The dual effect of acetate on microglial TNF-α production
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Clinics |
Texto Completo: | https://www.revistas.usp.br/clinics/article/view/213420 |
Resumo: | Introduction: Short-Chain Fatty Acids (SCFA) are products of intestinal microbial metabolism that can reach the brain and alter microglia in health and disease contexts. However, data are conflicting on the effect of acetate, the most abundant SCFA in the blood, in these cells. Objective: The authors aimed to investigate acetate as a modulator of the inflammatory response in microglia stimulated with LPS. Method: The authors used an immortalized cell line, C8-B4, and primary cells for in vitro treatments with acetate and LPS. Cell viability was analyzed by MTT, cytokine by RT-PCR, ELISA, and flow cytometry. The authors also performed in vivo and in silico analyses to study the role of acetate and the TNF-α contribution to the development of Experimental Autoimmune Encephalomyelitis (EAE). Results: Acetate co-administered with LPS was able to exacerbate the production of pro-inflammatory cytokines at gene and protein levels in cell lines and primary culture of microglia. However, the same effects were not observed when acetate was administered alone or as pretreatment, prior to the LPS stimulus. Additionally, pharmacological inhibition of histone deacetylase concomitantly with acetate and LPS led to decreased TNF-α production. In silico analysis showed a crucial role of the TNF-α pathway in EAE development. Moreover, acetate administration in vivo during the initial phase of EAE led to a better disease outcome and reduced TNF-α production. Conclusion: Treatment with acetate was able to promote the production of TNF-α in a concomitant LPS stimulus of microglia. However, the immune modulation of microglia by acetate pretreatment may be a component in the generation of future therapies for neurodegenerative diseases. |
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The dual effect of acetate on microglial TNF-α productionAcetateMicrogliaInflammationAlzheimer DiseaseEncephalomyelitisTNFaNeuropharmacologyIntroduction: Short-Chain Fatty Acids (SCFA) are products of intestinal microbial metabolism that can reach the brain and alter microglia in health and disease contexts. However, data are conflicting on the effect of acetate, the most abundant SCFA in the blood, in these cells. Objective: The authors aimed to investigate acetate as a modulator of the inflammatory response in microglia stimulated with LPS. Method: The authors used an immortalized cell line, C8-B4, and primary cells for in vitro treatments with acetate and LPS. Cell viability was analyzed by MTT, cytokine by RT-PCR, ELISA, and flow cytometry. The authors also performed in vivo and in silico analyses to study the role of acetate and the TNF-α contribution to the development of Experimental Autoimmune Encephalomyelitis (EAE). Results: Acetate co-administered with LPS was able to exacerbate the production of pro-inflammatory cytokines at gene and protein levels in cell lines and primary culture of microglia. However, the same effects were not observed when acetate was administered alone or as pretreatment, prior to the LPS stimulus. Additionally, pharmacological inhibition of histone deacetylase concomitantly with acetate and LPS led to decreased TNF-α production. In silico analysis showed a crucial role of the TNF-α pathway in EAE development. Moreover, acetate administration in vivo during the initial phase of EAE led to a better disease outcome and reduced TNF-α production. Conclusion: Treatment with acetate was able to promote the production of TNF-α in a concomitant LPS stimulus of microglia. However, the immune modulation of microglia by acetate pretreatment may be a component in the generation of future therapies for neurodegenerative diseases.Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo2022-06-29info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/clinics/article/view/21342010.1016/j.clinsp.2022.100062Clinics; Vol. 77 (2022); 100062Clinics; v. 77 (2022); 100062Clinics; Vol. 77 (2022); 1000621980-53221807-5932reponame:Clinicsinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/clinics/article/view/213420/195410Copyright (c) 2023 Clinicsinfo:eu-repo/semantics/openAccessFragas, Matheus GarciaOliveira, Daniel May deHiyane, Meire Ioshie Braga, Tarcio TeodoroCamara, Niels Olsen Saraiva2023-07-06T13:04:57Zoai:revistas.usp.br:article/213420Revistahttps://www.revistas.usp.br/clinicsPUBhttps://www.revistas.usp.br/clinics/oai||clinics@hc.fm.usp.br1980-53221807-5932opendoar:2023-07-06T13:04:57Clinics - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
