Anti-inflammatory functions of the "apoptotic" caspases.
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.
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel. d.wallach@weizmann.ac.il
David
D
Wallach
Tae-Bong
TB
Kang
Akhil
A
Rajput
Jin-Chul
JC
Kim
Konstantin
K
Bogdanov
Seung-Hoon
SH
Yang
Andrew
A
Kovalenko
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D015398:Signal Transduction
D020169:Caspases