journal article Open Access Apr 07, 2022

Effects of Oxysterols on Immune Cells and Related Diseases

Cells Vol. 11 No. 8 pp. 1251 · MDPI AG
View at Publisher Save 10.3390/cells11081251
Abstract
Oxysterols are the products of cholesterol oxidation. They have a wide range of effects on several cells, organs, and systems in the body. Oxysterols also have an influence on the physiology of the immune system, from immune cell maturation and migration to innate and humoral immune responses. In this regard, oxysterols have been involved in several diseases that have an immune component, from autoimmune and neurodegenerative diseases to inflammatory diseases, atherosclerosis, and cancer. Here, we review data on the participation of oxysterols, mainly 25-hydroxycholesterol and 7α,25-dihydroxycholesterol, in the immune system and related diseases. The effects of these oxysterols and main oxysterol receptors, LXR and EBI2, in cells of the immune system (B cells, T cells, macrophages, dendritic cells, oligodendrocytes, and astrocytes), and in immune-related diseases, such as neurodegenerative diseases, intestinal diseases, cancer, respiratory diseases, and atherosclerosis, are discussed.
Topics

No keywords indexed for this article. Browse by subject →

References
161
[1]
Horton "Srebps: Activators of the complete program of cholesterol and fatty acid synthesis in the liver" J. Clin. Investig. (2002) 10.1172/jci0215593
[2]
Griffiths "Sterols, oxysterols and accessible cholesterol: Signalling for homeostasis, in immunity and during development" Front. Physiol. (2021) 10.3389/fphys.2021.723224
[3]
Bah "Immune oxysterols: Role in mycobacterial infection and inflammation" J. Steroid Biochem. Mol. Biol. (2017) 10.1016/j.jsbmb.2016.04.015
[4]
Shahoei "Nuclear receptors, cholesterol homeostasis and the immune system" J. Steroid Biochem. Mol. Biol. (2019) 10.1016/j.jsbmb.2019.04.013
[5]
Griffiths "An update on oxysterol biochemistry: New discoveries in lipidomics" Biochem. Biophys. Res. Commun. (2018) 10.1016/j.bbrc.2018.02.019
[6]
York "Subverting sterols: Rerouting an oxysterol-signaling pathway to promote tumor growth" J. Exp. Med. (2013) 10.1084/jem.20131335
[7]
Ruiz "Interrelationship between atp-binding cassette transporters and oxysterols" Biochem. Pharmacol. (2013) 10.1016/j.bcp.2013.02.033
[8]
Maselli "Outside-in, inside-out: Proteomic analysis of endothelial stress mediated by 7-ketocholesterol" Chem. Phys. Lipids (2017) 10.1016/j.chemphyslip.2017.06.008
[9]
Griffiths "Current trends in oxysterol research" Biochem. Soc. Trans. (2016) 10.1042/bst20150255
[10]
Reinmuth, L., Hsiao, C.C., Hamann, J., Rosenkilde, M., and Mackrill, J. (2021). Multiple targets for oxysterols in their regulation of the immune system. Cells, 10. 10.3390/cells10082078
[11]
Duc, D., Vigne, S., and Pot, C. (2019). Oxysterols in autoimmunity. Int. J. Mol. Sci., 20. 10.3390/ijms20184522
[12]
Park "Cholesterol 25-hydroxylase production by dendritic cells and macrophages is regulated by type i interferons" J. Leukoc. Biol. (2010) 10.1189/jlb.0610318
[13]
