Abstract
Mast cells are central players in immediate-type hypersensitvity and inflammatory responses. In the present study, the effects of britanin on the passive cutaneous anaphylaxis (PCA) reaction in mice and on the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced production of pro-inflammatory cytokines in human mast cell line (HMC-1) were evaluated. The oral administration of britanin (10-20 mg/kg) decreased the mast cell-mediated PCA reaction in IgE-sensitized mice. In the activity and mechanism of britanin in vitro assay, britanin suppressed the gene expression and secretion of pro-inflammatory cytokines in a dose-dependent manner in HMC-1. In addition, britanin attenuated PMACI-induced activation of NF-κB as indicated by the inhibition of the degradation of IκBα, nuclear translocation of NF-κB, NF-κB/DNA binding activity assay, and blocked the phosphorylation of p38 MAP kinase, in a dose-dependent manner. We conclude that britanin may have potential as a treatment for allergic-inflammatory diseases.
Keywords:
Britanin; Mast Cells; Mitogen-Activated Protein (MAP) Kinases; Nuclear Factor (NF)-κB; Passive Cutaneous Anaphylaxis (PCA); Pro-Inflammatory Cytokines.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Ophthalmic
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Animals
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Calcimycin / pharmacology
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Calcium Ionophores / pharmacology
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Cells, Cultured
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Cytokines / metabolism
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Dose-Response Relationship, Drug
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Humans
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Hypersensitivity, Immediate / drug therapy*
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Hypersensitivity, Immediate / immunology*
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Inflammation / drug therapy*
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Inflammation / immunology*
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Inflammation Mediators / metabolism
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Inula / chemistry*
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Lactones / administration & dosage
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Lactones / isolation & purification
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Lactones / pharmacology*
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Male
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Mast Cells / metabolism*
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Mice, Inbred ICR
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NF-kappa B / metabolism
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Passive Cutaneous Anaphylaxis / drug effects*
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Passive Cutaneous Anaphylaxis / immunology
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Phosphorylation / drug effects
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Phytotherapy*
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Sesquiterpenes / administration & dosage
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Sesquiterpenes / isolation & purification
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Sesquiterpenes / pharmacology*
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Tetradecanoylphorbol Acetate / analogs & derivatives
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Tetradecanoylphorbol Acetate / pharmacology
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Calcium Ionophores
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Cytokines
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Inflammation Mediators
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Lactones
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NF-kappa B
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Sesquiterpenes
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britannin
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Calcimycin
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phorbolol myristate acetate
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p38 Mitogen-Activated Protein Kinases
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Tetradecanoylphorbol Acetate