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.
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This research was supported by FSC European funds (grant number C31G19000020002) and Ministry of Education, University and Research (MIUR) PRIN (grant number 2017NKB2N4_004).
The data used to support the findings of this study are available from the corresponding author upon request.
Santarsiero, Anna; Convertini, Paolo; Vassallo, Antonio; Santoro, Valentina; Todisco, Simona; Iacobazzi, Dominga; Fondufe-Mittendorf, Yvonne N.; Martelli, Giuseppe; de Oliveira, Marcos R.; Montanaro, Rosangela; Brancaleone, Vincenzo; Stöckl, Johannes; and Infantino, Vittoria, "Phenolic Compounds of Red Wine Aglianico del Vulture Modulate the Functional Activity of Macrophages via Inhibition of NF-κB and the Citrate Pathway" (2021). Molecular and Cellular Biochemistry Faculty Publications. 189.