Evidence map›Paper›PMID 41893283›Full record

ArticleMembranes2026

Fluoxetine Reshapes Macrophage Membrane Sphingolipids and Inflammatory Response Without Affecting Extracellular Vesicle Biogenesis upon Inactivated SARS-CoV-2 Stimulation.

Jonatan C S de Carvalho, Pedro Nobre-Azevedo, Pedro V da Silva-Neto, Bianca T M Oliveira, Lucas A Tavares, Diana M Toro, Andrews O Borges, Murillo A Nascimento, Eurico Arruda, Ronaldo B Martins and 2 more

Abstract read
In one paragraph

Article in Membranes, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Jonatan C S de CarvalhoDepartamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirao Preto 14049-900, SP, Brazil.ORCID 0000-0001-8776-5417
Pedro Nobre-AzevedoDepartamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirao Preto 14049-900, SP, Brazil.ORCID 0000-0002-2109-7484
Pedro V da Silva-NetoDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-FCFRP, Universidade de São Paulo-USP, Ribeirao Preto 14040-903, SP, Brazil.
Bianca T M OliveiraDepartamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirao Preto 14049-900, SP, Brazil.
Lucas A TavaresCentro de Pesquisa em Virologia, Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirao Preto 14049-900, SP, Brazil.ORCID 0000-0001-7883-1443
Diana M ToroCentro de Pesquisa em Virologia, Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirao Preto 14049-900, SP, Brazil.
Andrews O BorgesPrograma de Pós-Graduação em Imunologia Básica e Aplicada-PPGIBA, Instituto de Ciências Biológicas, Universidade Federal do Amazonas-UFAM, Manaus 69080-900, AM, Brazil.
Murillo A NascimentoDepartamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirao Preto 14049-900, SP, Brazil.ORCID 0000-0002-3863-6800
Eurico ArrudaCentro de Pesquisa em Virologia, Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirao Preto 14049-900, SP, Brazil.ORCID 0000-0002-0978-410X
Ronaldo B MartinsDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-FCFRP, Universidade de São Paulo-USP, Ribeirao Preto 14040-903, SP, Brazil.ORCID 0000-0002-8902-5962
Fausto AlmeidaDepartamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirao Preto 14049-900, SP, Brazil.ORCID 0000-0002-3782-3698
Carlos A SorgiDepartamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto-FMRP, Universidade de São Paulo-USP, Ribeirao Preto 14049-900, SP, Brazil.

Funding

Coordination for the Improvement of Higher Educational Personnel CAPES-Finance Code 001Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP #2022/07287-2Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP #2024/03414-5Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP #2023/07776-6National Council for Scientific and Technological Development - CNPq #310683/2025-4
6 · The paper itself

Abstract

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-1β, 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.

Indexed as

extracellular vesiclesfluoxetineinflammationmacrophageSARS-CoV-2sphingolipids

Identifiers

PMID41893283
PMCPMC13027969

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.