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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2257-2265
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1842
Issue number11
DOIs
StatePublished - Nov 1 2014

Fingerprint

Inflammation
Liver
Hepatocytes
Lipids
High Fat Diet
Transcriptional Activation
Copper
Homeostasis
Transcription Factors
Cholesterol
Cytokines
Diet
Non-alcoholic Fatty Liver Disease
Proteins

Keywords

  • COMMD1
  • Inflammation
  • Macrophages
  • NAFLD
  • NF-κB inhibitor

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

Bartuzi, P., Wijshake, T., Dekker, D. C., Fedoseienko, A., Kloosterhuis, N. J., Youssef, S. A., ... van de Sluis, B. (2014). A cell-type-specific role for murine Commd1 in liver inflammation. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1842(11), 2257-2265. https://doi.org/10.1016/j.bbadis.2014.06.035

A cell-type-specific role for murine Commd1 in liver inflammation. / Bartuzi, Paulina; Wijshake, Tobias; Dekker, Daphne C.; Fedoseienko, Alina; Kloosterhuis, Niels J.; Youssef, Sameh A.; Li, Haiying; Shiri-Sverdlov, Ronit; Kuivenhoven, Jan Albert; de Bruin, Alain; Burstein, Ezra; Hofker, Marten H.; van de Sluis, Bart.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1842, No. 11, 01.11.2014, p. 2257-2265.

Research output: Contribution to journalArticle

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 2014, 'A cell-type-specific role for murine Commd1 in liver inflammation', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1842, no. 11, pp. 2257-2265. https://doi.org/10.1016/j.bbadis.2014.06.035
Bartuzi P, Wijshake T, Dekker DC, Fedoseienko A, Kloosterhuis NJ, Youssef SA et al. A cell-type-specific role for murine Commd1 in liver inflammation. Biochimica et Biophysica Acta - Molecular Basis of Disease. 2014 Nov 1;1842(11):2257-2265. https://doi.org/10.1016/j.bbadis.2014.06.035
Bartuzi, Paulina ; Wijshake, Tobias ; Dekker, Daphne C. ; Fedoseienko, Alina ; Kloosterhuis, Niels J. ; Youssef, Sameh A. ; Li, Haiying ; Shiri-Sverdlov, Ronit ; Kuivenhoven, Jan Albert ; de Bruin, Alain ; Burstein, Ezra ; Hofker, Marten H. ; van de Sluis, Bart. / A cell-type-specific role for murine Commd1 in liver inflammation. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2014 ; Vol. 1842, No. 11. pp. 2257-2265.
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