Ellagic acid and urolithin A modulate the immune response in LPS-stimulated U937 monocytic cells and THP-1 differentiated macrophages
| Autor: | Kjersti Aaby, Sissel Beate Rønning, Grethe Iren A. Borge, Vibeke Voldvik, Silje Kristine Bergum |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
THP-1 Cells 030309 nutrition & dietetics Metabolite Pharmacology Monocytes Protocatechuic acid 03 medical and health sciences chemistry.chemical_compound Ellagic Acid Coumarins medicine Animals Humans THP1 cell line 030304 developmental biology 0303 health sciences U937 cell Macrophages Monocyte Immunity NF-kappa B U937 Cells General Medicine Urolithin medicine.anatomical_structure chemistry Cytokines Cytokine secretion Signal Transduction Food Science Ellagic acid |
| Zdroj: | Food & Function |
| ISSN: | 2042-650X 2042-6496 |
| DOI: | 10.1039/c9fo03008e |
| Popis: | Dietary polyphenols are subjected, following ingestion, to an extensive metabolism, and the molecules that act at the cellular and tissue level will be, most likely, metabolites rather than native polyphenols. The mechanisms behind the positive effects exerted by polyphenols are not yet completely elucidated, since most in vitro studies use unmetabolised polyphenols rather than the metabolites present in the body. The aim of this study was to investigate and compare the potential effect of phenolic metabolites on the immune response using U937 monocyte and THP-1 macrophage cell cultures. Of the 16 metabolites tested, urolithins (Uro), and Uro A, in particular were the most potent, showing a modest increase in basal NF-κB activity and a reduction in lipopolysaccaride (LPS)-induced NF-κB activity, gene expression and secretion of pro-inflammatory cytokines. Protocatechuic acid and its sulfate/glucuronide metabolites reduced LPS-induced NF-κB activity, but not IL-6 and TNF-α cytokine secretion. Interestingly, both ellagic acid and its metabolite Uro A had immunomodulating effects, although they regulated the immune response differently, and both reduced LPS-induced NF-κB activity in U937 cells. However, while Uro A dramatically reduced IL-6 and IL-10 mRNA expression, no effect could be observed with ellagic acid. In THP-1 cells, treatment with ellagic acid dramatically reduced the expression of Toll-like receptor 4, while Uro A had no effect. The dual role observed for Uro A, showing both a modest increase in basal NF-κB activity and a reduction in LPS-induced NF-κB activity, as well as a reduction in LPS-induced pro-inflammatory cytokine secretion, makes this metabolite particularly interesting for further studies in animals and humans. |
| Databáze: | OpenAIRE |
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