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, 22 (1), 27-34

Curcumin Inhibits the Activation of Immunoglobulin E-Mediated Mast Cells and Passive Systemic Anaphylaxis in Mice by Reducing Serum Eicosanoid and Histamine Levels

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Curcumin Inhibits the Activation of Immunoglobulin E-Mediated Mast Cells and Passive Systemic Anaphylaxis in Mice by Reducing Serum Eicosanoid and Histamine Levels

Xian Li et al. Biomol Ther (Seoul).

Abstract

Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2) and 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular Ca(2+) influx via phospholipase Cγ1 (PLCγ1) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-κB (NF-κB) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum LTC4, PGD2, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.

Keywords: Curcumin; Leukotriene C4; Mast cell; Mitogen activated protein kinase; Passive systemic anaphylaxis; Prostaglandin D2.

Figures

Fig. 1.
Fig. 1.
Curcumin inhibited IgE/Ag-induced PSA reaction. In the PSA test, ICR mice were sensitized by injecting 2 μg of IgE i.v. in 100 μl saline or injected with saline alone. 24 h later mice were administered 25 or 50 mg/kg of curcumin or 50 mg/kg fexofenadine-HCl (Fexo) and 1 h later were challenged with 4 mg of DNP-HSA i.v in 200 μl saline; blood was collected by cardiac puncture 5 min after the Ag challenge. The concentration of serum LTC4 (A), PGD2 (B), and histamine (C) were determined using appropriate enzyme immunoassay kits (Cayman Chemicals). The values indicate the mean ± S.D. from three independent experiments, **p<0.01 versus IgE/Ag sensitized mice). Fexo (50 mg/kg) was used as an anti-histamine control drug.
Fig. 2.
Fig. 2.
Effect of Curcumin on LTC4 generation and on Ca2+ mobilization in IgE/Ag-activated BMMCs. IgE-sensitized BMMCs were pre-incubated with the indicated concentration of curcumin or Bay61-3606 for 1 h and then stimulated with DNP-HSA for 15 min. LTC4 released into the supernatant was quantified using an enzyme immunoassay kit (A). Relative intracellular Ca2+ levels were determined (at 5 min) (B). *p<0.05, **p<0.01 and ***p<0.001 versus the IgE/Ag-treated group. Results are the averages of three independent experiments.
Fig. 3.
Fig. 3.
Effects of curcumin and Bay 61-3606 on cPLA2α and 5-LO translocation and MAPKs activation. IgE-sensitized BMMCs were pre-incubated for 1 h with the indicated concentrations of curcumin or Bay 61-3606 and then stimulated with DNP-HSA for 15 min. Cytosolic and nuclear fractions were immunoblotted with antibodies for phospho-cPLA2α (Ser505) and 5-LO (A), and cell lysates were immunoblotted for the total and phosphorylated forms of ERK1/2, JNK and p38 (B). Immunoblots of β-actin and lamin B were used as controls for cytosol and nuclear fractions, respectively.
Fig. 4.
Fig. 4.
Effect of Curcumin on COX-2 dependent PGD2 generation and on Akt-NF-κB activation. IgE-sensitized BMMCs were pre-incubated with the indicated concentration of curcumin or Bay61-3606 for 1 h and then stimulated with DNP-HSA for 7 h. PGD2 released into the supernatant was quantified using an enzyme immunoassay kit and the cells were used for immunoblotting of COX-2 protein (A). IgE-sensitized BMMCs were pre-incubated with curcumin or Bay 61-3606 for 1 h and stimulated with DNP-HSA for 15 min. Then cells were taken for the immunoblot detection of Akt, IKK, IκBα cytosolic NF-κB (p65), nuclear NF-κB (p65), β-actin and lamin B. Nuclear extracts were used for the NF-κB (p65) immunoblot. Results are presented as mean ± S.D. of three independent experiments. **p<0.01 versus the IgE/Ag-treated group.
Fig. 5.
Fig. 5.
Effect of curcumin on the Syk pathway. IgE-sensitized BMMCs were preincubated with curcumin or Bay 61-3606 for 1 h, and then stimulated with DNP-HSA for 5 min. Cell lysates were subjected to immunoprecipitation and immunoblot analysis for the phosphorylated forms of Syk, LAT and PLCγ1. Bay 61-3606 was used as a positive control with respect to the suppression of the Syk-mediated pathway. The relative ratios of p-Syk/Syk, p-LAT/LAT and p-PLCγ1/PLCγ1 protein levels were determined by measuring immunoblot band intensities by scanning densitometry (**p<0.01 and ***p<0.001). The results shown are representative of three independent experiments.

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