Inhibitory effects of fluoxetine on the secretion of inflammatory mediators and JAK/STAT3 and JNK/TLR4 gene expression.
Mol Biol Rep
; 50(3): 2231-2241, 2023 Mar.
Article
em En
| MEDLINE
| ID: mdl-36571654
ABSTRACT
BACKGROUND:
Selective serotonin reuptake inhibitors (SSRIs) are the most common class of medicines used for the treatment of major depression. Recent studies have reported an association between depression and inflammation and suggested the significant effects of SSRIs on inflammatory processes.METHODS:
The current study aimed to evaluate the effects of fluoxetine, an SSRI, on the level of inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in the rat serum and RAW264.7 mouse macrophage cell line, using ELISA sandwich assays. Also, the expression of inflammatory genes, including JAK/STAT3 and TLR4/JNK, was examined in macrophages, using real-time quantitative reverse transcription PCR to determine the potential mechanism of fluoxetine in inflammation. The rats received fluoxetine (10, 20, and 40 mg/kg) 30 min before lipopolysaccharide (LPS) treatment for 90 min. The cells received different doses of fluoxetine (5, 10, and 20 µg/mL) before stimulation with LPS for 24 or 48 h.RESULTS:
The serum concentrations of IL-1ß, IL-6, and TNF-α were reduced in rats and cells treated with fluoxetine. Following fluoxetine administration, the expression of JAK/STAT3 and TLR4/JNK genes was significantly decreased in the RAW264.7 cells treated with LPS for 24 h. However, after 48 h of treatment with LPS, fluoxetine failed to diminish the elevated expression of JAK and JNK genes, while it significantly decreased the expression of STAT3 and TLR4 genes.CONCLUSION:
The findings revealed that fluoxetine has anti-inflammatory properties, mainly due to the reduction of inflammatory cytokines and inhibition of JAK/STAT3 and TLR4/JNK gene expression in macrophages.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fluoxetina
/
Fator de Necrose Tumoral alfa
Limite:
Animals
Idioma:
En
Revista:
Mol Biol Rep
Ano de publicação:
2023
Tipo de documento:
Article