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Citrus peel polymethoxyflavones nobiletin and tangeretin suppress LPS- and IgE-mediated activation of human intestinal mast cells
- Source :
- European journal of nutrition. 56(4)
- Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 14366215
- Volume :
- 56
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- European journal of nutrition
- Accession number :
- edsair.doi.dedup.....38a7a5bee184141f6879d2ef2534b372