Galleggiante Vanessa, De Santis Stefania, Cavalcanti Elisabetta, Scarano Aurelia, De Benedictis Maria, Serino Grazia, Caruso Maria Lucia, Mastronardi Mauro, Pinto Aldo, Campiglia Pietro, Kunde Dale, Santino Angelo, Chieppa Marcello
National Institute of Gastroenterology "S. de Bellis", Institute of Research, Castellana Grotte (BA), Italy.
Institute of Sciences of Food Production C.N.R., Unit of Lecce, via Monteroni, 73100, Lecce, Italy.
Curr Pharm Des. 2017;23(14):2139-2146. doi: 10.2174/1381612823666170112125355.
Fruits and vegetables are rich in plant polyphenols, whose consumption is encouraged in healthy dietary regimes due to their antioxidants and anti-inflammatory effects. These organic molecules exhibit numerous properties including phylochelation; the ability to complex metal ions, including highly reactive iron. Among polyphenols, we focused our attention on quercetin that previously demonstrated its ability to reduce dendritic cells (DCs) inflammatory cytokine secretion and antigen presentation following LPS exposure. Dendritic cell inflammatory response is also associated with modulation of several iron metabolism related genes.
To characterize the axis between quercetin exposure and iron extracellular transport that may explain polyphenol anti-inflammatory abilities.
Bone marrow derived DCs were exposed to 25μM of quercetin on day 7 and treated with 1 μg/mL of LPS on day 8. The relation between quercetin exposure and the expression level of genes involved in iron homeostasis was addressed by qPCR. The axis between iron export and quercetin exposure was confirmed in vitro and in vivo using quercetin gavage and quercetin-enriched diet.
Here we demonstrate that DCs, exposed to quercetin, activate a pattern of genes that increase extracellular iron export, resulting in an overall decrease in the intracellular iron content and consequent diminished inflammatory abilities. This DCs phenotype is consistent with anti-inflammatory phenotype of the mucosal resident DCs, the ones most commonly exposed to polyphenols.
Iron balance is a crucial checkpoint for DCs inflammatory abilities. Quercetin-enriched nutritional regimes that favor DCs extracellular iron transport could reduce the incidence of chronic inflammatory syndromes.
水果和蔬菜富含植物多酚，由于其抗氧化和抗炎作用，在健康饮食中鼓励食用这些多酚。这些有机分子具有多种特性，包括植物螯合作用；即与金属离子络合的能力，包括高反应性铁离子。在多酚中，我们将注意力集中在槲皮素上，它先前已证明能够在脂多糖（LPS）暴露后降低树突状细胞（DCs）炎性细胞因子的分泌和抗原呈递。树突状细胞的炎症反应也与几种铁代谢相关基因的调节有关。
表征槲皮素暴露与铁细胞外转运之间的轴，这可能解释多酚的抗炎能力。
在第7天将骨髓来源的DCs暴露于25μM槲皮素，并在第8天用1μg/mL脂多糖处理。通过定量聚合酶链反应（qPCR）研究槲皮素暴露与铁稳态相关基因表达水平之间的关系。使用槲皮素灌胃和富含槲皮素的饮食在体外和体内证实了铁输出与槲皮素暴露之间的轴。
在此我们证明，暴露于槲皮素的DCs激活了一种增加细胞外铁输出的基因模式，导致细胞内铁含量总体下降，从而降低了炎症能力。这种DCs表型与黏膜驻留DCs的抗炎表型一致，黏膜驻留DCs是最常接触多酚的细胞。
铁平衡是DCs炎症能力的关键检查点。有利于DCs细胞外铁转运的富含槲皮素的营养方案可以降低慢性炎症综合征的发生率。
