Caspase 5

Caspase-5 is a human inflammatory caspase and a component of the non-canonical inflammasome that senses intracellular lipopolysaccharide from Gram-negative bacteria^[1]. Mechanistically, intracellular LPS promotes rapid oligomerization of caspase-11/4/5, leading to pyroptosis and secretion of IL-1β and IL-18^[1]. In human monocytes, Pseudomonas aeruginosa outer membrane vesicles activate the noncanonical inflammasome through caspase-5, supporting its use in Gram-negative infection and OMV vaccine models^[2]. Compared with related isoforms, caspase-5, but not caspase-4, is required for inflammasome activation by P. aeruginosa OMVs, whereas transfected free LPS induces inflammasome responses through caspase-4^[2]. Therefore, caspase-4 and caspase-5 differentially recognize LPS depending on physical form or route of delivery into the cell^[2]. Current retrieved evidence supports caspase-5 pathway studies using OMVs, CRISPR/Cas9 knockout THP-1 cells, IL-1β release, caspase-1 cleavage, and pyroptosis readouts, but does not establish a selective caspase-5 agonist or inhibitor^[2].