25-Hydroxycholesterol suppresses interleukin-1–driven inflammation downstream of type I interferon
Open accessAbstract
Bad cholesterol: Bad for bacteria, too?: Why do viral infections, such as the common cold, leave people more susceptible to bacterial pneumonia? One reason is that type I interferons, secreted proteins that initiate antiviral immune responses, suppress other inflammatory molecules that protect against bacterial infection. Reboldi et al. investigated how this suppression occurs on a molecular level in mice. Interferons stimulated expression of a particular enzyme that catalyzes the production of the oxysterol 25-hydroxycholesterol (25-HC). 25-HC inhibits the function of the transcription factor SREBP, which normally drives expression of the gene that encodes interleukin-1, a secreted inflammatory protein with wide-ranging antibacterial functions. Science , this issue p. 679
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Loss of Ch25h and 25HC promotes IL-1β production in mouse macrophages, whereas 25HC amplifies IL-1β secretion in an ApoE-dependent manner in mouse microglia.
“While loss of Ch25h and 25HC promoted interleukin 1-beta production in mouse macrophages (14,15), 25HC amplified interleukin 1-beta secretion in an ApoEdependent manner in mouse microglia (8).”
From Regulation of astrocyte lipid metabolism and ApoE secretion by the microglial oxysterol, 25-hydroxycholesterol (2023) · cites this paper as [14]
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- Authors
- Reboldi, A., Dang, E. V., McDonald, J. G., Liang, G., Russell, D. W., & Cyster, J. G.
- Affiliations
- Howard Hughes Medical Institute (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Cyster, Jason G.
- ORCID
- Venue
- Science
- Published
- 2014-08-08
- Volume
- 345
- Issue
- 6197
- Pages
- 679-684
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4289637
- OpenAlex
- W1984391988
- Cited by
- 444
- References
- 1
- Citations by year
- 2026: 21 · 2025: 31 · 2024: 29 · 2023: 48 · 2022: 35 · 2021: 40 · 2020: 49 · 2019: 37 · 2018: 40 · 2017: 42 · 2016: 41 · 2015: 24 · 2014: 6
- FWCI
- 17.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (n01ai40098-3-0-0)
- National Heart, Lung, and Blood Institute (2P01HL20948, P01HL020948)
- National Institute of Allergy and Infectious Diseases (N01 AI040098, R01AI040098)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- 25-hydroxycholesterol, oxysterols, type I interferon, interleukin-1, cholesterol 25-hydroxylase, inflammasome, macrophages, inflammation, septic shock, experimental autoimmune encephalomyelitis, bacterial growth
- MeSH terms
- Animals, Encephalomyelitis, Autoimmune, Experimental, Hydroxycholesterols, Inflammation, Interferon Type I, Interleukin-1, Macrophage Activation, Macrophages, Mice, Inbred C57BL, Mice, Mutant Strains, Shock, Septic, Steroid Hydroxylases, Response Elements, Feedback, Physiological, Mice, Inflammasomes
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