{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T01:06:17Z","timestamp":1775610377062,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo\u2014FAPESP","award":["#2024\/03414-5"],"award-info":[{"award-number":["#2024\/03414-5"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo\u2014FAPESP","award":["#2022\/07287-2"],"award-info":[{"award-number":["#2022\/07287-2"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo\u2014FAPESP","award":["#2023\/07776-6"],"award-info":[{"award-number":["#2023\/07776-6"]}]},{"name":"Coordination for the Improvement of Higher Educational Personnel","award":["CAPES-Finance Code 001"],"award-info":[{"award-number":["CAPES-Finance Code 001"]}]},{"name":"National Council for Scientific and Technological Development\u2014CNPq","award":["#310683\/2025-4"],"award-info":[{"award-number":["#310683\/2025-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Membranes"],"abstract":"<jats:p>Sphingolipids (SL) are essential structural and bioactive components of cell membranes, remarkably involved in inflammatory signaling and membrane dynamics. Dysregulation of SL metabolism contributes to pathological inflammation and cellular stress. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (FXT), are known inhibitors of acid sphingomyelinase (aSMase), although their impact on macrophage SL remodeling and inflammatory responses remains unclear. Here, we investigated the modulation of FXT on SL species composition and inflammatory activation in THP-1-derived macrophages stimulated with inactivated SARS-CoV-2 particles, which is a model of viral-induced inflammation. Sphingolipidomic profiling revealed that FXT pre-treatment markedly reduced ceramide (Cer) species while increasing sphingomyelin (SM) and sphingosine-1-phosphate (S1P) levels, consistent with inhibition of the aSMase-Cer axis. These changes were accompanied by attenuation of proinflammatory components, including interleucin (IL)-6, IL-1\u03b2, and matrix metalloproteinase (MMP)-9, indicating that SL remodeling correlates with reduced macrophage activation. Despite pronounced alterations in membrane lipid composition, the quantification of extracellular vesicles (EVs) released by FXT-treated macrophages remained unchanged, however the EVs size distribution was smaller compared to non-treated cells. Altogether, our findings demonstrate that FXT reshapes SL metabolism and lipid membrane composition, thereby diminishing macrophage activation without affecting EVs biogenesis. This study emphasizes the immunometabolic role of SL on membrane reprogramming as a mechanism by which pharmacological aSMase inhibition modulates viral inflammation responses.<\/jats:p>","DOI":"10.3390\/membranes16030098","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T15:29:53Z","timestamp":1772724593000},"page":"98","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fluoxetine Reshapes Macrophage Membrane Sphingolipids and Inflammatory Response Without Affecting Extracellular Vesicle Biogenesis upon Inactivated SARS-CoV-2 Stimulation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8776-5417","authenticated-orcid":false,"given":"Jonatan C. S.","family":"de Carvalho","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Faculdade de Medicina de Ribeir\u00e3o Preto\u2014FMRP, Universidade de S\u00e3o Paulo\u2014USP, Ribeirao Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2109-7484","authenticated-orcid":false,"given":"Pedro","family":"Nobre-Azevedo","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Faculdade de Medicina de Ribeir\u00e3o Preto\u2014FMRP, Universidade de S\u00e3o Paulo\u2014USP, Ribeirao Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro V.","family":"da Silva-Neto","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lises Cl\u00ednicas, Toxicol\u00f3gicas e Bromatol\u00f3gicas, Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto\u2014FCFRP, Universidade de S\u00e3o Paulo\u2014USP, Ribeirao Preto 14040-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca T. M.