Levy "Short-term effects of 7-ketocholesterol on human adipose tissue mesenchymal stem cells in vitro" Biochem. Biophys. Res. Commun. (2014) 10.1016/j.bbrc.2014.01.132
[14]
Stern "7-ketocholesterol overcomes drug resistance in chronic myeloid leukemia cell lines beyond mdr1 mechanism" J. Proteom. (2017) 10.1016/j.jprot.2016.06.011
[15]
Levy "Oxysterols selectively promote short-term apoptosis in tumor cell lines" Biochem. Biophys. Res. Commun. (2018) 10.1016/j.bbrc.2018.10.008
[16]
Favero "Cell internalization of 7-ketocholesterol-containing nanoemulsion through ldl receptor reduces melanoma growth in vitro and in vivo: A preliminary report" Oncotarget (2018) 10.18632/oncotarget.24389
[17]
Silva "Oxysterols in adipose tissue-derived mesenchymal stem cell proliferation and death" J. Steroid Biochem. Mol. Biol. (2017) 10.1016/j.jsbmb.2016.04.017
[18]
Levy "7-ketocholesterol and cholestane-triol increase expression of smo and lxrα signaling pathways in a human breast cancer cell line" Biochem. Biophys. Rep. (2019)
[19]
De Freitas, F.A., Levy, D., Zarrouk, A., Lizard, G., and Bydlowski, S.P. (2021). Impact of oxysterols on cell death, proliferation, and differentiation induction: Current status. Cells, 10. 10.3390/cells10092301
[20]
Prunet "Comparison of the cytotoxic, pro-oxidant and pro-inflammatory characteristics of different oxysterols" Cell Biol. Toxicol. (2005) 10.1007/s10565-005-0141-2
[21]
Prunet "Multiplexed flow cytometric analyses of pro- and anti-inflammatory cytokines in the culture media of oxysterol-treated human monocytic cells and in the sera of atherosclerotic patients" Cytometry. Part A J. Int. Soc. Anal. Cytol. (2006) 10.1002/cyto.a.20272
[22]
Rydberg "Hypoxia increases 25-hydroxycholesterol-induced interleukin-8 protein secretion in human macrophages" Atherosclerosis (2003) 10.1016/s0021-9150(03)00302-2
[23]
Zarrouk "Involvement of oxysterols in age-related diseases and ageing processes" Ageing Res. Rev. (2014) 10.1016/j.arr.2014.09.006
[24]
Dias "Inflammation, lipid (per)oxidation, and redox regulation" Antioxid. Redox Signal. (2020) 10.1089/ars.2020.8022
[25]
Galea "Oxidative stress underlying axonal degeneration in adrenoleukodystrophy: A paradigm for multifactorial neurodegenerative diseases?" Biochim. Biophys. Acta (2012) 10.1016/j.bbadis.2012.02.005
[26]
Ragot "A-tocopherol impairs 7-ketocholesterol-induced caspase-3-dependent apoptosis involving gsk-3 activation and mcl-1 degradation on 158n murine oligodendrocytes" Chem. Phys. Lipids (2011) 10.1016/j.chemphyslip.2011.04.014
[27]
Ragot "Absence of correlation between oxysterol accumulation in lipid raft microdomains, calcium increase, and apoptosis induction on 158n murine oligodendrocytes" Biochem. Pharmacol. (2013) 10.1016/j.bcp.2013.02.028
[28]
Hubler "Role of lipids in the metabolism and activation of immune cells" J. Nutr. Biochem. (2016) 10.1016/j.jnutbio.2015.11.002
[29]
Lathe, R., Sapronova, A., and Kotelevtsev, Y. (2014). Atherosclerosis and alzheimer—Diseases with a common cause? Inflammation, oxysterols, vasculature. BMC Geriatr., 14. 10.1186/1471-2318-14-36
[30]
25-Hydroxycholesterols in innate and adaptive immunity

Jason G. Cyster, Eric V. Dang, Andrea Reboldi et al.

