Quercetin-Induced miR-369-3p Suppresses Chronic Inflammatory Response Targeting C/EBP-β

Vanessa Galleggiante, Stefania De Santis, Marina Liso, Giulio Verna, Eduardo Sommella, Mauro Mastronardi, Pietro Campiglia, Marcello Chieppa, Grazia Serino

Research output: Contribution to journalArticle

Abstract

SCOPE: Dendritic cells (DCs) are the most potent antigen-presenting cells that play an important role in the crosstalk between the innate and the adaptive immune response. Quercetin exposure is identified as an effective strategy to suppress the inflammatory response induced by LPS.

METHODS AND RESULTS: In this study, using a next-generation sequencing analysis, the effect of quercetin on microRNAs (miRNAs) expression in DCs is examined. A signature of 113 miRNAs that are differentially regulated in LPS-stimulated DCs after quercetin exposure is defined. It is demonstrated that the loss of function of miR-369-3p in LPS-stimulated DCs during quercetin exposure led to an increase of CCAAT/enhancer binding protein β (C/EBP-β) mRNA and protein and its downstream targets tumor necrosis factor-α (TNF-α) and interleukin 6 (IL6). Conversely, it is shown that the ectopic induction of miR-369-3p without quercetin suppresses the inflammatory response of LPS reducing C/EBP-β, TNF-α, and IL6 production. In vivo, oral administration of quercetin in dextran-sulfate-sodium-induced colitis induces miR-369-3p expression.

CONCLUSIONS: These findings indicate that quercetin-induced miR-369-3p regulates the inflammatory cascade in chronic inflammatory response and present promising therapeutic implications.

Original languageEnglish
Pages (from-to)e1801390
Number of pages13
JournalMolecular Nutrition and Food Research
DOIs
Publication statusE-pub ahead of print - Jul 23 2019

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CCAAT-Enhancer-Binding Proteins
Quercetin
quercetin
binding proteins
inflammation
dendritic cells
Dendritic Cells
tumor necrosis factors
MicroRNAs
microRNA
interleukin-6
Interleukin-6
Tumor Necrosis Factor-alpha
Dextran Sulfate
sodium sulfate
antigen-presenting cells
colitis
Adaptive Immunity
dextran
Antigen-Presenting Cells

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Quercetin-Induced miR-369-3p Suppresses Chronic Inflammatory Response Targeting C/EBP-β. / Galleggiante, Vanessa; De Santis, Stefania; Liso, Marina; Verna, Giulio; Sommella, Eduardo; Mastronardi, Mauro; Campiglia, Pietro; Chieppa, Marcello; Serino, Grazia.

In: Molecular Nutrition and Food Research, 23.07.2019, p. e1801390.

Research output: Contribution to journalArticle

Galleggiante, Vanessa ; De Santis, Stefania ; Liso, Marina ; Verna, Giulio ; Sommella, Eduardo ; Mastronardi, Mauro ; Campiglia, Pietro ; Chieppa, Marcello ; Serino, Grazia. / Quercetin-Induced miR-369-3p Suppresses Chronic Inflammatory Response Targeting C/EBP-β. In: Molecular Nutrition and Food Research. 2019 ; pp. e1801390.
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AU - Galleggiante, Vanessa

AU - De Santis, Stefania

AU - Liso, Marina

AU - Verna, Giulio

AU - Sommella, Eduardo

AU - Mastronardi, Mauro

AU - Campiglia, Pietro

AU - Chieppa, Marcello

AU - Serino, Grazia

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N2 - SCOPE: Dendritic cells (DCs) are the most potent antigen-presenting cells that play an important role in the crosstalk between the innate and the adaptive immune response. Quercetin exposure is identified as an effective strategy to suppress the inflammatory response induced by LPS.METHODS AND RESULTS: In this study, using a next-generation sequencing analysis, the effect of quercetin on microRNAs (miRNAs) expression in DCs is examined. A signature of 113 miRNAs that are differentially regulated in LPS-stimulated DCs after quercetin exposure is defined. It is demonstrated that the loss of function of miR-369-3p in LPS-stimulated DCs during quercetin exposure led to an increase of CCAAT/enhancer binding protein β (C/EBP-β) mRNA and protein and its downstream targets tumor necrosis factor-α (TNF-α) and interleukin 6 (IL6). Conversely, it is shown that the ectopic induction of miR-369-3p without quercetin suppresses the inflammatory response of LPS reducing C/EBP-β, TNF-α, and IL6 production. In vivo, oral administration of quercetin in dextran-sulfate-sodium-induced colitis induces miR-369-3p expression.CONCLUSIONS: These findings indicate that quercetin-induced miR-369-3p regulates the inflammatory cascade in chronic inflammatory response and present promising therapeutic implications.

AB - SCOPE: Dendritic cells (DCs) are the most potent antigen-presenting cells that play an important role in the crosstalk between the innate and the adaptive immune response. Quercetin exposure is identified as an effective strategy to suppress the inflammatory response induced by LPS.METHODS AND RESULTS: In this study, using a next-generation sequencing analysis, the effect of quercetin on microRNAs (miRNAs) expression in DCs is examined. A signature of 113 miRNAs that are differentially regulated in LPS-stimulated DCs after quercetin exposure is defined. It is demonstrated that the loss of function of miR-369-3p in LPS-stimulated DCs during quercetin exposure led to an increase of CCAAT/enhancer binding protein β (C/EBP-β) mRNA and protein and its downstream targets tumor necrosis factor-α (TNF-α) and interleukin 6 (IL6). Conversely, it is shown that the ectopic induction of miR-369-3p without quercetin suppresses the inflammatory response of LPS reducing C/EBP-β, TNF-α, and IL6 production. In vivo, oral administration of quercetin in dextran-sulfate-sodium-induced colitis induces miR-369-3p expression.CONCLUSIONS: These findings indicate that quercetin-induced miR-369-3p regulates the inflammatory cascade in chronic inflammatory response and present promising therapeutic implications.

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