Complex roles of caspases in the pathogenesis of inflammatory bowel disease

Becker, Christoph, Watson, Alastair J and Neurath, Markus F (2013) Complex roles of caspases in the pathogenesis of inflammatory bowel disease. Gastroenterology, 144 (2). pp. 283-93. ISSN 0016-5085

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Abstract

Caspases are cysteine proteases that regulate embryonic development, cell differentiation, tissue homoeostasis, and removal of damaged and harmful cells from the intestine and other parts of the body. Caspase activity is mainly regulated at the posttranslational level, which allows their rapid activation and response to cellular stress and pathogenic stimuli. In most cell types, caspases are initially expressed as inactive proenzymes, which undergo proteolytic cleavage to become functional enzymes. Caspase dysfunction has been associated with intestinal diseases, including inflammatory bowel disease (IBD) and colorectal cancer. Although the roles of caspases have been studied extensively in regulation of apoptosis, recent discoveries have highlighted cell death-independent functions of this protein family. In particular, caspase-1, caspase-4, caspase-5, and caspase-12 are activated during innate immune responses and participate in the formation of the inflammasome. Caspase-8 controls necroptosis of Paneth cells and potentially the death of intestinal epithelial cells in patients with Crohn's disease and appears to be involved in mucosal inflammation. Regulators of caspase-8 might therefore be used to prevent cell death in patients with IBD. Improving our understanding of the regulation and function of caspases in the intestine might lead to new therapeutics for chronic intestinal inflammation and inflammation-associated cancer.

Item Type: Article
Additional Information: Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
Uncontrolled Keywords: caspases,humans,immunity, cellular,inflammatory bowel diseases
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User: Pure Connector
Date Deposited: 07 Jul 2014 15:02
Last Modified: 25 Jul 2018 09:46
URI: https://ueaeprints.uea.ac.uk/id/eprint/48983
DOI: 10.1053/j.gastro.2012.11.035

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