The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury
Open accessAbstract
The inhibitor of NF-kappaB (I-kappaB) kinase (IKK) complex consists of 3 subunits, IKK1, IKK2, and NF-kappaB essential modulator (NEMO), and is involved in the activation of NF-kappaB by various stimuli. IKK2 or NEMO constitutive knockout mice die during embryogenesis as a result of massive hepatic apoptosis. Therefore, we examined the role of IKK2 in TNF-induced apoptosis and ischemia/reperfusion (I/R) injury in the liver by using conditional knockout mice. Hepatocyte-specific ablation of IKK2 did not lead to impaired activation of NF-kappaB or increased apoptosis after TNF-alpha stimulation whereas conditional NEMO knockout resulted in complete block of NF-kappaB activation and massive hepatocyte apoptosis. In a model of partial hepatic I/R injury, mice lacking IKK2 in hepatocytes displayed significantly reduced liver necrosis and inflammation than wild-type mice. AS602868, a novel chemical inhibitor of IKK2, protected mice from liver injury due to I/R without sensitizing them toward TNF-induced apoptosis and could therefore emerge as a new pharmacological therapy for liver resection, hemorrhagic shock, or transplantation surgery.
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Cites
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Severe liver degeneration and lack of NF-κ B activation in NEMO/IKKγ-deficient mice
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IKKβ Is Required for Prevention of Apoptosis Mediated by Cell-Bound but Not by Circulating TNFα
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Cited by
NF-κB in the liver—linking injury, fibrosis and hepatocellular carcinoma
Luedde, T., & Schwabe, R. F. (2011) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.213 · Cited by 1,345
Self-citationNF-κB and STAT3 – key players in liver inflammation and cancer
He, G., & Karin, M. (2011) · Cell Research · doi:10.1038/cr.2010.183 · Cited by 1,197
Mitochondrial Glutathione, a Key Survival Antioxidant
Marí, M., Morales, A., Colell, A., García-Ruiz, C., & Fernández-Checa, J. C. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2695 · Cited by 980
Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance
Luedde, T., Kaplowitz, N., & Schwabe, R. F. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.07.018 · Cited by 759
Self-citationMechanisms of Liver Injury. I. TNF-α-induced liver injury: role of IKK, JNK, and ROS pathways
Schwabe, R. F., & Brenner, D. A. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00422.2005 · Cited by 685
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Metadata
- Authors
- Luedde, T., Assmus, U., Wüstefeld, T., Meyer zu Vilsendorf, A., Roskams, T., Schmidt-Supprian, M., Rajewsky, K., Brenner, D. A., Manns, M. P., Pasparakis, M., & Trautwein, C.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-03-17
- Volume
- 115
- Issue
- 4
- Pages
- 849-859
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2109855059
- Cited by
- 178
- References
- 7
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury. https://app.cochat.ai/papers/10.1172/jci200523493
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- Luedde, T., Assmus, U., Wüstefeld, T., Meyer zu Vilsendorf, A., Roskams, T., Schmidt-Supprian, M., Rajewsky, K., Brenner, D. A., Manns, M. P., Pasparakis, M., & Trautwein, C. (2005). Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury. Journal of Clinical Investigation. https://doi.org/10.1172/jci200523493
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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