Citrus peel polymethoxyflavones nobiletin and tangeretin suppress LPS- and IgE-mediated activation of human intestinal mast cells
Autor: | Katharina Feilhauer, Stephan C. Bischoff, Michael W. Schäffer, Axel Lorentz, Yvonne Hagenlocher |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Lipopolysaccharides Citrus Anti-Inflammatory Agents Medicine (miscellaneous) Stimulation CCL2 Pharmacology Nobiletin Proinflammatory cytokine 03 medical and health sciences Tangeretin chemistry.chemical_compound Medicine Humans Interleukin 8 Mast Cells Intestinal Mucosa Phosphorylation Cells Cultured Flavonoids Nutrition and Dietetics business.industry Plant Extracts Degranulation NF-kappa B Immunoglobulin E Flavones beta-N-Acetylhexosaminidases Intestines 030104 developmental biology Biochemistry chemistry Cytokines Tumor necrosis factor alpha Mitogen-Activated Protein Kinases business |
Zdroj: | European journal of nutrition. 56(4) |
ISSN: | 1436-6215 |
Popis: | Allergic diseases with mast cells (MC) as main effector cells show an increased prevalence. MC also play an essential role in other inflammatory conditions. Therapeutical use of anti-inflammatory nutraceuticals directly targeting MC activation could be of interest for afflicted patients. Nobiletin and tangeretin are citrus peel polymethoxyflavones, a group of citrus flavonoids, possessing anticancer, antimetastatic, and anti-inflammatory activities. Here, we analyzed the effects of nobiletin/tangeretin on LPS- and IgE-mediated stimulation of human intestinal mast cells (hiMC). MC isolated from human intestinal tissue were treated with different concentrations of nobiletin or tangeretin prior to stimulation via LPS/sCD14 or IgE-dependently. Degranulation, pro-inflammatory cytokine expression and phosphorylation of ERK1/2 were examined. Expression of CXCL8, CCL3, CCL4 and IL-1β in response to LPS-mediated stimulation was inhibited by nobiletin/tangeretin. hiMC activated IgE-dependently showed a reduced release of β-hexosaminidase and cysteinyl LTC4 in response to nobiletin, but not in response to tangeretin. Expression of CXCL8, CCL2, CCL3, CCL4 and TNF in IgE-dependently activated hiMC was decreased in a dose-dependent manner following treatment with nobiletin/tangeretin. IL-1β expression was only reduced by tangeretin. Compared to treatment with NF-κB inhibitor BMS345541 or MEK-inhibitor PD98059, nobiletin and tangeretin showed similar effects on mediator production. Phosphorylation of ERK1/2 upon IgE-mediated antigen stimulation was significantly suppressed by nobiletin and tangeretin. Nobiletin and, to a lesser extent, tangeretin could be considered as anti-inflammatory nutraceuticals by reducing release and production of proinflammatory mediators in MC. |
Databáze: | OpenAIRE |
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