Impact of polyphenols on mast cells with special emphasis on the effect of quercetin and luteolin.

Polyphenols are ubiquitous in food and have long been recognized to possess antioxidant, anti-inflammatory and anticancer activities. Mast cells (MCs) are implicated in the pathogenesis of inflammatory diseases, allergy, autoimmunity and cancer. MCs derive from hematopoietic progenitor cells, reside virtually in all vascularized tissue and are activated by crosslinking of FceRI-bound IgE (at very high affinity: 1 × 1010 M-1) with multivalent antigen. MCs in cytoplasmic granules release preformed chemical mediators, and also they can release lipid mediators and cytokines/chemokines without degranulation. Luteolin, 3',4',5,7-tetrahydroxyflavone, is a flavonoid contained in many kinds of plants including vegetables and fruits. This anti-oxidant product inhibits interleukin (IL)-6, IL-8 and vascular endothelial growth factor (VEGF) production from tumor necrosis factor (TNF)-triggered keratinocytes, and is a candidate for use in alternative therapies in the treatment of inflammatory skin disorders. Quercetin (3,3',4',5,7-pentahydroxyflavone) is a ubiquitous flavonoid which exhibits anti-cancer, anti-oxidative and anti-inflammatory properties and causes a reduction in the availability of nitrite that influences vascular function. Quercetin exerts physiological functions though the interaction with phosphatidylinositol-3-phosphate kinase (PI3K), mitogen-activated protein kinase (MAPK), extracellular signal regulated kinase (ERK), kinase (MEK) 1, and others, and has a negative effect on FceRI cross-linking and other activating receptors on mast cells. In this article we report for the first time the interrelationship between mast cells and polyphenols.

Expression and secretion of CXCL8 (IL-8), release of tryptase and transcription of histidine decarboxylase mRNA by anti-IgE-activated human umbilical cord blood-derived cultured mast cells.

Activation of cytokine receptors and alterations in cytokines are thought to play important roles in neuronal dysfunction and in the pathogenesis of the nervous system diseases. CXCL8 (IL-8) is a CXC chemokine with chemotactic and inflammatory properties. Chemokines control mast cell infiltration in several inflammatory diseases, including stress and neurological dysfunctions. Using isolated human umbilical cord blood-derived cultured mast cells (HUCMC) from hematopoietic stem cells CD34+, mast cells were immunologically activated with anti-IgE at concentrations of 1, 5, 10 and 20 microg/ml leading to the dose-dependent production of IL-8 (p < 0.05). The increase in IL-8 mRNA expression was also noted when the cells were treated with anti-IgE at 10 microg/ml for 6 h. Immunologically activated HUCMC provoked the generation of tryptase in a dose- and time-dependent manner. We also found increased histidine decarboxylase (HDC) expression in activated HUCMC after 6 h of incubation, a rate-limiting enzyme responsible for the generation of histamine from histidine. Taken together, these results confirm that anti-IgE-activated mast cells release inflammatory mediators including CXCL8, a CXC chemokine which regulates several biological effects of mast cells, e.g. chemoattraction, and possibly causes cell arrest.