Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide

Journal of Lipid Research

Olav Rooyackers¹  Ann-Margreth Carlsson²  Katarina E. Olofsson²  Ulf Diczfalusy³  Mei Gong⁴  Douglas T. Golenbock⁴  Urban Fläring⁵  Harry Björkbacka⁶ 

[1] Department of Anesthesia and Intensive Care, Karolinska University Hospital, Stockholm, Sweden;Department of Clinical Sciences, Malmö University Hospital, Lund University, Sweden;Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden;Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA;Department of Pediatric Anaesthesia and Intensive Care, Karolinska University Hospital, Stockholm, Sweden;To whom correspondence should be addressed;

关键词: 25-hydroxycholesterol;    oxysterols;    endotoxin;    inflammation;    sepsis;    macrophages;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown