scholarly journals Simvastatin inhibits goblet cell hyperplasia and lung arginase in a mouse model of allergic asthma: a novel treatment for airway remodeling?

2010 ◽  
Vol 156 (6) ◽  
pp. 335-349 ◽  
Author(s):  
Amir A. Zeki ◽  
Jennifer M. Bratt ◽  
Michelle Rabowsky ◽  
Jerold A. Last ◽  
Nicholas J. Kenyon
Author(s):  
Linlin Feng ◽  
Tingting Meng ◽  
Yunyun Qi ◽  
Seyyed Shamsadin Athari ◽  
Xiaoyun Chen

  Allergic asthma is a complicated respiratory problem characterized by airway inflammation, airway hyperresponsiveness (AHR), breathlessness, mucus hyper-secretion, and goblet cell hyperplasia. Asthma is controlled by genetic and environmental factors. Allergy is the main trigger of asthma and is mediated by Th2 cytokines along with IgE production. Vitamin D (Vit D) is the main supplementary factor for the immune system. In the present study, we investigated the effect of Vit D on the exacerbation of allergic asthma. A murine model of allergic asthma was induced by ovalbumin (OVA) in four of five groups of studied female BALB/c mice (each group, n=20). One group was considered as control. Of OVA-induced mice, two groups received Vit D via oral (10,000 IU/kg diet) or intranasal (inhalation) forms (30 min on days 25, 27, and 29), and the third group received budesonide. At least, AHR, the levels of IL-4, IL-5, IL-13, and INF-g in bronchoalveolar lavage fluid (BALF), serum IgE and histamine, IL-25 and IL-33 gene expression, as well as histopathology study of the lung were done. The Penh values, type2 Cytokines in BALF (in both protein and molecular levels), total IgE and histamine, perivascular and peribronchial inflammation, goblet cell hyperplasia, and mucus hypersecretion decreased significantly in both oral and intranasal Vit D-treated asthmatic mice groups, especially on day 38 of orally treated mice. Here, we found Vit D as a promising agent in control of allergic asthma with a remarkable ability to decrease the severity of inflammation. Therefore, Vit D sufficiency is highly recommended in asthmatic patients.


2010 ◽  
Vol 59 (3) ◽  
pp. 313-319 ◽  
Author(s):  
Yuhui Ouyang ◽  
Masanori Miyata ◽  
Kyosuke Hatsushika ◽  
Yuko Ohnuma ◽  
Ryohei Katoh ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Chau Ling Tham ◽  
Sin Yee Yeoh ◽  
Chun Hao Ong ◽  
Hanis Hazeera Harith ◽  
Daud Ahmad Israf

2,6-Bis-(4-hydroxyl-3-methoxybenzylidine) cyclohexanone (BHMC), a synthetic curcuminoid analogue, has been shown to exhibit anti-inflammatory properties in cellular models of inflammation and improve the survival of mice from lethal sepsis. We further evaluated the therapeutic effect of BHMC on acute airway inflammation in a mouse model of allergic asthma. Mice were sensitized and challenged with ovalbumin (OVA), followed by intraperitoneal administration of 0.1, 1, and 10 mg/kg of BHMC. Bronchoalveolar lavage fluid, blood, and lung samples were collected, and the respiratory function was measured. OVA sensitization and challenge increased airway hyperresponsiveness (AHR) and pulmonary inflammation. All three doses of BHMC (0.1-10 mg/kg) significantly reduced the number of eosinophils, lymphocytes, macrophages, and neutrophils, as well as the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) as compared to OVA­challenged mice. However, serum level of IgE was not affected. All three doses of BHMC (0.1-10 mg/kg) were effective in suppressing the infiltration of inflammatory cells at the peribronchial and perivascular regions, with the greatest effect observed at 1 mg/kg which was comparable to dexamethasone. Goblet cell hyperplasia was inhibited by 1 and 10 mg/kg of BHMC, while the lowest dose (0.1 mg/kg) had no significant inhibitory effect. These findings demonstrate that BHMC, a synthetic nonsteroidal small molecule, ameliorates acute airway inflammation associated with allergic asthma, primarily by suppressing the release of inflammatory mediators and goblet cell hyperplasia to a lesser extent in acute airway inflammation of allergic asthma.


2017 ◽  
Vol 131 (11) ◽  
pp. 955-960 ◽  
Author(s):  
H Yu ◽  
H Sun ◽  
Z Wang ◽  
Y Liu

AbstractObjective:To investigate the effect of microRNA let-7a on OPN expression in a mouse model of allergic rhinitis.Methods:Thirty-two mature female C57BL/6 mice were randomly divided into four groups, with eight mice in each group: microRNA let-7a, microRNA control, OVA and phosphate-buffered saline groups. The microRNA let-7a, microRNA control and OVA groups were sensitised with OVA to establish a mouse model of allergic rhinitis. Nose-scratching events were counted. Nasal mucosa was used to evaluate histological changes of goblet cell hyperplasia. Interleukins 5 and 13 were detected. Interferon-γ levels in the nasal lavage fluid were assayed with enzyme-linked immunosorbent assay. OPN expression was estimated with polymerase chain reaction.Results:Compared with microRNA control mice, microRNA let-7a treated mice had a significantly increased number of nose-scratching events, nasal mucosal eosinophilia and goblet cell hyperplasia (p < 0.05), and significantly higher interleukins 5 and 13 in nasal mucosa (p < 0.05), but there was no significant difference in interferon-γ (p > 0.05). In addition, microRNA let-7a treated mice had significantly enhanced OPN expression in nasal mucosa (p < 0.05).Conclusion:MicroRNA let-7a can promote allergic rhinitis development partly by regulating OPN expression.


2012 ◽  
Vol 26 (6) ◽  
pp. 421-427
Author(s):  
Young-Jun Chung ◽  
Hyo Yeol Kim ◽  
Seung-Kyu Chung ◽  
Hun-Jong Dhong

Background Only a few studies have investigated the airway remodeling process in allergic rhinitis (AR), and the results reported are conflicting. We established an allergen-induced nasal remodeling model for AR using brown Norway rats and investigated time-dependent histological changes and the reversibility of the epithelial and subepithelial changes. Methods Ovalbumin (OVA)-sensitized rats were exposed to OVA daily and then assigned to one of five groups depending on the duration of the challenge. Groups I, II, III, and IV rats were exposed for 1, 4, 8, and 12 weeks, respectively. Group V rats were exposed for 12 weeks and then protected from challenge for 4 weeks. Matched control rats were exposed to saline. Histological parameters of the nasal mucosa such as epithelial and subepithelial thickness, goblet cell hyperplasia, eosinophil infiltration, submucosal gland hypertrophy, and expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were compared between groups. Results Repeated challenges for 12 weeks resulted in the characteristic features of nasal airway remodeling. All parameters except epithelial thickness increased markedly. Goblet cell hyperplasia and eosinophil infiltration decreased to control group levels after cessation of challenge for 4 weeks. Subepithelial changes such as subepithelial thickening, submucosal gland hypertrophy, and increased expression of MMP-9 and TIMP-1 were still observed after 4 weeks without challenge. Conclusion Our results indicate that prolonged OVA challenge can induce nasal remodeling. Epithelial changes were minimal or absent after cessation of the challenge, but subepithelial changes were resistant to reversal.


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