PMID- 32832941
OWN - NLM
STAT- MEDLINE
DCOM- 20210506
LR  - 20210506
IS  - 2042-650X (Electronic)
IS  - 2042-6496 (Linking)
VI  - 11
IP  - 9
DP  - 2020 Sep 23
TI  - Ellagic acid and urolithin A modulate the immune response in LPS-stimulated U937 
      monocytic cells and THP-1 differentiated macrophages.
PG  - 7946-7959
LID - 10.1039/c9fo03008e [doi]
AB  - 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-kappaB activity and a reduction in lipopolysaccaride 
      (LPS)-induced NF-kappaB activity, gene expression and secretion of pro-inflammatory 
      cytokines. Protocatechuic acid and its sulfate/glucuronide metabolites reduced 
      LPS-induced NF-kappaB activity, but not IL-6 and TNF-alpha 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-kappaB 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-kappaB 
      activity and a reduction in LPS-induced NF-kappaB 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.
FAU - Ronning, Sissel Beate
AU  - Ronning SB
AUID- ORCID: 0000-0002-2255-0172
AD  - Nofima AS, Osloveien 1, 1433 AS, Norway. sissel.ronning@nofima.no.
FAU - Voldvik, Vibeke
AU  - Voldvik V
AD  - Nofima AS, Osloveien 1, 1433 AS, Norway. sissel.ronning@nofima.no.
FAU - Bergum, Silje Kristine
AU  - Bergum SK
AD  - Nofima AS, Osloveien 1, 1433 AS, Norway. sissel.ronning@nofima.no.
FAU - Aaby, Kjersti
AU  - Aaby K
AUID- ORCID: 0000-0002-5853-9901
AD  - Nofima AS, Osloveien 1, 1433 AS, Norway. sissel.ronning@nofima.no.
FAU - Borge, Grethe Iren A
AU  - Borge GIA
AUID- ORCID: 0000-0003-0086-4434
AD  - Nofima AS, Osloveien 1, 1433 AS, Norway. sissel.ronning@nofima.no.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Food Funct
JT  - Food & function
JID - 101549033
RN  - 0 (Coumarins)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 1143-70-0 (3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one)
RN  - 19YRN3ZS9P (Ellagic Acid)
SB  - IM
MH  - Animals
MH  - Coumarins/*pharmacology
MH  - Cytokines/metabolism
MH  - Ellagic Acid/*pharmacology
MH  - Humans
MH  - Immunity/*drug effects
MH  - Lipopolysaccharides/*adverse effects
MH  - Macrophages/*drug effects
MH  - Monocytes/*drug effects
MH  - NF-kappa B/metabolism
MH  - Signal Transduction/drug effects
MH  - THP-1 Cells
MH  - U937 Cells
EDAT- 2020/08/25 06:00
MHDA- 2021/05/07 06:00
CRDT- 2020/08/25 06:00
PHST- 2020/08/25 06:00 [pubmed]
PHST- 2021/05/07 06:00 [medline]
PHST- 2020/08/25 06:00 [entrez]
AID - 10.1039/c9fo03008e [doi]
PST - ppublish
SO  - Food Funct. 2020 Sep 23;11(9):7946-7959. doi: 10.1039/c9fo03008e.