title: Protocatechuic acid inhibits human dendritic cell functional activation: role of PPARγ up-modulation.
abstract: Polyphenols have been shown to exhibit anti-inflammatory, anti-oxidant and immunomodulatory activities. However, the effects of anthocyanins, flavonoids of great nutritional interest, in particular of their metabolite protocatechuic acid (PCA) on the phenotypic and functional maturation of human dendritic cells (DCs) are still largely unknown. In this study, we report that PCA is efficiently taken up and accumulated in human monocyte-derived DCs (MD-DCs). PCA exposure of MD-DCs markedly impaired the production of proinflammatory cytokines and chemokines (i.e. IL-6, IL-8 and CCL2) in response to bacterial endotoxin and leptin, and down-regulated the lipopolysaccharide (LPS)-induced migratory response of MD-DCs to CCL19. Conversely, the phenotypic profile induced by LPS-mediated activation as well as IL-12 production was not affected. Interestingly, we found that PPARγ is a main factor in the PCA-induced effects as blocking its activity abolish PCA capacity to down-regulate IL-6 and IL-8, but not CCL2, secretion and to inhibit MD-DC migration. In keeping with this observation, cytosol to nucleus translocation and PPARγ activity were found to be directly stimulated by PCA exposure of MD-DCs. These novel findings provide new insight into the immunoregulatory effects of polyphenol metabolites in DCs opening new perspectives on their potential application in the prevention of acute and chronic inflammatory diseases.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Del Cornò
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Varano
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Scazzocchio
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Carmelina
authors.initials: C
authors.lastname: Filesi
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Masella
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy. Electronic address: sandra.gessani@iss.it.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gessani
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001692:Biological Transport; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000276:immunology; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D020738:Leptin / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D047495:PPAR gamma / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D016588:Anticarcinogenic Agents; C515460:CCL19 protein, human; C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D054415:Chemokine CCL19; D018932:Chemokine CCL2; D062385:Hydroxybenzoates; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D020738:Leptin; D008070:Lipopolysaccharides; D047495:PPAR gamma; C009091:protocatechuic acid
keywords: Dendritic cells; Immunoregulation; PPARγ; Polyphenols; Protocatechuic acid