Nature Reviews Immunology 2014 10.1038/nri3755
[31]
Varaksa "Metabolic fate of human immunoactive sterols in mycobacterium tuberculosis" J. Mol. Biol. (2021) 10.1016/j.jmb.2020.166763
[32]
Traversari "Control of the immune system by oxysterols and cancer development" Curr. Opin. Pharmacol. (2012) 10.1016/j.coph.2012.07.003
[33]
Mutemberezi "Oxysterols: From cholesterol metabolites to key mediators" Prog. Lipid Res. (2016) 10.1016/j.plipres.2016.09.002
[34]
Traversari "Lxr-dependent and -independent effects of oxysterols on immunity and tumor growth" Eur. J. Immunol. (2014) 10.1002/eji.201344292
[35]
Bensinger "Lxr signaling couples sterol metabolism to proliferation in the acquired immune response" Cell (2008) 10.1016/j.cell.2008.04.052
[36]
Fang "Expression of nr1h3 in endometrial carcinoma and its effect on the proliferation of ishikawa cells in vitro" OncoTargets Ther. (2019) 10.2147/ott.s180534
[37]
Yang "Nuclear receptors, metabolism, and the circadian clock" Cold Spring Harb. Symp. Quant. Biol. (2007) 10.1101/sqb.2007.72.058
[38]
Jarvis, S., Williamson, C., and Bevan, C.L. (2019). Liver x receptors and male (in)fertility. Int. J. Mol. Sci., 20. 10.3390/ijms20215379
[39]
Glass "The coregulator exchange in transcriptional functions of nuclear receptors" Genes Dev. (2000) 10.1101/gad.14.2.121
[40]
Villablanca "Tumor-mediated liver x receptor-alpha activation inhibits cc chemokine receptor-7 expression on dendritic cells and dampens antitumor responses" Nat. Med. (2010) 10.1038/nm.2074
[41]
Abildayeva "24(s)-hydroxycholesterol participates in a liver x receptor-controlled pathway in astrocytes that regulates apolipoprotein e-mediated cholesterol efflux" J. Biol. Chem. (2006) 10.1074/jbc.m601019200
[42]
Mukhutdinova "Oxysterol modulates neurotransmission via liver-x receptor/no synthase-dependent pathway at the mouse neuromuscular junctions" Neuropharmacology (2019) 10.1016/j.neuropharm.2019.03.018
[43]
Ishikawa "Lxrβ/estrogen receptor-α signaling in lipid rafts preserves endothelial integrity" J. Clin. Investig. (2013) 10.1172/jci66533
[44]
Unsworth "Non-genomic effects of nuclear receptors: Insights from the anucleate platelet" Cardiovasc. Res. (2018) 10.1093/cvr/cvy044
[45]
Zakyrjanova "Immune-related oxysterol modulates neuromuscular transmission via non-genomic liver x receptor-dependent mechanism" Free Radic. Biol. Med. (2021) 10.1016/j.freeradbiomed.2021.08.013
[46]
Pereira "Ebi2 mediates b cell segregation between the outer and centre follicle" Nature (2009) 10.1038/nature08226
[47]
Barington "Ebi2 in splenic and local immune responses and in autoimmunity" J. Leukoc. Biol. (2018) 10.1002/jlb.2vmr1217-510r
[48]
Smethurst "Ligand modulation of the epstein-barr virus-induced seven-transmembrane receptor ebi2: Identification of a potent and efficacious inverse agonist" J. Biol. Chem. (2011) 10.1074/jbc.m110.196345
[49]
Daugvilaite "Oxysterol-ebi2 signaling in immune regulation and viral infection" Eur. J. Immunol. (2014) 10.1002/eji.201444493
[50]
Birkenbach "Epstein-barr virus-induced genes: First lymphocyte-specific g protein-coupled peptide receptors" J. Virol. (1993) 10.1128/jvi.67.4.2209-2220.1993

Showing 50 of 161 references

Metrics
46
Citations
161
References
Details
Published
Apr 07, 2022
Vol/Issue
11(8)
Pages
1251
License
View
Authors
Cite This Article
Fábio Alessandro de Freitas, Débora Levy, Cadiele Oliana Reichert, et al. (2022). Effects of Oxysterols on Immune Cells and Related Diseases. Cells, 11(8), 1251. https://doi.org/10.3390/cells11081251