The dual effect of acetate on microglial TNF-α production |
title |
The dual effect of acetate on microglial TNF-α production |
spellingShingle |
The dual effect of acetate on microglial TNF-α production Fragas, Matheus Garcia Acetate Microglia Inflammation Alzheimer Disease Encephalomyelitis TNFa Neuropharmacology |
title_short |
The dual effect of acetate on microglial TNF-α production |
title_full |
The dual effect of acetate on microglial TNF-α production |
title_fullStr |
The dual effect of acetate on microglial TNF-α production |
title_full_unstemmed |
The dual effect of acetate on microglial TNF-α production |
title_sort |
The dual effect of acetate on microglial TNF-α production |
author |
Fragas, Matheus Garcia |
author_facet |
Fragas, Matheus Garcia Oliveira, Daniel May de Hiyane, Meire Ioshie Braga, Tarcio Teodoro Camara, Niels Olsen Saraiva |
author_role |
author |
author2 |
Oliveira, Daniel May de Hiyane, Meire Ioshie Braga, Tarcio Teodoro Camara, Niels Olsen Saraiva |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Fragas, Matheus Garcia Oliveira, Daniel May de Hiyane, Meire Ioshie Braga, Tarcio Teodoro Camara, Niels Olsen Saraiva |
dc.subject.por.fl_str_mv |
Acetate Microglia Inflammation Alzheimer Disease Encephalomyelitis TNFa Neuropharmacology |
topic |
Acetate Microglia Inflammation Alzheimer Disease Encephalomyelitis TNFa Neuropharmacology |
description |
Introduction: Short-Chain Fatty Acids (SCFA) are products of intestinal microbial metabolism that can reach the brain and alter microglia in health and disease contexts. However, data are conflicting on the effect of acetate, the most abundant SCFA in the blood, in these cells. Objective: The authors aimed to investigate acetate as a modulator of the inflammatory response in microglia stimulated with LPS. Method: The authors used an immortalized cell line, C8-B4, and primary cells for in vitro treatments with acetate and LPS. Cell viability was analyzed by MTT, cytokine by RT-PCR, ELISA, and flow cytometry. The authors also performed in vivo and in silico analyses to study the role of acetate and the TNF-α contribution to the development of Experimental Autoimmune Encephalomyelitis (EAE). Results: Acetate co-administered with LPS was able to exacerbate the production of pro-inflammatory cytokines at gene and protein levels in cell lines and primary culture of microglia. However, the same effects were not observed when acetate was administered alone or as pretreatment, prior to the LPS stimulus. Additionally, pharmacological inhibition of histone deacetylase concomitantly with acetate and LPS led to decreased TNF-α production. In silico analysis showed a crucial role of the TNF-α pathway in EAE development. Moreover, acetate administration in vivo during the initial phase of EAE led to a better disease outcome and reduced TNF-α production. Conclusion: Treatment with acetate was able to promote the production of TNF-α in a concomitant LPS stimulus of microglia. However, the immune modulation of microglia by acetate pretreatment may be a component in the generation of future therapies for neurodegenerative diseases. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-06-29 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.revistas.usp.br/clinics/article/view/213420 10.1016/j.clinsp.2022.100062 |
url |
https://www.revistas.usp.br/clinics/article/view/213420 |
identifier_str_mv |
10.1016/j.clinsp.2022.100062 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://www.revistas.usp.br/clinics/article/view/213420/195410 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2023 Clinics info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2023 Clinics |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo |
publisher.none.fl_str_mv |
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo |
dc.source.none.fl_str_mv |
Clinics; Vol. 77 (2022); 100062 Clinics; v. 77 (2022); 100062 Clinics; Vol. 77 (2022); 100062 1980-5322 1807-5932 reponame:Clinics instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Clinics |
collection |
Clinics |
repository.name.fl_str_mv |
Clinics - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
||clinics@hc.fm.usp.br |
_version_ |
1800222766636466176 |