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Faculdade de Medicina de Ribeir\u00e3o Preto\u2014FMRP, Universidade de S\u00e3o Paulo\u2014USP, Ribeirao Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7883-1443","authenticated-orcid":false,"given":"Lucas A.","family":"Tavares","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa em Virologia, Departamento de Biologia Celular e Molecular e Bioagentes Patog\u00eanicos, Faculdade de Medicina de Ribeir\u00e3o Preto\u2014FMRP, Universidade de S\u00e3o Paulo\u2014USP, Ribeirao Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana M.","family":"Toro","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa em Virologia, Departamento de Biologia Celular e Molecular e Bioagentes Patog\u00eanicos, Faculdade de Medicina de Ribeir\u00e3o Preto\u2014FMRP, Universidade de S\u00e3o Paulo\u2014USP, Ribeirao Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrews O.","family":"Borges","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Imunologia B\u00e1sica e Aplicada\u2014PPGIBA, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal do Amazonas\u2014UFAM, Manaus 69080-900, AM, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3863-6800","authenticated-orcid":false,"given":"Murillo A.","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Faculdade de Medicina de Ribeir\u00e3o Preto\u2014FMRP, Universidade de S\u00e3o Paulo\u2014USP, Ribeirao Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0978-410X","authenticated-orcid":false,"given":"Eurico","family":"Arruda","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa em Virologia, Departamento de Biologia Celular e Molecular e Bioagentes Patog\u00eanicos, Faculdade de Medicina de Ribeir\u00e3o Preto\u2014FMRP, Universidade de S\u00e3o Paulo\u2014USP, Ribeirao Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8902-5962","authenticated-orcid":false,"given":"Ronaldo B.","family":"Martins","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lises Cl\u00ednicas, Toxicol\u00f3gicas e Bromatol\u00f3gicas, Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto\u2014FCFRP, Universidade de S\u00e3o Paulo\u2014USP, Ribeirao Preto 14040-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3782-3698","authenticated-orcid":false,"given":"Fausto","family":"Almeida","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Faculdade de Medicina de Ribeir\u00e3o Preto\u2014FMRP, Universidade de S\u00e3o Paulo\u2014USP, Ribeirao Preto 14049-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos A.","family":"Sorgi","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Faculdade de Medicina de Ribeir\u00e3o Preto\u2014FMRP, Universidade de S\u00e3o Paulo\u2014USP, Ribeirao Preto 14049-900, SP, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Imunologia B\u00e1sica e Aplicada\u2014PPGIBA, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal do Amazonas\u2014UFAM, Manaus 69080-900, AM, Brazil"},{"name":"Departamento de Qu\u00edmica, Faculdade de Filosofia, Ci\u00eancias e Letras de Ribeir\u00e3o Preto\u2014FFCLRP, Universidade de S\u00e3o Paulo\u2014USP, Ribeirao Preto 14040-901, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6197","DOI":"10.1021\/bi00417a001","article-title":"Lipid Sorting in Epithelial Cells","volume":"27","author":"Simons","year":"1988","journal-title":"Biochemistry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/35036052","article-title":"Lipid Rafts and Signal Transduction","volume":"1","author":"Simons","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","first-page":"177","article-title":"Lipid Rafts in Exosome Biogenesis","volume":"85","author":"Skryabin","year":"2020","journal-title":"Biochemistry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"jcs260887","DOI":"10.1242\/jcs.260887","article-title":"The Role of Lipid Rafts in Vesicle Formation","volume":"136","author":"Sapon","year":"2023","journal-title":"J. Cell Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1194\/jlr.E600002-JLR200","article-title":"Rafts Defined: A Report on the Keystone Symposium on Lipid Rafts and Cell Function","volume":"47","author":"Pike","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41580-023-00576-0","article-title":"Context-Specific Regulation of Extracellular Vesicle Biogenesis and Cargo Selection","volume":"24","author":"Dixson","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1194\/jlr.M500103-JLR200","article-title":"Domain-Specific Lipid Distribution in Macrophage Plasma Membranes","volume":"46","author":"Gaus","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1016\/j.celrep.2015.05.006","article-title":"The Lipid-Modifying Enzyme SMPDL3B Negatively Regulates Innate Immunity","volume":"11","author":"Heinz","year":"2015","journal-title":"Cell Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nature13475","article-title":"Sphingolipid Metabolites in Inflammatory Disease","volume":"510","author":"MacEyka","year":"2014","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev-physiol-031620-093815","article-title":"Ceramides in Metabolism: Key Lipotoxic Players","volume":"83","author":"Chaurasia","year":"2021","journal-title":"Annu. Rev. