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    Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide

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    J._Lipid_Res._2009_Diczfalusy_ ...
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    Authors
    Diczfalusy, Ulf
    Olofsson, Katarina E.
    Carlsson, Ann-Margreth
    Gong, Mei
    Golenbock, Douglas T.
    Rooyackers, Olav
    Flaring, Urban
    Bjorkbacka, Harry
    UMass Chan Affiliations
    Department of Medicine, Division of Infectious Diseases and Immunology
    Document Type
    Journal Article
    Publication Date
    2009-11-01
    Keywords
    25-hydroxycholesterol
    oxysterols
    endotoxin
    inflammation
    sepsis
    macrophages
    Biochemistry
    Cellular and Molecular Physiology
    Lipids
    
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    Link to Full Text
    https://doi.org/10.1194/jlr.M900107-JLR200
    Abstract
    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.
    Source

    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

    DOI
    10.1194/jlr.M900107-JLR200
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/35171
    PubMed ID
    19502589
    Related Resources

    Link to Article in PubMed

    Rights
    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.
    ae974a485f413a2113503eed53cd6c53
    10.1194/jlr.M900107-JLR200
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