| First Author | Bartuzi P | Year | 2014 |
| Journal | Biochim Biophys Acta | Volume | 1842 |
| Issue | 11 | Pages | 2257-65 |
| PubMed ID | 25072958 | Mgi Jnum | J:218475 |
| Mgi Id | MGI:5617659 | Doi | 10.1016/j.bbadis.2014.06.035 |
| Citation | Bartuzi P, et al. (2014) A cell-type-specific role for murine Commd1 in liver inflammation. Biochim Biophys Acta 1842(11):2257-65 |
| abstractText | The transcription factor NF-kappaB 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-kappaB activation may protect tissues from stress, a prolonged NF-kappaB 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-kappaB 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-kappaB 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. |