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/s12944-025-02642-2","article-title":"Ceramide Signaling in Immunity: A Molecular Perspective","volume":"24","author":"Thakkar","year":"2025","journal-title":"Lipids Health Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/s12276-023-01018-9","article-title":"Functional Roles of Sphingolipids in Immunity and Their Implication in Disease","volume":"55","author":"Lee","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1515\/hsz-2014-0305","article-title":"The Role of Sphingolipids in Endothelial Barrier Function","volume":"396","author":"Jernigan","year":"2015","journal-title":"Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100899","DOI":"10.1016\/j.jlr.2025.100899","article-title":"Resolving vs. Non-Resolving Sphingolipid Dynamics During Macrophage Activation: A Time-Resolved Metabolic Analysis","volume":"66","author":"Chiappa","year":"2025","journal-title":"J. Lipid Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Perales, A., Escribese, M.M., Garrido-Arandia, M., Obeso, D., Izquierdo-Alvarez, E., Tome-Amat, J., and Barber, D. (2021). The Role of Sphingolipids in Allergic Disorders. Front. Allergy, 2.","DOI":"10.3389\/falgy.2021.675557"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1042\/CS20180911","article-title":"Potential Therapeutic Targets for Atherosclerosis in Sphingolipid Metabolism","volume":"133","author":"Yu","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1194\/jlr.R083915","article-title":"Role of Sphingolipids in the Biogenesis and Biological Activity of Extracellular Vesicles","volume":"59","author":"Verderio","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tcb.2015.01.004","article-title":"Ectosomes and Exosomes: Shedding the Confusion between Extracellular Vesicles","volume":"25","author":"Cocucci","year":"2015","journal-title":"Trends Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cytogfr.2023.08.006","article-title":"Role of Lipid Signalling in Extracellular Vesicles-Mediated Cell-to-Cell Communication","volume":"73","author":"Fyfe","year":"2023","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.1038\/s41467-021-24384-2","article-title":"Specificities of Exosome versus Small Ectosome Secretion Revealed by Live Intracellular Tracking of CD63 and CD9","volume":"12","author":"Mathieu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e12154","DOI":"10.1002\/jev2.12154","article-title":"Roles of Extracellular Vesicles in the Aging Microenvironment and Age-Related Diseases","volume":"10","author":"Yin","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e12233","DOI":"10.1002\/jev2.12233","article-title":"Function of Ceramide Transfer Protein for Biogenesis and Sphingolipid Composition of Extracellular Vesicles","volume":"11","author":"Crivelli","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12964-023-01103-6","article-title":"A Review of the Regulatory Mechanisms of Extracellular Vesicles-Mediated Intercellular Communication","volume":"21","author":"Liu","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e70018","DOI":"10.1111\/boc.70018","article-title":"Protrusion-Derived Extracellular Vesicles (PD-EVs) and Their Diverse Origins: Key Players in Cellular Communication, Cancer Progression, and T Cell Modulation","volume":"117","author":"Duro","year":"2025","journal-title":"Biol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"204054","DOI":"10.1016\/j.cdev.2025.204054","article-title":"Extracellular Vesicles: A Complex Array of Particles Involved in Cell-to-Cell Communication for Tissue Homeostasis","volume":"184","author":"Tartaglia","year":"2025","journal-title":"Cells Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.bbalip.2013.10.004","article-title":"Exosomes as New Vesicular Lipid Transporters Involved in Cell-Cell Communication and Various Pathophysiologies","volume":"1841","author":"Record","year":"2014","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1002\/jnr.23798","article-title":"Port-to-Port Delivery: Mobilization of Toxic Sphingolipids via Extracellular Vesicles","volume":"94","author":"Scesa","year":"2016","journal-title":"J. Neurosci. