• Matheus Garcia Fragas, Daniel May de Oliveira, Meire Ioshie Hiyane, Tarcio Teodoro Braga, and CamaraNiels Olsen SaraivaNOSDepartment of Immunology, Instituto de Ciências Biomédicas (ICB IV), Universidade de São Paulo, São Paulo, SP, Brazil; Nephrology Division, Universidade Federal de São Paulo, São Paulo, SP, Brazil..
• Department of Immunology, Instituto de Ciências Biomédicas (ICB IV), Universidade de São Paulo, São Paulo, SP, Brazil.
• Clinics (Sao Paulo). 2022 Jan 1; 77: 100062.

IntroductionShort-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.ObjectiveThe authors aimed to investigate acetate as a modulator of the inflammatory response in microglia stimulated with LPS.MethodThe 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).ResultsAcetate 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.ConclusionTreatment 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.Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.

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