ABSTRACT
BACKGROUND: The aim of this study was to evaluate the inhibitory effect of tamarixetin on the production of inflammatory mediators in IgE/antigen-induced mouse bone marrow-derived mast cells (BMMCs). MATERIALS AND METHODS: The effects of tamarixetin on mast cell activation were investigated with regard to degranulation, eicosanoid generation, Ca2+ influx, and immunoblotting of various signaling molecules. RESULTS: Tamarixetin effectively decreased degranulation and the eicosanoid generation such as leukotriene C4 and prostaglandin D2 in BMMCs. To elucidate the mechanism involved, we investigated the effect of tamarixetin on the phosphorylation of signal molecules. Tamarixetin inhibited the phosphorylation of Akt and its downstream signal molecules including IKK and nuclear factor κB. In addition, tamarixetin downregulated the phosphorylation of cytosolic phospholipase A2 (cPLA2) and p38 mitogen-activated protein kinase. CONCLUSIONS: Taken together, this study suggests that tamarixetin inhibits degranulation and eicosanoid generation through the PLCγ1 as well as Akt pathways in BMMCs, which would be potential for the prevention of allergic inflammatory diseases.
Subject(s)
Cell Degranulation/drug effects , Disaccharides/pharmacology , Eicosanoids/biosynthesis , Inflammation Mediators/metabolism , Inula/chemistry , Mast Cells/drug effects , Quercetin/analogs & derivatives , Animals , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Calcium/metabolism , Leukotriene C4/biosynthesis , Mast Cells/metabolism , Mast Cells/physiology , Mice , Mice, Inbred BALB C , NF-kappa B/metabolism , Phospholipase C gamma/metabolism , Phospholipases A2/metabolism , Phosphorylation/drug effects , Prostaglandin D2/biosynthesis , Protein Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Quercetin/pharmacology , beta-N-Acetylhexosaminidases/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Background: The aim of this study was to evaluate the inhibitory effect of tamarixetin on the production of inflammatory mediators in IgE/antigen-induced mouse bone marrow-derived mast cells (BMMCs). Materials and methods: The effects of tamarixetin on mast cell activation were investigated with regard to degranulation, eicosanoid generation, Ca2+ influx, and immunoblotting of various signaling molecules. Results: Tamarixetin effectively decreased degranulation and the eicosanoid generation such as leukotriene C4 and prostaglandin D2 in BMMCs. To elucidate the mechanism involved, we investigated the effect of tamarixetin on the phosphorylation of signal molecules. Tamarixetin inhibited the phosphorylation of Akt and its downstream signal molecules including IKK and nuclear factor κB. In addition, tamarixetin downregulated the phosphorylation of cytosolic phospholipase A2 (cPLA2) and p38 mitogen-activated protein kinase. Conclusions: Taken together, this study suggests that tamarixetin inhibits degranulation and eicosanoid generation through the PLCγ1 as well as Akt pathways in BMMCs, which would be potential for the prevention of allergic inflammatory diseases (AU)
Subject(s)
Animals , Male , Mice , Hematopoietic Stem Cells/drug effects , Cell Degranulation/drug effects , Disaccharides/pharmacology , Eicosanoids , Quercetin/analogs & derivatives , Inflammation Mediators , Mice, Inbred BALB C , NF-kappa B/metabolism , Phospholipase C gamma/metabolism , Phospholipases A2/metabolism , Phosphorylation/drug effects , Quercetin/pharmacologyABSTRACT
The present study was designed to investigate the clinical. laboratory, and morphological characteristics of the nasal obstruction process. It included 87 patients presenting with polypous rhinosinusitis. The dynamics of the serum leukotriene C4 (LTC4) level in the patients and the morphological changes in their polypous tissue suggested the existence of the pronounced exudative phase of allergic inflammation and provided a basis for the use of the leukotriene receptor antagonist in the form of the sodium montelucast tablets for the treatment of nasal obstruction.
Subject(s)
Acetates , Leukotriene C4/blood , Nasal Obstruction , Nasal Polyps , Quinolines , Rhinitis , Sinusitis , Acetates/pharmacology , Acetates/therapeutic use , Adult , Cyclopropanes , Female , Humans , Inflammation/drug therapy , Inflammation/immunology , Leukotriene Antagonists/pharmacology , Leukotriene Antagonists/therapeutic use , Male , Nasal Obstruction/diagnosis , Nasal Obstruction/drug therapy , Nasal Obstruction/immunology , Nasal Polyps/complications , Nasal Polyps/immunology , Nasal Polyps/pathology , Quinolines/pharmacology , Quinolines/therapeutic use , Rhinitis/complications , Rhinitis/immunology , Sinusitis/complications , Sinusitis/immunology , Sulfides , Treatment OutcomeABSTRACT
BACKGROUND: The ethanol extract of KOTMIN13, composed of Inula japonica Flowers, Trichosanthes kirilowii Semen, Peucedanum praeruptorum Radix, and Allium macrostemon Bulbs, was investigated for its anti-asthmatic and anti-allergic activities. METHODS: The anti-asthmatic effects of KOTMIN13 were evaluated on ovalbumin (OVA)-induced murine asthma model. Anti-allergic properties of KOTMIN13 in bone-marrow derived mast cells (BMMC) and passive cutaneous anaphylaxis (PCA) in vivo were also examined. RESULTS: In asthma model, KOTMIN13 effectively suppressed airway hyperresponsiveness induced by aerosolized methacholine when compared to the levels of OVA-induced mice. KOTMIN13 treatment reduced the total leukocytes, eosinophil percentage, and Th2 cytokines in the bronchoalveolar lavage fluids in OVA-induced mice. The increased levels of eotaxin and Th2 cytokines in the lung as well as serum IgE were decreased by KOTMIN13. The histological analysis shows that the increased inflammatory cell infiltration and mucus secretion were also reduced. In addition, the degranulation and leukotriene C4 production were inhibited in BMMC with IC50 values of 3.9 µg/ml and 1.7 µg/ml, respectively. Furthermore, KOTMIN13 treatment attenuated mast-mediated PCA reaction. CONCLUSIONS: These results demonstrate that KOTMIN13 has anti-asthmatic and anti-allergic effects in vivo and in vitro models.