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1126\/science.1153124","article-title":"Ceramide Triggers Budding of Exosome Vesicles into Multivesicular Endosomes","volume":"319","author":"Trajkovic","year":"2008","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1194\/jlr.R084343","article-title":"Exosomal Lipid Composition and the Role of Ether Lipids and Phosphoinositides in Exosome Biology","volume":"60","author":"Skotland","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e70164","DOI":"10.1002\/jev2.70164","article-title":"Sphingolipids in Extracellular Vesicles Released From the Skeletal Muscle Plasma Membrane Control Muscle Stem Cell Fate During Muscle Regeneration","volume":"14","author":"Hakkar","year":"2025","journal-title":"J. Extracell. Vesicles"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7098","DOI":"10.1038\/s41380-021-01254-3","article-title":"Repurposing Antidepressants Inhibiting the Sphingomyelinase Acid\/Ceramide System against COVID-19: Current Evidence and Potential Mechanisms","volume":"26","author":"Hoertel","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"503079","DOI":"10.1155\/2015\/503079","article-title":"Alterations of the Ceramide Metabolism in the Peri-Infarct Cortex are Independent of the Sphingomyelinase Pathway and not Influenced by the Acid Sphingomyelinase Inhibitor Fluoxetine","volume":"2015","author":"Brunkhorst","year":"2015","journal-title":"Neural Plast."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"da Silva-Neto, P.V., de Carvalho, J.C.S., Toro, D.M., Oliveira, B.T.M., Cominal, J.G., Castro, R.C., Almeida, M.A., Prado, C.M., Arruda, E., and Frantz, F.G. (2025). TREM-1-Linked Inflammatory Cargo in SARS-CoV-2-Stimulated Macrophage Extracellular Vesicles Drives Cellular Senescence and Impairs Antibacterial Defense. Viruses, 17.","DOI":"10.3390\/v17050610"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"115732","DOI":"10.1016\/j.ab.2024.115732","article-title":"High-Resolution Targeted Mass Spectrometry for Comprehensive Quantification of Sphingolipids: Clinical Applications and Characterization of Extracellular Vesicles","volume":"698","author":"Felippe","year":"2025","journal-title":"Anal. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Toro, D.M., da Silva-Neto, P.V., de Carvalho, J.C.S., Fuzo, C.A., P\u00e9rez, M.M., Pimentel, V.E., Fraga-Silva, T.F.C., Oliveira, C.N.S., Caruso, G.R., and Vilela, A.F.L. (2023). Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19. Cells, 12.","DOI":"10.3390\/cells12151938"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal Information for Studies of Extracellular Vesicles (MISEV2023): From Basic to Advanced Approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1083\/jcb.201003053","article-title":"Exocytosis of Acid Sphingomyelinase by Wounded Cells Promotes Endocytosis and Plasma Membrane Repair","volume":"189","author":"Tam","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1378056","DOI":"10.1080\/20013078.2017.1378056","article-title":"Neutral Sphingomyelinases Control Extracellular Vesicles Budding from the Plasma Membrane","volume":"6","author":"Menck","year":"2017","journal-title":"J. Extracell. Vesicles"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Li, C., Guo, S., Pang, W., and Zhao, Z. (2020). Crosstalk Between Acid Sphingomyelinase and Inflammasome Signaling and Their Emerging Roles in Tissue Injury and Fibrosis. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00378"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/nm.3214","article-title":"Acid Sphingomyelinase-Ceramide System Mediates Effects of Antidepressant Drugs","volume":"19","author":"Gulbins","year":"2013","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"100142","DOI":"10.1016\/j.xcrm.2020.100142","article-title":"Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells","volume":"1","author":"Carpinteiro","year":"2020","journal-title":"Cell Rep. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.4049\/jimmunol.173.5.3193","article-title":"Ceramide Inhibits IL-2 Production by Preventing Protein Kinase C-Dependent NF-\u039aB Activation: Possible Role in Protein Kinase C\u03b8 Regulation","volume":"173","author":"Abboushi","year":"2004","journal-title":"J. Immunol."},{"key":"ref_43","first-page":"100177","article-title":"Exploring SK\/S1P\/S1PR Pathway as a Target for Antiviral Drug Development","volume":"11","author":"Swain","year":"2024","journal-title":"Health Sci. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ermini, L., Farrell, A., Alahari, S., Ausman, J., Park, C., Sallais, J., Melland-Smith, M., Porter, T., Edson, M., and Nevo, O. (2021). Ceramide-Induced Lysosomal Biogenesis and Exocytosis in Early-Onset Preeclampsia Promotes Exosomal Release of SMPD1 Causing Endothelial Dysfunction. