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Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide

In English

Författare

  • Ulf Diczfalusy
  • Katarina Berg
  • Ann-Margreth Carlsson
  • Mei Gong
  • Douglas T. Golenbock
  • Olav Rooyackers
  • Urban Flaring
  • Harry Björkbacka

Summary, in English

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.

Publiceringsår

2009

Språk

Engelska

Sidor

2258-2264

Publikation/Tidskrift/Serie

Journal of Lipid Research

Volym

50

Issue

11

Dokumenttyp

Artikel i tidskrift

Förlag

American Society for Biochemistry and Molecular Biology

Ämne

  • Cardiac and Cardiovascular Systems

Nyckelord

  • sepsis
  • inflammation
  • endotoxin
  • 25-hydroxycholesterol
  • oxysterols
  • macrophages

Status

Published

Forskningsgrupp

  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Övrigt

  • ISSN: 1539-7262