Inflammatory caspases: key regulators of inflammation and cell death

• Published in: Biological chemistry Vol. 396; no. 3; pp. 193 - 203
• Main Authors: Fernández, Daniel Jiménez, Lamkanfi, Mohamed
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 01.03.2015
• Subjects: Animals; caspase; Caspases - metabolism; Cell Death; Cytokines - metabolism; Enzyme Activation; Humans; infection; inflammasome; Inflammasomes; inflammation; Inflammation - enzymology; Inflammation - pathology; NOD-like receptor; pyroptosis
• ISSN: 1431-6730; 1437-4315; 1437-4315
• DOI: 10.1515/hsz-2014-0253

The innate immune system represents the first line of defence against infectious agents, and co-ordinates cellular and molecular mechanisms that result in effective inflammatory and anti-microbial responses against pathogens. Infection and cellular stress trigger assembly of canonical and noncanonical inflammasome complexes that activate the inflammatory caspases-1 and -11, respectively. These inflammatory caspases play key roles in innate immune responses by inducing pyroptosis to halt intracellular replication of pathogens, and by engaging the extracellular release of pro-inflammatory cytokines and danger signals. In addition, the inflammatory caspases-4, -5 and -11 were recently shown to directly bind microbial components. Although the immune roles of caspase-12 are debated, it was proposed to dampen inflammatory responses by interfering with caspase-1 activation and other innate immune pathways. Here, we recapitulate the reported roles of inflammatory caspases with an emphasis on recent insights into their biological functions.