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01-07-2015 | Review

Caspase-1: an integral regulator of innate immunity

Authors: Stefan Winkler, Angela Rösen-Wolff

Published in: Seminars in Immunopathology | Issue 4/2015

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.

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Title: Caspase-1: an integral regulator of innate immunity
Authors: Stefan Winkler
Angela Rösen-Wolff
Publication date: 01-07-2015
Publisher: Springer Berlin Heidelberg
Published in: Seminars in Immunopathology / Issue 4/2015
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-015-0494-4

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