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Anti‐inflammatory functions of the “apoptotic” caspases
Author(s) -
Wallach David,
Kang TaeBong,
Rajput Akhil,
Kim JinChul,
Bogdanov Konstantin,
Yang SeungHoon,
Kovalenko Andrew
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2010.05742.x
Subject(s) - caspase , inflammation , proinflammatory cytokine , microbiology and biotechnology , apoptosis , programmed cell death , epidermis (zoology) , chemistry , biology , immunology , biochemistry , anatomy
The two main known functions of the caspases act antagonistically in regulating inflammation. “Inflammatory” caspases trigger inflammation by catalyzing the processing of IL‐1β precursors and other proinflammatory cytokines. In contrast, “apoptotic” caspases safeguard against the triggering of inflammation by imposing a cell‐death form that withholds release of alarmins by dying cells and dictates generation of anti‐inflammatory mediators. These antagonizing functions are exerted by evolution‐related mechanisms. Studies of the function of caspase‐8, an enzyme‐mediating apoptotic cell‐death induction in response to TNF‐family ligands, reveal that it blocks inflammation in additional ways. One way is by restricting activation of the RIG‐I complex by foreign ribonucleic acid. Chronic skin inflammation in mice with caspase‐8–deficient epidermis is associated with constitutive activation of the RIG‐I complex in keratinocytes. This activation is apparently prompted by nucleic acids released from epidermal cells that disintegrate during cornification, and becomes chronic because it is not restricted by caspase‐8.