Inhibition of serotonin transporter expression by C/EBPβ in LPS-activated macrophage cells (HD11)

Serotonin (5-hydroxytryptamine; 5-HT) transporter (5-HTT) is involved in inflammation and the stress response. In this study, we examined the regulation of 5-HTT expression in macrophage HD11 cells in response to bacterial LPS. Long-term exposure of cells to LPS (6–18 h) produced a decrease in 5-HTT...

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Bibliographic Details
Published in:Innate immunity (London, England) England), 2015-05, Vol.21 (4), p.406-415
Main Authors: Zimmermann, Katrin, van Phi, Valerie D, Brase, Angela, Phi-van, Loc
Format: Article
Language:English
Subjects:
Animals
Binding Sites - genetics
CCAAT-Binding Factor - genetics
CCAAT-Binding Factor - metabolism
Cell Line
Chickens
Down-Regulation - genetics
Lipopolysaccharides - immunology
Macrophages - immunology
Promoter Regions, Genetic - genetics
Protein Binding
RNA, Small Interfering - genetics
Serotonin Plasma Membrane Transport Proteins - genetics
Serotonin Plasma Membrane Transport Proteins - metabolism
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Summary:Serotonin (5-hydroxytryptamine; 5-HT) transporter (5-HTT) is involved in inflammation and the stress response. In this study, we examined the regulation of 5-HTT expression in macrophage HD11 cells in response to bacterial LPS. Long-term exposure of cells to LPS (6–18 h) produced a decrease in 5-HTT mRNA expression. Accordingly, reduced 5-HTT activity measured by 5-HT uptake was also observed in LPS-treated HD11 cells. Moreover, LPS treatment, as well as co-transfection with an expression vector encoding the chicken CCAAT/enhancer binding protein beta (C/EBPβ), resulted in inhibition of 5-HTT promoter activity. Indeed, sequence analysis revealed several C/EBPβ binding motifs in the upstream region of the 5-HTT gene, which specifically interacted with C/EBPβ both in an in vitro band shift assay and in living HD11 cells. The C/EBPβ binding was activated in cells treated with LPS. The role of C/EBPβ in LPS inhibition of 5-HTT expression was further confirmed by small interfering RNA interference, which demonstrated that knockdown of endogenous C/EBPβ attenuated the inhibition of 5-HTT expression in LPS-treated cells. Taken together, the results suggest that C/EBPβ plays a critical role in regulating the 5-HTT gene in macrophages in response to pro-inflammatory stimuli.
ISSN:1753-4259
1753-4267
DOI:10.1177/1753425914547434