Intradermal transfer of caspase-1 (CASP1) DNA into mouse dissects:: role of CASP1 in interleukin-1β associated skin inflammation and apoptotic cell death

Caspase-1 (CASP1)/interleukin-1 beta (IL-1 beta) converting enzyme (ICE) has been cloned as a specific enzyme which activates the biologically inactive pro-form of IL-1 beta into biological active IL-1 beta. Based on the significant homology to ced-3, Caenorhabditis elegans apoptotic gene and, proof of apoptotic activity of ICE in rat fibroblasts, ICE was renamed as CASP1. In contrast to in vitro functions, the in vivo significance of high expression of CASP1 in skin remains to be elucidated. We transferred plasmid DNA encoding murine CASP1 with beta-actin promoter into mouse skin. The CASP1 DNA-injected skin, but not skin injected with control plasmid without CASP1, developed localized erythema with subcutaneous nodules, The nodules were associated with marked inflammatory infiltrates. The apoptotic cells detected by the TUNEL method were distributed in and around the inflammatory foci. The plasma IL-1 beta level of CASP1 DNA-injected mouse was elevated compared with that of the control DNA-injected mouse. These inflammatory reactions of CASP1 DNA-injected skin were suppressed by treatment with neutralizing anti-murine IL-1 beta antibodies, but the TUNEL, positive apoptotic cells were still detected. This study clearly demonstrate dual roles of CASP1 in causing IL-1 beta associated granulomatous skin infiltration and inducing apoptotic cell death in vivo. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.