Phenolic Compounds of Red Wine Aglianico del Vulture Modulate the Functional Activity of Macrophages via Inhibition of NF-κB and the Citrate Pathway

Anna Santarsiero, Paolo Convertini, Antonio Vassallo, Valentina Santoro, Simona Todisco, Dominga Iacobazzi, Yvonne Fondufe-Mittendorf, Giuseppe Martelli, Marcos R. De Oliveira, Rosangela Montanaro, Vincenzo Brancaleone, Johannes Stöckl, Vittoria Infantino

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Phenolic compounds of red wine powder (RWP) extracted from the Italian red wine Aglianico del Vulture have been investigated for the potential immunomodulatory and anti-inflammatory capacity on human macrophages. These compounds reduce the secretion of IL-1β, IL-6, and TNF-α proinflammatory cytokines and increase the release of IL-10 anti-inflammatory cytokine induced by lipopolysaccharide (LPS). In addition, RWP restores Annexin A1 levels, thus involving activation of proresolutive pathways. Noteworthy, RWP lowers NF-κB protein levels, promoter activity, and nuclear translocation. As a consequence of NF-κB inhibition, reduced promoter activities of SLC25A1 - encoding the mitochondrial citrate carrier (CIC) - and ATP citrate lyase (ACLY) metabolic genes have been observed. CIC, ACLY, and citrate are components of the citrate pathway: in LPS-activated macrophages, the mitochondrial citrate is exported by CIC into the cytosol where it is cleaved by ACLY in oxaloacetate and acetyl-CoA, precursors for ROS, NO⋅, and PGE2 inflammatory mediators. We identify the citrate pathway as a RWP target in carrying out its anti-inflammatory activity since RWP reduces CIC and ACLY protein levels, ACLY enzymatic activity, the cytosolic citrate concentration, and in turn ROS, NO⋅, PGE2, and histone acetylation levels. Overall findings suggest that RWP potentially restores macrophage homeostasis by suppressing inflammatory pathways and activating proresolutive processes.

Original languageEnglish
Article number5533793
JournalOxidative Medicine and Cellular Longevity
Volume2021
DOIs
StatePublished - 2021

Bibliographical note

Publisher Copyright:
© 2021 Anna Santarsiero et al.

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Cell Biology

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