Ghent University Academic Bibliography

Advanced

RIPK1 protects from TNF-alpha-mediated liver damage during hepatitis

Aveline Filliol, Claire Piquet-Pellorce, Jacques Le Seyec, Muhammad Farooq, Valentine Genet, Catherine Lucas-Clerc, John Bertin, Peter J. Gough, Marie-Therese Dimanche-Boitrel, Peter Vandenabeele UGent, et al. (2016) CELL DEATH & DISEASE. 7.
abstract
Cell death of hepatocytes is a prominent characteristic in the pathogenesis of liver disease, while hepatolysis is a starting point of inflammation in hepatitis and loss of hepatic function. However, the precise molecular mechanisms of hepatocyte cell death, the role of the cytokines of hepatic microenvironment and the involvement of intracellular kinases, remain unclear. Tumor necrosis factor alpha (TNF-alpha) is a key cytokine involved in cell death or survival pathways and the role of RIPK1 has been associated to the TNF-alpha-dependent signaling pathway. We took advantage of two different deficient mouse lines, the RIPK1 kinase dead knock-in mice (Ripk1K45A) and the conditional knockout mice lacking RIPK1 only in liver parenchymal cells (Ripk1LPC-KO), to characterize the role of RIPK1 and TNF-alpha in hepatitis induced by concanavalin A (ConA). Our results show that RIPK1 is dispensable for liver homeostasis under steady-state conditions but in contrast, RIPK1 kinase activity contributes to caspase-independent cell death induction following ConA injection and RIPK1 also serves as a scaffold, protecting hepatocytes from massive apoptotic cell death in this model. In the Ripk1LPC-KO mice challenged with ConA, TNF-alpha triggers apoptosis, responsible for the observed severe hepatitis. Mechanism potentially involves both TNF-independent canonical NF-kappa B activation, as well as TNF-dependent, but canonical NF-kappa B-independent mechanisms. In conclusion, our results suggest that RIPK1 kinase activity is a pertinent therapeutic target to protect liver against excessive cell death in liver diseases.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
TUMOR-NECROSIS-FACTOR, NF-KAPPA-B, MURINE ACETAMINOPHEN TOXICITY, , A-INDUCED HEPATITIS, HEPATOCELLULAR-CARCINOMA, IL-33 EXPRESSION, , IN-VIVO, MOUSE HEPATOCYTES, INDUCED APOPTOSIS, KINASE-ACTIVITY
journal title
CELL DEATH & DISEASE
Cell Death Dis.
volume
7
article number
e2462
pages
13 pages
publisher
Nature Publishing Group
place of publication
London
Web of Science type
J
Web of Science id
000391815400026
ISSN
2041-4889
DOI
10.1038/cddis.2016.362
language
English
UGent publication?
yes
classification
U
copyright statement
Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
id
8510060
handle
http://hdl.handle.net/1854/LU-8510060
date created
2017-02-17 16:11:20
date last changed
2017-02-17 16:11:24
@article{8510060,
  abstract     = {Cell death of hepatocytes is a prominent characteristic in the pathogenesis of liver disease, while hepatolysis is a starting point of inflammation in hepatitis and loss of hepatic function. However, the precise molecular mechanisms of hepatocyte cell death, the role of the cytokines of hepatic microenvironment and the involvement of intracellular kinases, remain unclear. Tumor necrosis factor alpha (TNF-alpha) is a key cytokine involved in cell death or survival pathways and the role of RIPK1 has been associated to the TNF-alpha-dependent signaling pathway. We took advantage of two different deficient mouse lines, the RIPK1 kinase dead knock-in mice (Ripk1K45A) and the conditional knockout mice lacking RIPK1 only in liver parenchymal cells (Ripk1LPC-KO), to characterize the role of RIPK1 and TNF-alpha in hepatitis induced by concanavalin A (ConA). Our results show that RIPK1 is dispensable for liver homeostasis under steady-state conditions but in contrast, RIPK1 kinase activity contributes to caspase-independent cell death induction following ConA injection and RIPK1 also serves as a scaffold, protecting hepatocytes from massive apoptotic cell death in this model. In the Ripk1LPC-KO mice challenged with ConA, TNF-alpha triggers apoptosis, responsible for the observed severe hepatitis. Mechanism potentially involves both TNF-independent canonical NF-kappa B activation, as well as TNF-dependent, but canonical NF-kappa B-independent mechanisms. In conclusion, our results suggest that RIPK1 kinase activity is a pertinent therapeutic target to protect liver against excessive cell death in liver diseases.},
  articleno    = {e2462},
  author       = {Filliol, Aveline and Piquet-Pellorce, Claire and Le Seyec, Jacques and Farooq, Muhammad and Genet, Valentine and Lucas-Clerc, Catherine and Bertin, John and Gough, Peter J. and Dimanche-Boitrel, Marie-Therese and Vandenabeele, Peter and Bertrand, Mathieu and Samson, Michel},
  issn         = {2041-4889},
  journal      = {CELL DEATH \& DISEASE},
  keyword      = {TUMOR-NECROSIS-FACTOR,NF-KAPPA-B,MURINE ACETAMINOPHEN TOXICITY,,A-INDUCED HEPATITIS,HEPATOCELLULAR-CARCINOMA,IL-33 EXPRESSION,,IN-VIVO,MOUSE HEPATOCYTES,INDUCED APOPTOSIS,KINASE-ACTIVITY},
  language     = {eng},
  pages        = {13},
  publisher    = {Nature Publishing Group},
  title        = {RIPK1 protects from TNF-alpha-mediated liver damage during hepatitis},
  url          = {http://dx.doi.org/10.1038/cddis.2016.362},
  volume       = {7},
  year         = {2016},
}

Chicago
Filliol, Aveline, Claire Piquet-Pellorce, Jacques Le Seyec, Muhammad Farooq, Valentine Genet, Catherine Lucas-Clerc, John Bertin, et al. 2016. “RIPK1 Protects from TNF-alpha-mediated Liver Damage During Hepatitis.” Cell Death & Disease 7.
APA
Filliol, A., Piquet-Pellorce, C., Le Seyec, J., Farooq, M., Genet, V., Lucas-Clerc, C., Bertin, J., et al. (2016). RIPK1 protects from TNF-alpha-mediated liver damage during hepatitis. CELL DEATH & DISEASE, 7.
Vancouver
1.
Filliol A, Piquet-Pellorce C, Le Seyec J, Farooq M, Genet V, Lucas-Clerc C, et al. RIPK1 protects from TNF-alpha-mediated liver damage during hepatitis. CELL DEATH & DISEASE. London: Nature Publishing Group; 2016;7.
MLA
Filliol, Aveline, Claire Piquet-Pellorce, Jacques Le Seyec, et al. “RIPK1 Protects from TNF-alpha-mediated Liver Damage During Hepatitis.” CELL DEATH & DISEASE 7 (2016): n. pag. Print.