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1.
Mol Med Rep ; 16(4): 4201-4207, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28765890

ABSTRACT

Fine particulate matter (PM2.5) has been linked to exacerbation of allergic airway inflammation in mice. However, the mechanism underlying exposure to PM2.5 and subsequent and adverse effects remains to be fully elucidated. Therefore, the present study aimed to investigate the effects of PM2.5 by different levels on airway inflammation in mouse models of in allergic and steroid­resistant asthma. BALB/c mice were nasally instilled with PBS (control) or 10, 31.6 or 100 µg PM2.5, and randomly assigned into nine groups. The acute asthma model was previously induced to investigate the change of inflammatory cells in bronchoalveolar lavage fluid (BALF). Histopathological changes of the lung were assessed, in addition to levels of interleukin (IL)­4 and IL­13 in BALF and immunoglobulin Ein serum. Thymic stromal lymphopoietin (TSLP) proteinexpression levels were assessed by western blotting. The present study demonstrated that medium­ and high­dose PM2.5 is linked to acute exacerbation of allergic airway inflammation in mice. In conclusion, the pathological mechanisms of PM2.5 may be associated with allergic/steroid­resistant airway inflammation, T­cell helper (Th)1/Th2 cytokine production and upregulation of TSLP expression in a murine model of allergic and steroid-resistant asthma.


Subject(s)
Cytokines/metabolism , Hypersensitivity/metabolism , Hypersensitivity/pathology , Particulate Matter/toxicity , Pneumonia/metabolism , Pneumonia/pathology , Animals , Asthma/blood , Asthma/complications , Asthma/pathology , Bronchoalveolar Lavage Fluid , Disease Models, Animal , Female , Hypersensitivity/blood , Hypersensitivity/complications , Immunoglobulin E/blood , Interleukin-13/metabolism , Interleukin-4/metabolism , Lung/pathology , Mice , Mice, Inbred BALB C , Particle Size , Pneumonia/blood , Pneumonia/complications , Thymic Stromal Lymphopoietin
2.
Mol Med Rep ; 12(5): 7693-8, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26502995

ABSTRACT

Asthma is a chronic airway inflammatory disease characterized by an increased mass of airway smooth muscle (ASM). Chrysin (5,7-dihydroxyflavone), a natural flavonoid, has been shown to exert multiple biological activities, including anti-inflammatory, anti-proliferative and anti-oxidant effects, as well as the potency to ameliorate asthma in animal models. The objective of the present study was to identify the underlying mechanism of the therapeutic effects of chrysin. The impact of chrysin on basal and platelet-derived growth factor (PDGF)-induced proliferation and apoptosis of human airway smooth muscle cells (HASMCs) was investigated. Furthermore, the activation of the extracellular signal-regulated protein kinase (ERK) signaling pathway was evaluated in HASMCs. The results revealed that chrysin significantly inhibited basal as well as PDGF-induced HASMC proliferation, most likely through the suppression of ERK1/2 phosphorylation. However, chrysin did not significantly reduce PDGF-induced apoptosis of HASMCs. The present study indicated that chrysin may be a promising medication for controlling airway remodeling and clinical manifestations of asthma.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Cell Proliferation/drug effects , Flavonoids/pharmacology , MAP Kinase Signaling System/drug effects , Myocytes, Smooth Muscle/drug effects , Asthma/drug therapy , Asthma/metabolism , Cell Line , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Myocytes, Smooth Muscle/cytology , Platelet-Derived Growth Factor/metabolism
3.
Zhonghua Yi Xue Za Zhi ; 91(44): 3139-42, 2011 Nov 29.
Article in Chinese | MEDLINE | ID: mdl-22340658

