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Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells.

Jeong KT, Lee E, Park NY, Kim SG, Park HH, Lee J, Lee YJ, Lee E - Biomol Ther (Seoul) (2015)

Bottom Line: Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC.To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC.Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cγ1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-κB pathways in BMMC.

View Article: PubMed Central - PubMed

Affiliation: Research and Development Division, Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-210.

ABSTRACT
Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cγ1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-κB pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

No MeSH data available.


Related in: MedlinePlus

Suppressive effect of imperatorin on activation of MAPKs. BMMC sensitized overnight with IgE were pre-incubated with the indicated concentrations of imperatorin for 1 h and stimulated with DNP-HAS (Ag, 100 mg/ml) for 15 min. The cells were harvested and cell lysates were prepared for measurement of total or phosphorylated ERK1/2 (A), JNK (B), and p38 (C) by Western blot analysis. Results are representative of three separate experiments. The values are expressed as the means ± S.E.M. of three different samples. **p<0.01, ***p<0.001, significantly different from the control as determined by one-way ANOVA.
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f4-bt-23-421: Suppressive effect of imperatorin on activation of MAPKs. BMMC sensitized overnight with IgE were pre-incubated with the indicated concentrations of imperatorin for 1 h and stimulated with DNP-HAS (Ag, 100 mg/ml) for 15 min. The cells were harvested and cell lysates were prepared for measurement of total or phosphorylated ERK1/2 (A), JNK (B), and p38 (C) by Western blot analysis. Results are representative of three separate experiments. The values are expressed as the means ± S.E.M. of three different samples. **p<0.01, ***p<0.001, significantly different from the control as determined by one-way ANOVA.

Mentions: The phosphorylation and activation of MAPKs are crucial for NF-κB and the subsequent activation of inflammatory mediators (Kaminska, 2005). In addition, cPLA2 activity and COX-2-dependent PGD2 generation are increased by phosphorylation of MAPKs (Lin et al., 1993; Lu et al., 2011). Therefore, we examined the effect of imperatorin on phosphorylation of MAPKs in IgE-sensitized BMMC. BMMC were pre-treated with imperatorin and inhibitors of MAPKs for 1 h before stimulation with Ag. As shown in Fig. 4, Ag stimulation in IgE-sensitized BMMC induced the expression of JNK, ERK1/2, and p38 without altering total protein levels and imperatorin suppressed the phosphorylation of all three MAPKs. The specific inhibitors of MAPKs (SB203580, SP600125, and PD98059) inhibited the phosphorylations of their respective MAPKs.


Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells.

Jeong KT, Lee E, Park NY, Kim SG, Park HH, Lee J, Lee YJ, Lee E - Biomol Ther (Seoul) (2015)

Suppressive effect of imperatorin on activation of MAPKs. BMMC sensitized overnight with IgE were pre-incubated with the indicated concentrations of imperatorin for 1 h and stimulated with DNP-HAS (Ag, 100 mg/ml) for 15 min. The cells were harvested and cell lysates were prepared for measurement of total or phosphorylated ERK1/2 (A), JNK (B), and p38 (C) by Western blot analysis. Results are representative of three separate experiments. The values are expressed as the means ± S.E.M. of three different samples. **p<0.01, ***p<0.001, significantly different from the control as determined by one-way ANOVA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556201&req=5

f4-bt-23-421: Suppressive effect of imperatorin on activation of MAPKs. BMMC sensitized overnight with IgE were pre-incubated with the indicated concentrations of imperatorin for 1 h and stimulated with DNP-HAS (Ag, 100 mg/ml) for 15 min. The cells were harvested and cell lysates were prepared for measurement of total or phosphorylated ERK1/2 (A), JNK (B), and p38 (C) by Western blot analysis. Results are representative of three separate experiments. The values are expressed as the means ± S.E.M. of three different samples. **p<0.01, ***p<0.001, significantly different from the control as determined by one-way ANOVA.
Mentions: The phosphorylation and activation of MAPKs are crucial for NF-κB and the subsequent activation of inflammatory mediators (Kaminska, 2005). In addition, cPLA2 activity and COX-2-dependent PGD2 generation are increased by phosphorylation of MAPKs (Lin et al., 1993; Lu et al., 2011). Therefore, we examined the effect of imperatorin on phosphorylation of MAPKs in IgE-sensitized BMMC. BMMC were pre-treated with imperatorin and inhibitors of MAPKs for 1 h before stimulation with Ag. As shown in Fig. 4, Ag stimulation in IgE-sensitized BMMC induced the expression of JNK, ERK1/2, and p38 without altering total protein levels and imperatorin suppressed the phosphorylation of all three MAPKs. The specific inhibitors of MAPKs (SB203580, SP600125, and PD98059) inhibited the phosphorylations of their respective MAPKs.

Bottom Line: Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC.To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC.Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cγ1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-κB pathways in BMMC.

View Article: PubMed Central - PubMed

Affiliation: Research and Development Division, Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-210.

ABSTRACT
Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cγ1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-κB pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

No MeSH data available.


Related in: MedlinePlus