Caspase 4

Caspase-4 is a human inflammatory caspase that directly senses cytosolic lipopolysaccharide and activates non-canonical inflammasome signaling^[1]. Mechanistically, activated caspase-4 cleaves gasdermin D, whose N-terminal fragment forms membrane pores that drive pyroptosis and support inflammatory cytokine release^[2]. In human macrophage models, Shiga toxin 2/LPS activates caspase-4, GSDMD, mitochondrial ROS, and the NLRP3 inflammasome to promote IL-1β production and pyroptosis^[3]. Caspase-4 also interacts with TRAF6 and mediates LPS-induced NF-κB-dependent production of IL-8 and CCL4 in THP-1 monocytic cells^[4]. Compared with related isoforms, caspase-4 and caspase-5 are human orthologues of murine caspase-11, but caspase-4 detects tetra-acylated LPS and cytosolic Francisella novicida in human macrophages^[5]. In human monocytes, caspase-4 and caspase-5 mediate IL-1α and IL-1β release after LPS stimulation, while caspase-5 undergoes rapid processing and caspase-4 remains uncleaved^[6]. For experimental applications, intracellular LPS serves as a caspase-4 agonistic trigger, whereas LEVD-fmk and Ac-FLTD-CMK have been used to suppress caspase-4/5 or caspase-4-associated inflammasome activation^[6][7].- Caspase-4 links cytosolic LPS sensing to GSDMD cleavage, pyroptosis, and cytokine release^[1][2]. - Caspase-4 differs from caspase-5 by activation behavior, pathogen sensing, and cleavage status^[5][6].