Journal article
Hepatic expression of the tumor necrosis factor family member lymphotoxin-beta is regulated by interleukin (IL)-6 and IL-1beta: transcriptional control mechanisms in oval cells and hepatoma cell lines
Liver International, Vol.25(3), pp.633-646
2005
Abstract
Background: Lymphotoxin-β (LT-β) plays an important role in inflammation and its promoter contains a functional nuclear factor-κB (NF-κB) element, rendering it a likely target of pro-inflammatory cytokines. Inflammatory cytokines play a central role in liver regeneration resulting from acute or chronic liver injury, with interleukin (IL)-6 signaling essential for liver regeneration induced by partial hepatectomy. In hepatic oval cells observed following chronic liver injury, LT-β levels are upregulated, suggesting a link between LT-β and liver regeneration.
Results: The expression of LT-β in hepatic oval cell and hepatocellular carcinoma cell lines was further investigated, along with its responsiveness to IL-6 and IL-1β. Key regulatory cis-acting elements of the LT-β promoter that mediate IL-6 responsiveness (Sp/BKLF, Ets, NF-κB and Egr-1/Sp1) and IL-1β responsiveness (NF-κB and Ets) of hepatic LT-β expression were identified. The novel binding of basic Kruppel-like factor (BKLF) proteins to an apparent composite Sp/BKLF site of the LT-β promoter was shown to mediate IL-6 responsiveness. Binding of NF-κB p65/p50 heterodimers and Ets-related transcription factors to their respective sites mediates responsiveness to IL-1β.
Conclusion: The identification of IL-6 and IL-1β as activators of LT-β supports their involvement in LT-β signaling in liver regeneration associated with chronic liver damage.
Details
- Title
- Hepatic expression of the tumor necrosis factor family member lymphotoxin-beta is regulated by interleukin (IL)-6 and IL-1beta: transcriptional control mechanisms in oval cells and hepatoma cell lines
- Authors/Creators
- L.S. Subrata (Author/Creator) - The University of Western AustraliaK.N. Lowes (Author/Creator) - The Western Australian Institute for Medical Research, UWA Centre for Medical Research, andJ.K. Olynyk (Author/Creator) - The Western Australian Institute for Medical Research, UWA Centre for Medical Research, andG.C.T. Yeoh (Author/Creator) - The Western Australian Institute for Medical Research, UWA Centre for Medical Research, andE.A. Quail (Author/Creator) - Biochemistry and Molecular Biology, School of Biomedical and Chemical Sciences,L.J. Abraham (Author/Creator) - The Western Australian Institute for Medical Research, UWA Centre for Medical Research, and
- Publication Details
- Liver International, Vol.25(3), pp.633-646
- Publisher
- Wiley-Blackwell
- Identifiers
- 991005540203407891
- Copyright
- 2005 Blackwell Munksgaard
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 1 Clinical & Life Sciences
- 1.102 Stem Cell Research
- 1.102.1150 Hepatocyte Growth Factor
- Web Of Science research areas
- Gastroenterology & Hepatology
- ESI research areas
- Clinical Medicine