Document Detail


Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide.
MedLine Citation:
PMID:  19502589     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ulf Diczfalusy; Katarina E Olofsson; Ann-Margreth Carlsson; Mei Gong; Douglas T Golenbock; Olav Rooyackers; Urban Fläring; Harry Björkbacka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-05
Journal Detail:
Title:  Journal of lipid research     Volume:  50     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-12-07     Completed Date:  2010-03-16     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2258-64     Citation Subset:  IM    
Affiliation:
Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Bone Marrow Cells / cytology,  drug effects,  metabolism
Cell Line
Chemokine CCL5 / metabolism
Dose-Response Relationship, Drug
Gene Expression Regulation, Enzymologic / drug effects
Humans
Hydroxycholesterols / pharmacology
Lipopolysaccharides / pharmacology*
Macrophages / cytology,  drug effects*,  metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88 / genetics,  metabolism
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects
Steroid Hydroxylases / blood,  genetics*
Toll-Like Receptor 4 / metabolism
Up-Regulation / drug effects
Young Adult
Chemical
Reg. No./Substance:
0/Ccl5 protein, mouse; 0/Chemokine CCL5; 0/Hydroxycholesterols; 0/Lipopolysaccharides; 0/Myd88 protein, mouse; 0/Myeloid Differentiation Factor 88; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; 767JTD2N31/25-hydroxycholesterol; EC 1.14.-/Steroid Hydroxylases; EC 1.14.99.38/cholesterol 25-hydroxylase
Comments/Corrections

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