Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide
Open accessAbstract
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.
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Ch25h, the enzyme that hydroxylates cholesterol to 25HC, is markedly upregulated by toll-like receptor activation of macrophages.
“Ch25h, the enzyme that hydroxylates cholesterol to 25-hydroxycholesterol (25HC) (9) is markedly upregulated by toll-like receptor activation of macrophages (10,11).”
From Regulation of astrocyte lipid metabolism and ApoE secretion by the microglial oxysterol, 25-hydroxycholesterol (2023) · cites this paper as [11]
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Cashikar, A. G., Toral-Rios, D., Timm, D., Romero, J., Strickland, M., Long, J. M., Han, X., Holtzman, D. M., & Paul, S. M. (2023) · Journal of Lipid Research · doi:10.1016/j.jlr.2023.100350 · Cited by 72 · see citing works
- Authors
- Diczfalusy, U., Olofsson, K. E., Carlsson, A.-M., Gong, M., Golenbock, D. T., Rooyackers, O., Fläring, U., & Björkbacka, H.
- Affiliations
- Karolinska University Hospital (SE)
- Lund University (SE)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Björkbacka, Harry
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 50
- Issue
- 11
- Pages
- 2258-2264
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC2759831
- OpenAlex
- W2135148910
- Cited by
- 204
- References
- 0
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 11 · 2023: 18 · 2022: 11 · 2021: 13 · 2020: 12 · 2019: 12 · 2018: 12 · 2017: 7 · 2016: 17 · 2015: 12 · 2014: 19 · 2013: 9 · 2012: 15
- FWCI
- 10.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- cholesterol 25-hydroxylase, lipopolysaccharide, macrophages, 25-hydroxycholesterol, TLR4 signaling, RANTES, endotoxin, inflammation, cholesterol homeostasis, gene upregulation
- MeSH terms
- Adult, Animals, Bone Marrow Cells, Cell Line, Dose-Response Relationship, Drug, Humans, Hydroxycholesterols, Lipopolysaccharides, Macrophages, Male, Mice, Inbred C57BL, Steroid Hydroxylases, Signal Transduction, Up-Regulation, Gene Expression Regulation, Enzymologic, Mice, Knockout, Chemokine CCL5, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Toll-Like Receptor 4, Mice, Myeloid Differentiation Factor 88, Young Adult
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