Department of Medicine, Division of Infectious Diseases and Immunology
Biochemistry | Cellular and Molecular Physiology | Lipids
During screening of genes upregulated by lipopolysaccharide (LPS; endotoxin) treatment of bone marrow-derived mouse macrophages, it was unexpectedly found that cholesterol 25-hydroxylase (Ch25h) was strongly upregulated. Treatment of macrophages with 10 ng/ml of LPS for 2 h resulted in a 35-fold increase in the expression of Ch25h. In contrast, LPS treatment did not increase the expression of Cyp27a1 or Cyp7b1. The increased Ch25h expression was found to be independent of Myeloid differentiation protein 88 signaling but dependent on Toll-like receptor 4 signaling. LPS treatment of macrophages caused a 6- to 7-fold increase in cellular 25-hydroxycholesterol concentration. When macrophages were treated with increasing concentrations of 25-hydroxycholesterol, a dose-dependent release of CCL5 into the culture medium was observed. Intravenous injection of LPS in eight healthy volunteers resulted in an increase in plasma 25-hydroxycholesterol concentration. The possibility is discussed that 25-hydroxycholesterol may have a role in the inflammatory response, in addition to its more established role in the regulation of cholesterol homeostasis.
25-hydroxycholesterol, oxysterols, endotoxin, inflammation, sepsis, macrophages
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Copyright © 2009 by the American Society for Biochemistry and Molecular Biology, Inc. Publisher PDF posted after 12 months as allowed by the publisher's policy at https://www.asbmb.org/journals-news/editorial-policies.
DOI of Published Version
This research was originally published in: J Lipid Res. 2009 Nov;50(11):2258-64. doi: 10.1194/jlr.M900107-JLR200. Epub 2009 Jun 5. Link to article on publisher's site
Journal of lipid research
Diczfalusy U, Olofsson KE, Carlsson A, Gong M, Golenbock DT, Rooyackers O, Flaring U, Bjorkbacka H. (2009). Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide. Infectious Diseases and Immunology Publications. https://doi.org/10.1194/jlr.M900107-JLR200. Retrieved from https://escholarship.umassmed.edu/infdis_pp/391