Phenolic compounds of red wine aglianico del vulture modulate the functional activity of macrophages via inhibition of NF-κB and the citrate pathway

• Autor(a) principal: Santarsiero, Anna
• Data de Publicação: 2021
• Outros Autores: Convertini, Paolo, Vassallo, Antonio, Santoro, Valentina, Todisco, Simona, Iacobazzi, Dominga, Fondufe-Mittendorf, Yvonne, Martelli, Giuseppe, Oliveira, Marcos Roberto de, Montanaro, Rosangela, Brancaleone, Vincenzo, Stöckl, Johannes, Infantino, Vittoria
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/230964
• topic: Vinho; Compostos fenólicos; NF-kappa B; Ácido cítrico; Macrófagos

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.