ABSTRACT
Purpose@#Asthma is a chronic disorder characterized by bronchial hyperresponsiveness and reversible airflow obstruction. Repeated exposure to allergens of the respiratory tract causes chronic inflammation, followed by structural changes in the lung called airway remodeling. House dust mites (HDM) are known as the predominant inhalant allergens, and several studies have reported that the allergenic property of HDM extracts varied with the geographic regions where they were produced. This study aimed to establish a murine experimental model by long-term intranasal exposure to HDM allergen indigenous to Korea. @*Methods@#HDM extracts from cultured Dermatophagoides pteronissunus in Korea were used in our model. We administered the extracts intranasally to BALB/c mice 3 times a week for 8 or 10 consecutive weeks, followed by measuring airway allergic inflammation and airway remodeling. @*Results@#The number of neutrophils in the lungs was higher in the group with long-term exposure to HDM than in the normal control group. The levels of total IgE and a wide range of cytokines, including Th1/Th2/Th17 and proinflammatory cytokines, were significantly higher in the long-term HDM-exposed group than in the normal control group. The development of airway remodeling by chronic exposure to HDM was observed by measuring diverse factors, including collagens and transforming growth factor (TGF)-β. These significant results were more clearly shown in the group exposed to HDM for 8 weeks than 10 weeks. @*Conclusion@#A murine model of chronic exposure to domestic HDM in Korea was successfully established. We suggest that our model may be helpful in the research into asthma with airway remodeling.
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 Cgamma1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-kappaB 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.