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.652651"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0092-8674(00)80448-1","article-title":"Acidic Sphingomyelinase Mediates Entry of N. Gonorrhoeae into Nonphagocytic Cells","volume":"91","author":"Gulbins","year":"1997","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1084\/jem.20102518","article-title":"Trypanosoma Cruzi Subverts the Sphingomyelinase-Mediated Plasma Membrane Repair Pathway for Cell Invasion","volume":"208","author":"Fernandes","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7473","DOI":"10.1128\/JVI.00136-12","article-title":"Ebolavirus Requires Acid Sphingomyelinase Activity and Plasma Membrane Sphingomyelin for Infection","volume":"86","author":"Miller","year":"2012","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"26256","DOI":"10.1074\/jbc.M500835200","article-title":"Rhinoviruses Infect Human Epithelial Cells via Ceramide-Enriched Membrane Platforms","volume":"280","author":"Riehle","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1080\/22221751.2020.1829082","article-title":"Targeting the Endolysosomal Host-SARS-CoV-2 Interface by Clinically Licensed Functional Inhibitors of Acid Sphingomyelinase (FIASMA) Including the Antidepressant Fluoxetine","volume":"9","author":"Schloer","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.bbrc.2008.02.023","article-title":"Lipid Rafts are Involved in SARS-CoV Entry into Vero E6 Cells","volume":"369","author":"Lu","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"15174","DOI":"10.1074\/jbc.RA120.015249","article-title":"Sphingosine Prevents Binding of SARS-CoV-2 Spike to Its Cellular Receptor ACE2","volume":"295","author":"Edwards","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1465-9921-8-35","article-title":"Anti-Inflammatory Properties of Desipramine and Fluoxetine","volume":"8","author":"Roumestan","year":"2007","journal-title":"Respir. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejphar.2018.08.026","article-title":"Fluoxetine Protects against OVA Induced Bronchial Asthma and Depression in Rats","volume":"837","author":"Sherkawy","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s41392-023-01510-8","article-title":"Metabolic Alterations upon SARS-CoV-2 Infection and Potential Therapeutic Targets against Coronavirus Infection","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"111437","DOI":"10.1016\/j.biopha.2021.111437","article-title":"Fluoxetine as an Anti-Inflammatory Therapy in SARS-CoV-2 Infection","volume":"138","author":"Creeden","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.intimp.2015.02.029","article-title":"Paroxetine Differentially Modulates LPS-Induced TNF\u03b1 and IL-6 Production in Mouse Macrophages","volume":"25","author":"Durairaj","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.bbi.2006.11.006","article-title":"An Inflammatory Review of Glucocorticoid Actions in the CNS","volume":"21","author":"Sorrells","year":"2007","journal-title":"Brain Behav. Immun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.cellsig.2015.03.013","article-title":"Reactive Oxygen Species in the Tumor Niche Triggers Altered Activation of Macrophages and Immunosuppression: Role of Fluoxetine","volume":"27","author":"Ghosh","year":"2015","journal-title":"Cell. Signal."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"18397","DOI":"10.3402\/jev.v1i0.18397","article-title":"Diverse Subpopulations of Vesicles Secreted by Different Intracellular Mechanisms are Present in Exosome Preparations Obtained by Differential Ultracentrifugation","volume":"1","author":"Bobrie","year":"2012","journal-title":"J. Extracell. Vesicles"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1126\/science.1152505","article-title":"Local Positive Feedback Regulation Determines Cell Shape in Root Hair Cells","volume":"319","author":"Takeda","year":"2008","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1186\/s12964-023-01291-1","article-title":"Neutral Sphingomyelinase Inhibition Promotes Local and Network Degeneration in Vitro and in Vivo","volume":"21","author":"Risner","year":"2023","journal-title":"Cell Commun. Signal."}],"container-title":["Membranes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0375\/16\/3\/98\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T15:51:24Z","timestamp":1772725884000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0375\/16\/3\/98"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":62,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["membranes16030098"],"URL":"https:\/\/doi.org\/10.3390\/membranes16030098","relation":{},"ISSN":["2077-0375"],"issn-type":[{"value":"2077-0375","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]}}}