title: Caspase-1: an integral regulator of innate immunity.
abstract: Caspase-1 is a unique cysteine protease playing central roles in innate immunity. Pathogens, stress, and damage signals induce activation of caspase-1, typically mediated by proximity-induced autoproteolysis in multimeric protein complexes called the inflammasome. Active caspase-1 induces secretion of pro-inflammatory cytokines and mediates pyroptosis, a programmed pro-inflammatory cell death, thereby initiating an immune response finally leading to pathogen clearance. Excessive activation of caspase-1 is the underlying cause for rare diseases such as periodic fever syndromes, and more common disorders, including atherosclerosis, type 2 diabetes, and gout. Beside these well-known pro-inflammatory functions, active caspase-1 also has anti-inflammatory and protective functions contributing to cell survival, reduced inflammatory cytokine signaling, and improved outcomes in mouse models of burn injury or trauma and shock. Furthermore, naturally occurring procaspase-1 variants with reduced or abrogated enzymatic activity mediate enhanced inflammatory signaling and have been associated to autoinflammatory symptoms. Here, we review functions of caspase-1 focusing on anti-inflammatory signaling pathways and discuss the role of enzymatically inactive caspase-1 as disease-promoting factors in autoinflammatory diseases. Moreover, we illustrate differential requirements for autoproteolysis and enzymatic activity in caspase-1 functions.
authors.affiliation: Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Winkler
authors.forename: Angela
authors.initials: A
authors.lastname: Rösen-Wolff
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007113:Immunity, Innate; D056747:Immunomodulation; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D059748:Proteolysis
chemical_list: D020170:Caspase 1