A perspective on mammalian caspases as positive and negative regulators of inflammation.
Item Type:Journal Article
Citation:Martin SJ, Henry CM, Cullen SP, A perspective on mammalian caspases as positive and negative regulators of inflammation., Molecular cell, 46, 4, 2012, 387-397
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Members of the caspase family of cysteine proteases coordinate the morphological and biochemical events that typify apoptosis. However, neutralization of caspase activity in mammals fails to block death in response to most proapoptotic stimuli. This is because many cell death triggers provoke mitochondrial dysfunction upstream of caspase activation as a consequence of BAX/BAK channel opening. Although genetic or phar- macological inactivation of caspases fails to block cell death in most instances, it does convert the pheno- type from apoptosis to necrosis. This has important implications for how the immune system responds to such cells, as necrotic cells provoke inflammation whereas apoptotic cells typically do not. Here, we propose an alternative perspective on apoptosis-associated caspase function by suggesting that these proteases are activated, not to kill, but to extinguish the proinflammatory properties of dying cells. This perspective unifies the mammalian caspase family as either positive or negative regulators of inflammation.
Science Foundation Ireland (SFI)
Author: MARTIN, SEAMUS
Type of material:Journal Article
Series/Report no:Molecular cell
Availability:Full text available
Subject (TCD):Immunology, Inflammation & Infection