ArticleProceedings of the National Academy of Sciences of the United States of America2014
25-Hydroxycholesterol acts as an amplifier of inflammatory signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
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Who cites it
150 citing papers in PubMed, 248 citations in OpenAlex.
- A CRISPR activation screen identifies CH25H as a restriction factor against influenza viruses by targeting accessible cholesterol.Emerging microbes & infections · 2026Article
- Article
- Mass Spectrometry-Based Screening Reveals Inhibitors of Cholesterol 25-Hydroxylase.ACS chemical biology · 2026Article
- Macrophage-derived oxysterols organize T helper 2 cells to suppress type 1 inflammation during pulmonary fungal infection.Science immunology · 2026Article
- Structure-activity relationships of steroid and sterol neuromodulators on inflammatory markers in a murine microglial cell line.The Journal of steroid biochemistry and molecular biology · 2026Article
- GPR183 contributes to renal macrophage infiltration and fibrosis in kidney injury.American journal of physiology. Renal physiology · 2026Article
- Review
- Dynamic regulatory mechanism of cholesterol 25-hydroxylase-mediated antiviral response in RNA virus infections.Frontiers in cellular and infection microbiology · 2026Review
- 25-Hydroxycholesterol restricts human norovirus replication in human intestinal enteroids.Journal of virology · 2025Article
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- ATG16L1 WD domain and linker regulates lipid trafficking to maintain plasma membrane integrity to limit influenza virus infection.Autophagy · 2025Article
- Spatial organization of pulmonary type 2 inflammation by a macrophage-derived cholesterol metabolite.bioRxiv : the preprint server for biology · 2025Article
- Integrated microbiome and metabolome analysis reveals altered gut microbial communities and metabolite profiles in dairy cows with subclinical mastitis.BMC microbiology · 2025Article
- Effects of acute pro-inflammatory stimulation and 25-hydroxycholesterol on hippocampal plasticity and learning involve NLRP3 inflammasome and cellular stress responses.Scientific reports · 2025Article
- Striking a balance: new perspectives on homeostatic dendritic cell maturation.Nature reviews. Immunology · 2025Review
- Lymphatic-derived oxysterols promote anti-tumor immunity and response to immunotherapy in melanoma.Nature communications · 2025Article
- Roles of 4'-International journal of molecular sciences · 2024Article
- Cholesterol sensing and metabolic adaptation in tissue immunity.Trends in immunology · 2024Review
- 25-hydroxycholesterol promotes brain cytokine production and leukocyte infiltration in a mouse model of lipopolysaccharide-induced neuroinflammation.Journal of neuroinflammation · 2024Article
- Oxysterol Induces Expression of 60 kDa Chaperone Protein on Cell Surface of Microglia.International journal of molecular sciences · 2024Article
90 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cross-talk between sterol regulatory pathways and inflammatory pathways has been demonstrated to significantly impact the development of both atherosclerosis and infectious disease. The oxysterol 25-hydroxycholesterol (25HC) plays multiple roles in lipid biosynthesis and immunity. We recently used a systems biology approach to identify 25HC as an innate immune mediator that had a predicted role in atherosclerosis and we demonstrated a role for 25HC in foam cell formation. Here, we show that this mediator also has several complex roles in the antiviral response. The host response to viruses involves gene regulatory circuits with multiple feedback loops and we show here that 25HC acts as an amplifier of inflammatory signaling in macrophages. We determined that 25HC amplifies inflammatory signaling, at least in part, by mediating the recruitment of the AP-1 components FBJ osteosarcoma oncogene (FOS) and jun proto-oncogene (JUN) to the promoters of a subset of Toll-like receptor-responsive genes. Consistent with previous reports, we found that 25HC inhibits in vitro infection of airway epithelial cells by influenza. Surprisingly, we found that deletion of Ch25h, the gene encoding the enzyme responsible for 25HC production, is protective in a mouse model of influenza infection as a result of decreased inflammatory-induced pathology. Thus, our study demonstrates, for the first time to our knowledge, that in addition to its direct antiviral role, 25HC also regulates transcriptional responses and acts as an amplifier of inflammation via AP-1 and that the resulting alteration in inflammatory response leads to increased tissue damage in mice following infection with influenza.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.