The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Interleukin-10 Signaling Blocks Inhibitor of κB Kinase Activity and Nuclear Factor κB DNA Binding
Open accessAbstract
The transcription factor nuclear factor kappaB (NF-kappaB) coordinates the activation of numerous genes in response to pathogens and proinflammatory cytokines and is, therefore, pivotal in the development of acute and chronic inflammatory diseases. In its inactive state, NF-kappaB is constitutively present in the cytoplasm as a p50-p65 heterodimer bound to its inhibitory protein IkappaB. Proinflammatory cytokines, such as tumor necrosis factor (TNF), activate NF-kappaB by stimulating the activity of the IkappaB kinases (IKKs) which phosphorylate IkappaBalpha on serine residues 32 and 36, targeting it for rapid degradation by the 26 S proteasome. This enables the release and nuclear translocation of the NF-kappaB complex and activation of gene transcription. Interleukin-10 (IL-10) is a pleiotropic cytokine that controls inflammatory processes by suppressing the production of proinflammatory cytokines which are known to be transcriptionally controlled by NF-kappaB. Conflicting data exists on the effects of IL-10 on TNF- and LPS-induced NF-kappaB activity in human monocytes and the molecular mechanisms involved have not been elucidated. In this study, we show that IL-10 functions to block NF-kappaB activity at two levels: 1) through the suppression of IKK activity and 2) through the inhibition of NF-kappaB DNA binding activity. This is the first evidence of an anti-inflammatory protein inhibiting IKK activity and demonstrates that IKK is a logical target for blocking inflammatory diseases.
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Cites
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Cited by
Interleukin-10 and the Interleukin-10 Receptor
Moore, K. W., de Waal Malefyt, R., Coffman, R. L., & O'Garra, A. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.683 · Cited by 6,737
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29881 · Cited by 4,664
NF-κB: a key role in inflammatory diseases
Tak, P. P., & Firestein, G. S. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11830 · Cited by 3,918
A cytokine-mediated link between innate immunity, inflammation, and cancer
Lin, W.-W., & Karin, M. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31537 · Cited by 1,940
Chronic inflammation and cytokines in the tumor microenvironment
Landskron, G., De la Fuente, M., Thuwajit, P., Thuwajit, C., & Hermoso, M. A. (2014) · Journal of Immunology Research · doi:10.1155/2014/149185 · Cited by 1,765
Metadata
- Authors
- Schottelius, A. J. G., Mayo, M. W., Sartor, R. B., & Baldwin, A. S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-11
- Volume
- 274
- Issue
- 45
- Pages
- 31868-31874
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2012194278
- Cited by
- 532
- References
- 55
- FWCI
- 7.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Schottelius, A. J. G., Mayo, M. W., Sartor, R. B., & Baldwin, A. S. (1999). Interleukin-10 Signaling Blocks Inhibitor of κB Kinase Activity and Nuclear Factor κB DNA Binding. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.45.31868
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