RGD Reference Report - Regulated expression of the apolipoprotein E/C-I/C-IV/C-II gene cluster in murine and human macrophages. A critical role for nuclear liver X receptors alpha and beta. - Rat Genome Database

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Regulated expression of the apolipoprotein E/C-I/C-IV/C-II gene cluster in murine and human macrophages. A critical role for nuclear liver X receptors alpha and beta.

Authors: Mak, PA  Laffitte, BA  Desrumaux, C  Joseph, SB  Curtiss, LK  Mangelsdorf, DJ  Tontonoz, P  Edwards, PA 
Citation: Mak PA, etal., J Biol Chem 2002 Aug 30;277(35):31900-8. Epub 2002 May 24.
RGD ID: 1358407
Pubmed: PMID:12032151   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M202993200   (Journal Full-text)

Lipid-loaded macrophage "foam cells" accumulate in the subendothelial space during the development of fatty streaks and atherosclerotic lesions. To better understand the consequences of such lipid loading, murine peritoneal macrophages were isolated and incubated with ligands for two nuclear receptors, liver X receptor (LXR) and retinoic acid receptor (RXR). Analysis of the expressed mRNAs using microarray technology led to the identification of four highly induced genes that encode apolipoproteins E, C-I, C-IV, and C-II. Northern blot analysis confirmed that the mRNA levels of these four genes were induced 2-14-fold in response to natural or synthetic ligands for LXR and/or RXR. The induction of all four mRNAs was greatly attenuated in peritoneal macrophages derived from LXRalpha/beta null mice. The two LXR response elements located within the multienhancers ME.1 and ME.2 were shown to be essential for the induction of apoC-II promoter-reporter genes by ligands for LXR and/or RXR. Finally, immunohistochemical studies demonstrate that apoC-II protein co-localizes with macrophages within murine arterial lesions. Taken together, these studies demonstrate that activated LXR induces the expression of the apoE/C-I/C-IV/C-II gene cluster in both human and murine macrophages. These results suggest an alternative mechanism by which lipids are removed from macrophage foam cells.

Objects referenced in this article
Gene Apoc1 apolipoprotein C-I Mus musculus
Gene Apoc2 apolipoprotein C2 Mus musculus
Gene Apoc2 apolipoprotein C2 Rattus norvegicus

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