ABSTRACT

OBJECTIVE: To observe the effects of astragaloside IV on the airway remodeling and the expressions of transforming growth factor (TGF)-ß1 and thymic stromal lymphopoietin (TSLP) in a murine model of asthma. METHODS: Forty-eight BALB/c mice were randomly divided into 4 groups, i.e. control group, asthma group, astragaloside IV group and budesonide group (n = 12 each). The BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged with aerosolized OVA for 8 weeks while the mice in the astragaloside IV group were intragastrically administered with astragaloside IV (50 mg/kg) daily for 8 consecutive weeks. Pulmonary functions were measured to evaluate the resistance of expiration. And pulmonary histopathological analysis was performed to observe the infiltration of inflammatory cells, the hyperplasia of airway global cells and the deposition of collagen. The levels of interleukin (IL)-4 and IL-13 in bronchoalveolar lavage fluid (BALF) were measured by ELISA (enzyme linked immunosorbent assay). The pulmonary expression of α-SMA (alpha-smooth muscle actin) was evaluated by immunohistochemistry. The mRNA and protein expressions of TGF-ß1 and TSLP were measured by real-time PCR (polymerase chain reaction) and Western blot respectively. RESULTS: The treatment of astragaloside IV or budesonide led to a sharp decrease in airway resistance compared with the asthma group at a concentration of acetylcholine in 30 µg/kg (P < 0.05). The PAS(+) epithelial/bronchial epithelial cells, the area of collagen staining and α-SMA staining area were significantly elevated in the asthma group compared with the control group (all P < 0.01) while those in the astragaloside and budesonide groups were obviously inhibited compared with the asthma group (all P < 0.05). The BALF levels of IL-4 and IL-13 were markedly elevated in the asthma group versus the control group (P < 0.01) while those markedly decreased in the astragaloside and budesonide groups versus the asthma group (all P < 0.05). The relative expressions of TGF-ß1 and TSLP mRNA (5.23 ± 1.44, 5.70 ± 1.65) were significantly up-regulated in the asthma group versus the control group (1.02 ± 0.21, 1.02 ± 0.25) (P < 0.01) while those in the astragaloside (2.27 ± 0.65, 2.97 ± 1.03) and budesonide groups (2.10 ± 0.57, 3.32 ± 1.11) were obviously down-regulated versus the asthma group (all P < 0.05). The protein levels of TGF-ß1 and TSLP in the asthma group (0.89 ± 0.11, 0.74 ± 0.10) were markedly elevated versus the control (0.39 ± 0.04, 0.44 ± 0.05), the astragaloside (0.51 ± 0.08, 0.59 ± 0.12) and the budesonide groups (0.55 ± 0.08, 0.60 ± 0.08) (all P < 0.05). CONCLUSION: Astragaloside IV can suppress the progression of airway inflammation, airway hyperresponsiveness and remodeling in a murine model of asthma. The above effects may be partially due to the inhibited expressions of TGF-ß1 and TSLP.


Subject(s)
Asthma/metabolism , Cytokines/metabolism , Saponins/pharmacology , Transforming Growth Factor beta1/metabolism , Triterpenes/pharmacology , Animals , Asthma/pathology , Drugs, Chinese Herbal/pharmacology , Female , Interleukin-13/metabolism , Interleukin-4/metabolism , Mice , Mice, Inbred BALB C , Thymic Stromal Lymphopoietin
4.
Can J Physiol Pharmacol ; 88(10): 1010-6, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20962901

ABSTRACT

Paeonol, the main active component isolated from Moutan Cortex, possesses extensive pharmacological activities such as anti-inflammatory, anti-allergic, and immunoregulatory effects. In the present study, we examined the effects of paeonol on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice sensitized and challenged with ovalbumin were administered paeonol intragastrically at a dose of 100 mg/kg daily. Paeonol significantly suppressed ovalbumin-induced airway hyperresponsiveness to acetylcholine chloride. Paeonol administration significantly inhibited the total inflammatory cell and eosinophil count in bronchoalveolar lavage fluid. Treatment with paeonol significantly enhanced IFN-γ levels and decreased interleukin-4 and interleukin-13 levels in bronchoalveolar lavage fluid and total immunoglobulin E levels in serum. Histological examination of lung tissue demonstrated that paeonol significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. These data suggest that paeonol exhibits anti-inflammatory activity in allergic mice and may possess new therapeutic potential for the treatment of allergic bronchial asthma.


Subject(s)
Acetophenones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Asthma/drug therapy , Pneumonia/drug therapy , Acetophenones/administration & dosage , Airway Resistance/drug effects , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Asthma/blood , Asthma/immunology , Asthma/pathology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Cytokines/blood , Cytokines/immunology , Disease Models, Animal , Female , Immunoglobulin E/blood , Immunoglobulin E/immunology , Mice , Mice, Inbred BALB C , Ovalbumin/immunology , Plethysmography, Whole Body , Pneumonia/blood , Pneumonia/immunology , Pneumonia/pathology
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