Role of caspase-8 in hepatocyte response to infection and injury in mice.
Caspase-8 has been implicated in signaling for apoptotic cell death and for certain nonapoptotic functions. However, knowledge of actual physiological or pathophysiological processes to which this enzyme contributes is lacking. Using a mouse model and employing the conditional knockout approach to delete the caspase-8 gene specifically in the liver, we found that caspase-8 deficiency in hepatocytes facilitates infection of the liver by Listeria monocytogenes, attenuates the hepatocyte proliferation wave during the first 48 hours after partial hepatectomy and, depending on the genetic background of the mice, prompts a chronic inflammatory response to the hepatectomy, as a result of which the proliferation of hepatocytes, although initially suppressed, might later be persistently enhanced, resulting in significant hepatomegaly.


CONCLUSIONS
These findings indicate that caspase-8 participates in regulation of the cellular response to infection and injury and that it does so by affecting various cellular functions, including cell death, cell proliferation, and induction of inflammation.
Ben Moshe
Tehila
T
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
Barash
Hila
H
Kang
Tae-Bong
TB
Kim
Jin-Chul
JC
Kovalenko
Andrew
A
Gross
Eitan
E
Schuchmann
Marcus
M
Abramovitch
Rinat
R
Galun
Eithan
E
Wallach
David
D
D000818:Animals; D053181:Caspase 8 / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D049109:Cell Proliferation; D022781:Hepatocytes / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology; D008088:Listeriosis / Q000503:physiopathology*; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout
D053181:Caspase 8