected [Fig. 1a; (2)] but when ASC was simultaneously suppressed by siRNA interference (Fig. 1b), IL-1b was induced and increasingly released by keratinocytes (Fig. 1c,d). Data indicated an IL-1b-promoting mechanism independent of ASC, and the regulation of IL-1b-converting caspases