Oxysterols/oxysterol receptors have been shown to modulate several immune cell subsets, such as macrophages, T-cells and B-cells, neutrophils and dendritic cells (DCs). They participate in the control of several pathologic processes, that is, infectious diseases, atherosclerosis and autoimmunity. Moreover, some oxysterols have also been shown to favor tumor progression by dampening the antitumor immune response. The cellular responses generated by oxysterols depend on the engagement of Liver X Receptor (LXR) α and/or β isoforms, which induce activation of target genes or trans-repression of pro-inflammatory gene transcription. Recently, some reports have described a different mechanism of action of oxysterols, mediated by the engagement of G-Protein Coupled Receptors. Here, we summarize LXR-dependent and LXR-independent responses of oxysterols on immune cells with possible effects on tumor development.
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http://dx.doi.org/10.1016/j.coph.2012.07.003 | DOI Listing |
Science
January 2025
Center for Pulmonary Vascular Biology and Medicine, Pittsburgh, Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 () deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes.
View Article and Find Full Text PDFFront Pediatr
January 2025
Division of Metabolic Diseases and Hepatology, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.
Acid sphingomyelinase deficiency (ASMD) is a rare, progressive lysosomal storage disorder resulting from a deficiency in acid sphingomyelinase, leading to sphingomyelin accumulation and multi-organ damage. ASMD presents a broad phenotypic spectrum with a continuum of severity, making it challenging to predict the phenotype in very young children and differentiate between acute and chronic neurovisceral disease. No disease-specific treatments existed for ASMD.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
School of Public Health, Capital Medical University, Beijing 100069, China.
Oxysterols, as metabolites of cholesterol, play a key role in cholesterol homeostasis, autophagosome formation, and regulation of immune responses. Disorders in oxysterol metabolism are closely related to the pathogenesis of neurodegenerative diseases. To systematically investigate the profound molecular regulatory mechanisms of neurodegenerative diseases, it is necessary to quantify oxysterols and their metabolites in central and peripheral biospecimens simultaneously and accurately.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Res
January 2025
School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia. Electronic address:
Cholesterol is an essential lipid that ensures the functional integrity of mammalian cells. Most cells acquire cholesterol via endocytosis of low-density lipoproteins (LDL). Upon reaching late endosomes/lysosomes (LE/Lys), incoming ligands, including LDL-derived cholesterol, are distributed to other organelles.
View Article and Find Full Text PDFPflugers Arch
January 2025
Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, 2/31 Lobachevsky St, Kazan, 420111, RT, Russia.
Many synaptic vesicles undergo exocytosis in motor nerve terminals during neuromuscular communication. Endocytosis then recovers the synaptic vesicle pool and presynaptic membrane area. The kinetics of endocytosis may shape neuromuscular transmission, determining its long-term reliability.
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