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Bartuzi P, Wijshake T, Dekker DC, et al. A cell-type-specific role for murine Commd1 in liver inflammation. Biochim Biophys Acta. 2014;1842(11):2257-65doi: 10.1016/j.bbadis.2014.06.035.
Bartuzi, P., Wijshake, T., Dekker, D. C., Fedoseienko, A., Kloosterhuis, N. J., Youssef, S. A., Li, H., Shiri-Sverdlov, R., Kuivenhoven, J. A., de Bruin, A., Burstein, E., Hofker, M. H., & van de Sluis, B. (2014). A cell-type-specific role for murine Commd1 in liver inflammation. Biochimica et biophysica acta, 1842(11), 2257-65. https://doi.org/10.1016/j.bbadis.2014.06.035
Bartuzi, Paulina, et al. "A cell-type-specific role for murine Commd1 in liver inflammation." Biochimica et biophysica acta vol. 1842,11 (2014): 2257-65. doi: https://doi.org/10.1016/j.bbadis.2014.06.035
Bartuzi P, Wijshake T, Dekker DC, Fedoseienko A, Kloosterhuis NJ, Youssef SA, Li H, Shiri-Sverdlov R, Kuivenhoven JA, de Bruin A, Burstein E, Hofker MH, van de Sluis B. A cell-type-specific role for murine Commd1 in liver inflammation. Biochim Biophys Acta. 2014 Nov;1842(11):2257-65. doi: 10.1016/j.bbadis.2014.06.035. Epub 2014 Jul 27. PMID: 25072958; PMCID: PMC4188638.
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Biochim Biophys Acta. 2014 Nov;1842(11):2257-65. doi: 10.1016/j.bbadis.2014.06.035. Epub 2014 Jul 27.

A cell-type-specific role for murine Commd1 in liver inflammation.

Biochimica et biophysica acta

Paulina Bartuzi, Tobias Wijshake, Daphne C Dekker, Alina Fedoseienko, Niels J Kloosterhuis, Sameh A Youssef, Haiying Li, Ronit Shiri-Sverdlov, Jan-Albert Kuivenhoven, Alain de Bruin, Ezra Burstein, Marten H Hofker, Bart van de Sluis

Affiliations

  1. University of Groningen, University Medical Center Groningen, Department of Pediatrics, Molecular Genetics Section, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
  2. Dutch Molecular Pathology Center, Department of Pathology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, De Uithof, 3584 CL Utrecht, The Netherlands.
  3. University of Texas Southwestern Medical Center, Departments of Internal Medicine and Molecular Biology, Dallas, TX 75390-9151, USA.
  4. Department of Molecular Genetics, Maastricht University, 6202 AZ Maastricht, The Netherlands.
  5. University of Groningen, University Medical Center Groningen, Department of Pediatrics, Molecular Genetics Section, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. Electronic address: [email protected].

PMID: 25072958 PMCID: PMC4188638 DOI: 10.1016/j.bbadis.2014.06.035

Abstract

The transcription factor NF-κB plays a critical role in the inflammatory response and it has been implicated in various diseases, including non-alcoholic fatty liver disease (NAFLD). Although transient NF-κB activation may protect tissues from stress, a prolonged NF-κB activation can have a detrimental effect on tissue homeostasis and therefore accurate termination is crucial. Copper Metabolism MURR1 Domain-containing 1 (COMMD1), a protein with functions in multiple pathways, has been shown to suppress NF-κB activity. However, its action in controlling liver inflammation has not yet been investigated. To determine the cell-type-specific contribution of Commd1 to liver inflammation, we used hepatocyte and myeloid-specific Commd1-deficient mice. We also used a mouse model of NAFLD to study low-grade chronic liver inflammation: we fed the mice a high fat, high cholesterol (HFC) diet, which results in hepatic lipid accumulation accompanied by liver inflammation. Depletion of hepatocyte Commd1 resulted in elevated levels of the NF-κB transactivation subunit p65 (RelA) but, surprisingly, the level of liver inflammation was not aggravated. In contrast, deficiency of myeloid Commd1 exacerbated diet-induced liver inflammation. Unexpectedly we observed that hepatic and myeloid Commd1 deficiency in the mice both augmented hepatic lipid accumulation. The elevated levels of proinflammatory cytokines in myeloid Commd1-deficient mice might be responsible for the increased level of steatosis. This increase was not seen in hepatocyte Commd1-deficient mice, in which increased lipid accumulation appeared to be independent of inflammation. Our mouse models demonstrate a cell-type-specific role for Commd1 in suppressing liver inflammation and in the progression of NAFLD.

Copyright © 2014 Elsevier B.V. All rights reserved.

Keywords: COMMD1; Inflammation; Macrophages; NAFLD; NF-κB inhibitor

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