The DOI matches its Crossref record; 64 of the 65 references it cites were found in a registry or an index.
IKKβ Is Required for Prevention of Apoptosis Mediated by Cell-Bound but Not by Circulating TNFα
Open accessAbstract
IkappaB kinase beta (IKKbeta) is required for NF-kappaB activation and suppression of TNFalpha-mediated liver apoptosis. To investigate how IKKbeta suppresses apoptosis, we generated hepatocyte-specific Ikkbeta knockout mice, Ikkbeta(Deltahep), which exhibit little residual NF- kappaB activity but are healthy with normal liver function. Unexpectedly, Ikkbeta(Deltahep) mice are slightly more sensitive than controls to LPS-induced liver apoptosis but are highly susceptible to liver destruction following concanavalin A (ConA)-induced T cell activation. Unlike LPS, a potent inducer of circulating TNFalpha, ConA exerts cytotoxic effects through cell-bound TNFalpha, which activates type 1 and 2 TNF receptors (TNFR). While TNFR2 does not contribute to NF-kappaB activation, it is important for ConA-induced JNK activation, which is augmented by the absence of IKKbeta. Using JNK-deficient mice we show that JNK is required for ConA-induced liver damage. Thus, the antiapoptotic function of IKKbeta, which is most critical in situations that involve cell-bound TNFalpha, is mediated partially through attenuation of JNK activity.
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In the citing paper
“Maeda et al. established that when NFκB function is selectively inactivated in hepatocytes, IL-6 mRNA production is severely muted in whole livers obtained from mice at 4 h after injection of LPS [6].”
From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [6]
In the citing paper
“and as NFκB can act upstream of IL-6 to control synthesis [6], [7]”
From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [6]
In the citing paper
“IL-6 mRNA production is known to subsequently occur under the transcriptional control of NFκB [6], [7].”
From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [6]
In the citing paper
“As the time frame in which the observed the changes in IL-6 was rapid, and the induced NFκB defect was hepatocyte-specific, these experiments suggested to us that hepatocytes, in addition to immune cells, might also serve as a direct source of IL-6 during an acute phase reaction, i.e. the hepatic response might also have an autocrine component.”
From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [6]
In the citing paper
“Our p65 data supports the finding that there was a paucity of nuclear NFκB reported by Maeda et al when nuclei from hepatocyte-specific NFκB knockouts, versus their control counterparts, were subjected to EMSA at 1 h following LPS injection [6]”
From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [6]
In the citing paper
“the other two investigations were performed using gel shift analyses without subsequent supershift confirmation to ensure that both subunits of prototypical NFκB were in the DNA-binding complex.”
From Synthesis of IL-6 by Hepatocytes Is a Normal Response to Common Hepatic Stimuli (2014) · cites this paper as [6]
Citations
Cites
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A cytokine-responsive IκB kinase that activates the transcription factor NF-κB
DiDonato, J. A., Hayakawa, M., Rothwarf, D. M., Zandi, E., & Karin, M. (1997) · Nature · doi:10.1038/41493 · Cited by 2,125
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Self-citationEmbryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB
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Research works printed but not linked: 1
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Signal integration by JNK and p38 MAPK pathways in cancer development
Wagner, E. F., & Nebreda, Á. R. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2694 · Cited by 2,635
The two NF-κB activation pathways and their role in innate and adaptive immunity
Bonizzi, G., & Karin, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.03.008 · Cited by 2,535
Self-citationIKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer
Greten, F. R., Eckmann, L., Greten, T. F., Park, J. M., Li, Z.-W., Egan, L. J., Kagnoff, M. F., & Karin, M. (2004) · Cell · doi:10.1016/j.cell.2004.07.013 · Cited by 2,433
Self-citationNF-κB functions as a tumour promoter in inflammation-associated cancer
Pikarsky, E., Porat, R. M., Stein, I., Abramovitch, R., Amit, S., Kasem, S., Gutkovich-Pyest, E., Urieli-Shoval, S., Galun, E., & Ben‐Neriah, Y. (2004) · Nature · doi:10.1038/nature02924 · Cited by 2,423
Kamata, H., Honda, S.-I., Maeda, S., Chang, L., Hirata, H., & Karin, M. (2005) · Cell · doi:10.1016/j.cell.2004.12.041 · Cited by 1,792
Self-citation
Metadata
- Authors
- Maeda, S., Chang, L., Li, Z.-W., Luo, J.-L., Leffert, H., & Karin, M.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Karin, Michael
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 19
- Issue
- 5
- Pages
- 725-737
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2057942179
- Cited by
- 286
- References
- 65
- Citations by year
- 2024: 3 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 4 · 2018: 6 · 2017: 11 · 2016: 12 · 2015: 9 · 2014: 9 · 2013: 12 · 2012: 16
- FWCI
- 8.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI 43477)
- National Institute of Environmental Health Sciences (P42ES010337, ES10337, ES 06376, R01ES006376)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- IκB kinase β, NF-κB activation, apoptosis, TNF receptor 2, JNK, concanavalin A, T cell activation, liver injury, hepatocyte-specific knockout mice, antiapoptotic function
- MeSH terms
- Animals, Concanavalin A, Lipopolysaccharides, Liver, Mice, Inbred C57BL, T-Lymphocytes, Tumor Necrosis Factor-alpha, Antigens, CD, Apoptosis, Protein Serine-Threonine Kinases, Receptors, Tumor Necrosis Factor, Mice, Knockout, Mitogen-Activated Protein Kinases, Receptors, Tumor Necrosis Factor, Type II, JNK Mitogen-Activated Protein Kinases, Mice, I-kappa B Kinase
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