Caspase 1

Caspase-1 is the effector protease of canonical inflammasomes, where inflammasome activation enables processing and secretion of IL-1β and IL-18^[1]. Mechanistically, caspase-1/11 cleaves gasdermin D (GSDMD), and GSDMD functions downstream as a pyroptosis executioner while also providing negative feedback on caspase-1/11 activation^[2]. In endothelial models, homocysteine and lipopolysaccharide induced NLRP3 inflammasome assembly, caspase-1 activation, IL-1β cleavage, and caspase-1-dependent pyroptosis linked to endothelial dysfunction^[3]. In respiratory infection models, Nontypeable Haemophilus influenzae activated caspase-1 and caspase-1 inhibition significantly reduced IL-1β release in respiratory cells and human lung tissue^[4]. Compared with related isoforms, caspase-1 primarily controlled infected macrophage pyroptosis and IL-18 production in pneumonic melioidosis, whereas caspase-11 mediated infected lung epithelial-cell pyroptosis^[5]. More broadly, murine caspase-11 and human caspase-4/5 define the noncanonical inflammasome pathway as cytosolic LPS sensors, separating their upstream recognition role from canonical procaspase-1 inflammasome activation^[6]. For experimental applications, caspase-1 inhibitors can test IL-1β-dependent inflammatory output, while GSDMD-derived peptide inhibition provides a tool to suppress caspase-1/11 activation and downstream substrate cleavage^[2][4].