Macrophage regulation

Hypercholesterolemia, a risk factor linked to chronic inflammation and atherosclerosis, is associated with an accumulation of macrophage foam cells in arterial lesions. In Cell, Spann et al. report the surprising finding that excess free cholesterol suppresses the expression of genes encoding proinflammatory molecules in mouse and human macrophages. Quantitative transcriptional and lipidomic analyses shows that cholesterol metabolism is regulated by desmosterol, an agonist of LXR (a member of the nuclear receptor family of transcription factors). Desmosterol concentrations increase during hypercholesterolemia. High concentrations of desmosterol inhibit the expression of Il1b, Nos2, Cxcl9 and Cxcl10 by activating LXR-mediated mechanisms that suppress the histone acetylation necessary for gene expression. These findings challenge the conventional assumption that foam cells are the source of inflammatory mediators in atherosclerosis and prompt further investigation to determine how inflammation arises.

Cell 151, 138–152 (2012)

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Dempsey, L. Macrophage regulation. Nat Immunol 13, 1143 (2012). https://doi.org/10.1038/ni.2486

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