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Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide

Diczfalusy, Ulf; Berg, Katarina LU ; Carlsson, Ann-Margreth LU ; Gong, Mei; Golenbock, Douglas T.; Rooyackers, Olav; Flaring, Urban and Björkbacka, Harry LU (2009) In Journal of Lipid Research 50(11). p.2258-2264
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... (More)
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.-Diczfalusy, U., K. E. Olofsson, A- M. Carlsson, M. Gong, D. T. Golenbock, O. Rooyackers, U. Flaring, and H. Bjorkbacka. Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide. J. Lipids Res. 2009. 50: 2258-2264. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
sepsis, inflammation, endotoxin, 25-hydroxycholesterol, oxysterols, macrophages
in
Journal of Lipid Research
volume
50
issue
11
pages
2258 - 2264
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • wos:000270860900014
  • scopus:70349757041
ISSN
1539-7262
DOI
10.1194/jlr.M900107-JLR200
language
English
LU publication?
yes
id
ce8ed87d-6cc5-4d3f-b4ef-d94a235c5b96 (old id 1506271)
date added to LUP
2009-11-23 16:00:27
date last changed
2017-12-10 03:47:27
@article{ce8ed87d-6cc5-4d3f-b4ef-d94a235c5b96,
  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.-Diczfalusy, U., K. E. Olofsson, A- M. Carlsson, M. Gong, D. T. Golenbock, O. Rooyackers, U. Flaring, and H. Bjorkbacka. Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide. J. Lipids Res. 2009. 50: 2258-2264.},
  author       = {Diczfalusy, Ulf and Berg, Katarina and Carlsson, Ann-Margreth and Gong, Mei and Golenbock, Douglas T. and Rooyackers, Olav and Flaring, Urban and Björkbacka, Harry},
  issn         = {1539-7262},
  keyword      = {sepsis,inflammation,endotoxin,25-hydroxycholesterol,oxysterols,macrophages},
  language     = {eng},
  number       = {11},
  pages        = {2258--2264},
  publisher    = {American Society for Biochemistry and Molecular Biology},
  series       = {Journal of Lipid Research},
  title        = {Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide},
  url          = {http://dx.doi.org/10.1194/jlr.M900107-JLR200},
  volume       = {50},
  year         = {2009},
}